Multidisciplinary Approaches to Manage COVID-19: From Surveillance to Diagnosis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Point-of-Care Diagnostics and Devices".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 73912

Special Issue Editor

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic emergency can hardly be managed with standard approaches. For a prompt return to previous levels of social interaction and business, virus diffusion must be curbed and kept under control—this requires a robust surveillance strategy, for which virus testing will be central. Diagnostic screening should be performed at a mass scale, extended to the asymptomatic population, and repeated over time. Different types of diagnostic tests are now available with alternative methods and benefits. As monitoring capacity is limited, there is a strong necessity for new strategies that could massively increase laboratory efficiency while maintaining the benefit of time- and cost-effectiveness.

The effectiveness of diagnostic tests should not be evaluated as a standalone but in the context of a prolonged surveillance strategy where the necessity of analytical sensitivity must come to terms with the need for a short turnaround time and high testing frequency.

This Special Issue aims to focus attention on the increasing need for multidisciplinary approaches in which diagnostic, clinical, epidemiological, and statistical concerns and insights synergically come together to develop new efficient surveillance strategies, tailored to the characteristics of different monitoring contexts.

Prof. Dr. Alessandro Russo
Guest Editor

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Keywords

  • COVID-19
  • Surveillance strategies
  • Molecular testing
  • Antigenic testing
  • Rapid test
  • Self-administration test
  • Group testing
  • Efficiency evaluations

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Published Papers (54 papers)

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13 pages, 704 KiB  
Article
RT-LAMP Multicenter Study for SARS-CoV-2 Genome Molecular Detection in Brazilian Swab and Saliva Samples
by Vanessa Duarte da Costa, Alanna Calheiros Santos, Lucas Lima da Silva, Wilian Jean Wiggers, Claudia Alexandra Pontes Ivantes, Danielle Malta Lima, Jeová Keny Baima Colares, Deusilene Souza Vieira Dallacqua, Ana Rita Coimbra Motta-Castro, Alberto Martín Rivera Dávila, Sheila Araujo Teles, Megmar Aparecida dos Santos Carneiro, Karlla Antonieta Amorim Caetano, Fernando Antonio Costa Anunciação, Vanessa Salete de Paula, Livia Melo Villar and on behalf of The Brazilian COVID-19 Research Group
Diagnostics 2023, 13(2), 210; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13020210 - 06 Jan 2023
Cited by 1 | Viewed by 1570
Abstract
Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a rapid method that can replace RT-qPCR. A simple molecular assay for SARS-CoV-2 RNA detection in gold-standard diagnosis through swabs and alternative specimens such as saliva could be helpful in promoting genomic surveillance. A multicenter study [...] Read more.
Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a rapid method that can replace RT-qPCR. A simple molecular assay for SARS-CoV-2 RNA detection in gold-standard diagnosis through swabs and alternative specimens such as saliva could be helpful in promoting genomic surveillance. A multicenter study was conducted to evaluate the RT-LAMP assay method as an alternative for the molecular detection of SARS-CoV-2 lineages in swab and saliva samples. A total of 350 swabs from individuals with (n = 276) or without (n = 74) COVID-19 tested by RT-qPCR were collected. Paired saliva was also collected from 90 individuals who had SARS-CoV-2 RNA that was detectable (n = 30) or undetectable (n = 60) via RT-qPCR. For the RT-LAMP methodology, six primers were used for ORF1 gene amplification. As for SARS-CoV-2 genotyping, 39 swabs had the whole genome sequenced by MinION. The sensitivity of RT-LAMP to the swab was 90.2%. For the swab samples with Ct ≤ 30, the sensitivity improved by 96%. Considering saliva with Ct ≤ 30 in RT-qPCR testing, the RT-LAMP sensitivity was 100%. The RT-LAMP specificity was 100% for both the swab and saliva samples. This RT-LAMP assay was capable of detecting all the SARS-CoV-2 lineages circulating in the Brazilian swab samples. The RT-LAMP method has significant potential for use in clinical routines since it was capable of detecting SARS-CoV-2 RNA in swab and saliva samples. Full article
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12 pages, 311 KiB  
Article
Content of Essential Trace Elements in the Hair of Residents of the Caspian Region of the Republic of Kazakhstan Who Recovered from COVID-19
by Gulnara Batyrova, Zhenisgul Tlegenova, Victoria Kononets, Gulmira Umarova, Yerlan Bazargaliyev, Gulaim Taskozhina, Nurgul Kereyeva and Yeskendir Umarov
Diagnostics 2022, 12(11), 2734; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112734 - 08 Nov 2022
Cited by 2 | Viewed by 1053
Abstract
This study aimed to investigate the content of essential elements in the hair of unvaccinated residents of the Caspian region who recovered from COVID-19. This cross-sectional study involved 260 unvaccinated permanent residents of Mangistau oblast aged 18–60. The diagnosis and severity of COVID-19 [...] Read more.
This study aimed to investigate the content of essential elements in the hair of unvaccinated residents of the Caspian region who recovered from COVID-19. This cross-sectional study involved 260 unvaccinated permanent residents of Mangistau oblast aged 18–60. The diagnosis and severity of COVID-19 were based on clinical signs and symptoms, laboratory data, R-graph results, and oxygen saturation by the Clinical Protocol of the Ministry of Health of the Republic of Kazakhstan. Inductively coupled plasma mass spectrometry determined the content of trace elements cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), iodine (I), manganese (Mn), selenium (Se), and zinc (Zn). The content of Cr (p < 0.05), Cu (p < 0.05), Fe (p < 0.001), I (p < 0.05), Mn (p < 0.001), and Zn (p < 0.05) in the hair of individuals who had a coronavirus infection was lower than those who did not have this infection. There were significantly higher levels of Cu (p < 0.05) in the hair of participants who had moderate or severe COVID-19 compared to those with mild forms. The results of multiple regression analysis showed that in the presence of a COVID-19 infection in a subject’s history, the content of Cr (0.871 (95% CI: 0.811; 0.936)), Cu (0.875 (95% CI: 0.803; 0.955)), Fe (0.745 (95% CI: 0.636; 0.873)), and Mn (0.642 (95%CI: 00.518; 0.795)) decreased in the hair. The data obtained indicate that past COVID-19 infections affect the trace element status of the inhabitants of the Caspian region of Kazakhstan. Full article
9 pages, 879 KiB  
Communication
Evaluation of Hepcidin Level in COVID-19 Patients Admitted to the Intensive Care Unit
by Marco Ciotti, Marzia Nuccetelli, Massimo Pieri, Carlo Maria Petrangeli, Alfredo Giovannelli, Terenzio Cosio, Luigi Rosa, Piera Valenti, Francesca Leonardis, Jacopo Maria Legramante, Sergio Bernardini, Elena Campione and Marilena Minieri
Diagnostics 2022, 12(11), 2665; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112665 - 02 Nov 2022
Cited by 2 | Viewed by 1259
Abstract
Coronavirus disease 2019 (COVID-19) presents a clinical spectrum that ranges from a mild condition to critical illness. Patients with critical illness present respiratory failure, septic shock and/or multi-organ failure induced by the so called “cytokine storm”. Inflammatory cytokines affect iron metabolism, mainly inducing [...] Read more.
Coronavirus disease 2019 (COVID-19) presents a clinical spectrum that ranges from a mild condition to critical illness. Patients with critical illness present respiratory failure, septic shock and/or multi-organ failure induced by the so called “cytokine storm”. Inflammatory cytokines affect iron metabolism, mainly inducing the synthesis of hepcidin, a hormone peptide not routinely measured. High levels of hepcidin have been associated with the severity of COVID-19. The aim of this study was to analyze, retrospectively, the levels of hepcidin in a group of COVID-19 patients admitted to the intensive care unit (ICU) of the Policlinico Tor Vergata of Rome, Italy. Thirty-eight patients from November 2020 to May 2021 were enrolled in the study. Based on the clinical outcome, the patients were assigned to two groups: survivors and non-survivors. Moreover, a series of routine laboratory parameters were monitored during the stay of the patients in the ICU and their levels correlated to the outcome. Statistical differences in the level of hepcidin, D-dimer, IL-6, LDH, NLR, neutrophils level, CRP, TNF-α and transferrin were observed between the groups. In particular, hepcidin values showed significantly different median concentrations (88 ng/mL vs. 146 ng/mL) between survivors and non-survivors. In addition, ROC curves analysis revealed sensitivity and specificity values of 74% and 76%, respectively, at a cut-off of 127 (ng/mL), indicating hepcidin as a good biomarker in predicting the severity and mortality of COVID-19 in ICU patients. Full article
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24 pages, 1772 KiB  
Article
EVAE-Net: An Ensemble Variational Autoencoder Deep Learning Network for COVID-19 Classification Based on Chest X-ray Images
by Daniel Addo, Shijie Zhou, Jehoiada Kofi Jackson, Grace Ugochi Nneji, Happy Nkanta Monday, Kwabena Sarpong, Rutherford Agbeshi Patamia, Favour Ekong and Christyn Akosua Owusu-Agyei
Diagnostics 2022, 12(11), 2569; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112569 - 22 Oct 2022
Cited by 7 | Viewed by 3084
Abstract
The COVID-19 pandemic has had a significant impact on many lives and the economies of many countries since late December 2019. Early detection with high accuracy is essential to help break the chain of transmission. Several radiological methodologies, such as CT scan and [...] Read more.
The COVID-19 pandemic has had a significant impact on many lives and the economies of many countries since late December 2019. Early detection with high accuracy is essential to help break the chain of transmission. Several radiological methodologies, such as CT scan and chest X-ray, have been employed in diagnosing and monitoring COVID-19 disease. Still, these methodologies are time-consuming and require trial and error. Machine learning techniques are currently being applied by several studies to deal with COVID-19. This study exploits the latent embeddings of variational autoencoders combined with ensemble techniques to propose three effective EVAE-Net models to detect COVID-19 disease. Two encoders are trained on chest X-ray images to generate two feature maps. The feature maps are concatenated and passed to either a combined or individual reparameterization phase to generate latent embeddings by sampling from a distribution. The latent embeddings are concatenated and passed to a classification head for classification. The COVID-19 Radiography Dataset from Kaggle is the source of chest X-ray images. The performances of the three models are evaluated. The proposed model shows satisfactory performance, with the best model achieving 99.19% and 98.66% accuracy on four classes and three classes, respectively. Full article
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11 pages, 2368 KiB  
Article
SARS-CoV-2 IgG Levels Allow Predicting the Optimal Time Span of Convalescent Plasma Donor Suitability
by Sandra Laner-Plamberger, Nadja Lindlbauer, Lisa Weidner, Simon Gänsdorfer, Lukas Weseslindtner, Nina Held, Wanda Lauth, Georg Zimmermann, Jan Marco Kern, Fabian Föttinger, Laura Ombres, Christof Jungbauer, Eva Rohde and Christoph Grabmer
Diagnostics 2022, 12(11), 2567; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12112567 - 22 Oct 2022
Viewed by 1019
Abstract
Convalescent plasma (CP) has been in use for the treatment of numerous infectious diseases for more than a century, recently also for coronavirus disease 2019 (COVID-19). A major challenge for this treatment is identifying suitable donors with sufficient levels of functional antibodies and [...] Read more.
Convalescent plasma (CP) has been in use for the treatment of numerous infectious diseases for more than a century, recently also for coronavirus disease 2019 (COVID-19). A major challenge for this treatment is identifying suitable donors with sufficient levels of functional antibodies and to determine the optimal time span for CP donation. In this retrospective study, we analyzed 189 CP donations of 66 donors regarding anti-SARS-CoV-2 anti-S IgG antibody levels. We found a significant correlation between the semi-quantitative SARS-CoV-2 IgG ratio values and in vitro antibody functionality. A time-to-event analysis allowed us to predict the optimal time span of COVID-19 CP donor suitability. We found that high IgG ratio values, which significantly correlate with high in vitro antibody functionality, were suitable for CP donation for a median of 134 days after the first CP donation. Donors with lower IgG ratios were suitable for a median of 53 days. Our data support plasma collection centers to determine optimal points in time for CP donation by means of widely used semi-quantitative laboratory IgG ratio values. Full article
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17 pages, 1422 KiB  
Article
Distribution of Pathogens and Predictive Values of Biomarkers of Inflammatory Response at ICU Admission on Outcomes of Critically Ill COVID-19 Patients with Bacterial Superinfections—Observations from National COVID-19 Hospital in Croatia
by Maja Ćurčić, Marko Tarle, Hani Almahariq, Sonja Hleb, Juraj Havaš, Marko Pražetina, Hrvoje Lasić, Emil Dolenc, Andrea Kukoč, Antonija Mihelčić, Ivan Miko, Andrea Romić, Danijela Tipura, Željka Drmić, Marcela Čučković, Vanja Blagaj, Ivica Lukšić, Jasminka Peršec and Andrej Šribar
Diagnostics 2022, 12(9), 2069; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12092069 - 26 Aug 2022
Cited by 3 | Viewed by 1463
Abstract
Background: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream [...] Read more.
Background: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. Methods: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. Results: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. Conclusion: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI. Full article
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16 pages, 7441 KiB  
Article
Interstitial Lung Fibrosis Following COVID-19 Pneumonia
by Mihai Lazar, Ecaterina Constanta Barbu, Cristina Emilia Chitu, Catalin Tiliscan, Laurentiu Stratan, Sorin Stefan Arama, Victoria Arama and Daniela Adriana Ion
Diagnostics 2022, 12(8), 2028; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12082028 - 22 Aug 2022
Cited by 10 | Viewed by 2714
Abstract
Background and Objectives: Pulmonary fibrosis represents a stage of normal physiologic response to inflammatory aggression, mostly self-limiting and reversible; however, numerous patients treated for SARS-CoV-2 pneumonia present after release from hospital residual lung fibrosis. In this article, we aim to present an optimization [...] Read more.
Background and Objectives: Pulmonary fibrosis represents a stage of normal physiologic response to inflammatory aggression, mostly self-limiting and reversible; however, numerous patients treated for SARS-CoV-2 pneumonia present after release from hospital residual lung fibrosis. In this article, we aim to present an optimization method for evaluating pulmonary fibrosis by quantitative analysis, to identify the risk factors/predictors for pulmonary fibrosis in patients with SARS-CoV-2 infection, and to characterize the impact of pulmonary fibrosis on the symptomatology of patients after release from the hospital. Materials and Methods: We performed a prospective observational study on 100 patients with severe forms of pneumonia, with a control group of 61 non-COVID normal patients. Results: We found persistent interstitial changes consistent with fibrotic changes in 69% of patients. The risk of fibrosis was proportional to the values of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and lactate dehydrogenase (LDH), and to the duration of hospitalization. The imaging parameters correlated with increased risk for interstitial fibrosis were the number of affected pulmonary lobes and the percent of interstitial pulmonary fibrosis. Conclusions: The main risk factors for pulmonary fibrosis post-COVID-19 identified in our study are increased ESR, CRP, LDH, duration of hospitalization and the severity of pneumonia. Full article
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13 pages, 2192 KiB  
Article
Isolated Severe Dysphonia as a Presentation of Post-COVID-19 Syndrome
by Joanna Jeleniewska, Ewa Niebudek-Bogusz, Jakub Malinowski, Joanna Morawska, Joanna Miłkowska-Dymanowska and Wioletta Pietruszewska
Diagnostics 2022, 12(8), 1839; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12081839 - 29 Jul 2022
Cited by 3 | Viewed by 2838
Abstract
This is the first study assessing the clinical management of severe, isolated dysphonia during post-COVID-19 syndrome. One hundred and fifty-eight subjects met the inclusion criteria for the post-COVID-19 condition as specified by the WHO. Six patients were diagnosed with isolated severe dysphonia, constituting [...] Read more.
This is the first study assessing the clinical management of severe, isolated dysphonia during post-COVID-19 syndrome. One hundred and fifty-eight subjects met the inclusion criteria for the post-COVID-19 condition as specified by the WHO. Six patients were diagnosed with isolated severe dysphonia, constituting 3.8% of the initial group. The pre- and post-examination protocol consisted of subjective voice self-assessment and routine laryngological examination, followed by an instrumental examination by means of Laryngovideostroboscopy (LVS) and High-Speed Videolaryngoscopy (HSV). The treatment included short-term systemic steroids in decreasing doses, moisturizing inhalations with hyaluronic acid, and protective agents against Laryngopharyngeal Reflux. The kinematic imaging of the glottis performed by means of HSV before treatment showed deviations in the regularity and symmetry of vocal fold vibrations, absence of mucosal wave, and incomplete glottal closure. Improvement of the structural and functional state of the larynx was observed post-treatment. Kymographic sections and Glottal Width Waveform (GWW) graphs obtained from post-treatment HSV recordings showed improvement in vocal fold vibrations. The decrease in mean Jitter and Shimmer was observed, with the following mean values of 3.16 pre-treatment and 2.97 post-treatment for Jitter and 7.16 pre-treatment and 2.77 post-treatment for Shimmer. The post-treatment self-evaluation of voice showed considerable improvement in vocal function and voice quality in all the examined patients. Severe dysphonia in patients with post-COVID-19 syndrome requires urgent ENT diagnosis using instrumental assessment with the evaluation of laryngeal phonatory function and intensive comprehensive treatment. Full article
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12 pages, 1004 KiB  
Article
Decreased Levels of SARS-CoV-2 Fusion-Inhibitory Antibodies in the Serum of Aged COVID-19 Patients
by Astrid Malézieux-Picard, Fabien Abdul, François R. Herrmann, Aurélie Caillon, Pascale Ribaux, Yves Cambet, Sabine Yerly, Stéphanie Baggio, Nathalie Vernaz, Dina Zekry, Karl-Heinz Krause, Olivier Preynat-Seauve and Virginie Prendki
Diagnostics 2022, 12(8), 1813; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12081813 - 28 Jul 2022
Viewed by 1379
Abstract
Background: The SARS-CoV-2 pandemic was particularly devastating for elderly people, and the underlying mechanisms of the disease are still poorly understood. In this study, we investigated fusion inhibitory antibodies (fiAbs) in elderly and younger COVID-19 patients and analyzed predictive factors for their occurrence. [...] Read more.
Background: The SARS-CoV-2 pandemic was particularly devastating for elderly people, and the underlying mechanisms of the disease are still poorly understood. In this study, we investigated fusion inhibitory antibodies (fiAbs) in elderly and younger COVID-19 patients and analyzed predictive factors for their occurrence. Methods: Data and samples were collected in two cohorts of hospitalized patients. A fusion assay of SARS-CoV-2 spike-expressing cells with ACE2-expressing cells was used to quantify fiAbs in the serum of patients. Results: A total of 108 patients (52 elderly (mean age 85 ± 7 years); 56 young (mean age 52 ± 10 years)) were studied. The concentrations of fiAbs were lower in geriatric patients, as evidenced at high serum dilutions (1/512). The association between fiAbs and anti-Spike Ig levels was weak (correlation coefficient < 0.3), but statistically significant. Variables associated with fusion were the delay between the onset of symptoms and testing (HR = −2.69; p < 0.001), clinical frailty scale (HR = 4.71; p = 0.035), and WHO severity score (HR = −6.01, p = 0.048). Conclusions: Elderly patients had lower fiAbs levels after COVID-19 infection. The decreased fiAbs levels were associated with frailty. Full article
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10 pages, 1022 KiB  
Article
The Matrix Effect in the RT-PCR Detection of SARS-CoV-2 Using Saliva without RNA Extraction
by Orlando Morais, Manuel Rui Alves, Carla Ramos, Fernando Ferreira and Paulo Fernandes
Diagnostics 2022, 12(7), 1547; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12071547 - 25 Jun 2022
Cited by 7 | Viewed by 1269
Abstract
The present work focuses on the detection of SARS-CoV-2 in saliva, contributing to understanding the inhibition effect of the matrix and its influence on the results. Detection of viral genes ORF1ab, N, and E was performed by RT-PCR using saliva directly in the [...] Read more.
The present work focuses on the detection of SARS-CoV-2 in saliva, contributing to understanding the inhibition effect of the matrix and its influence on the results. Detection of viral genes ORF1ab, N, and E was performed by RT-PCR using saliva directly in the reaction without RNA extraction. Different amounts of saliva were spiked with increasing amounts of viral RNA from COVID-19 patients and subjected to RT-PCR detection. In parallel, 64 saliva samples from confirmed COVID-19 patients were used in two different amounts directly in the RT-PCR reaction and their results compared. The presence of saliva in the RT-PCR always causes a positive shift of the Ct values, but a very high between-person variability of its magnitude was obtained, with increases ranging from 0.93 to 11.36. Viral targets are also affected differently depending on the initial number of viral particles. Due to inhibitors present in saliva, the duplication of sample volume causes only 48 to 61% of the expected Ct value decrease depending on the viral target gene. The use of saliva has advantages, but also limitations, due to potential inhibitors present in the matrix. However, the choice of the target and the right amount of sample may significantly influence the results. Full article
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9 pages, 967 KiB  
Article
Comparison of Four Systems for SARS-CoV-2 Antibody at Three Time Points after SARS-CoV-2 Vaccination
by Jong Do Seo, Minjeong Nam, Tae Hwan Lee, Yeon-Sun Ahn, Seon-Hyeon Shin, Hye Young Han and Hee-Won Moon
Diagnostics 2022, 12(6), 1349; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12061349 - 29 May 2022
Viewed by 1415
Abstract
Background: Immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes over time after vaccination. Methods: We compared SARS-CoV-2 antibody levels in serial samples from 350 vaccinated individuals at 3 time points (3 weeks after the first or second dose and before the [...] Read more.
Background: Immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes over time after vaccination. Methods: We compared SARS-CoV-2 antibody levels in serial samples from 350 vaccinated individuals at 3 time points (3 weeks after the first or second dose and before the third dose) with 4 assays: GenScript cPASS SARS-CoV-2 neutralization antibody detection kits (cPASS), Siemens SARS-CoV-2 IgG (sCOVG), Abbott SARS-CoV-2 IgG II Quant (CoV-2 IgG II), and an Immuno-On™ COVID-19 IgG test (Immuno-On IgG). Antibody levels by time, concordance between assays, and values from other tests corresponding to the percent inhibition results in cPASS were assessed. Results: The median values at three time points were 49.31%, 90.87%, and 53.38% inhibition for cPASS, 5.39, 13.65, and 2.24 U/mL for sCOVG, 570.25, 1279.65, and 315.80 AU/mL for CoV-2 IgG II, and 223.22, 362.20, and 62.20 relative units (RU) for Immuno-On IgG. The concordance with cPASS at each time point ranged from 0.735 to 0.984, showing the highest concordance in the second sample and lowest concordance in the third in all comparative tests. The values corresponded to 30% inhibition, and the cutoffs of cPASS, were 2.02 U/mL, 258.6 AU/mL, and 74.2 RU for each test. Those for 50%, 70%, and 90% inhibition were 3.16, 5.66, and 8.26 U/mL for sCOVG, while they were 412.5, 596.9, and 1121.6 AU/mL for CoV-2 IgG II and 141.8, 248.92, and 327.14 RU for Immuno-On IgG. Conclusions: This study demonstrated the dynamic changes in antibody values at different time points using four test systems and is expected to provide useful baseline data for comparative studies and standardization efforts in the future. Full article
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9 pages, 992 KiB  
Article
SARS-CoV-2 Antigen Test Results to Infer Active or Non-Active Virus Replication Status in COVID-19 Patients
by Giulia De Angelis, Giulia Menchinelli, Flora Marzia Liotti, Simona Marchetti, Alessandro Salustri, Antonietta Vella, Rosaria Santangelo, Brunella Posteraro and Maurizio Sanguinetti
Diagnostics 2022, 12(6), 1338; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12061338 - 28 May 2022
Cited by 3 | Viewed by 1672
Abstract
We used nasopharyngeal swab samples of patients with a symptomatic (n = 82) or asymptomatic (n = 20) coronavirus disease 2019 (COVID-19) diagnosis to assess the ability of antigen detection tests to infer active (potentially transmissible) or inactive (potentially non-transmissible) infection by severe [...] Read more.
We used nasopharyngeal swab samples of patients with a symptomatic (n = 82) or asymptomatic (n = 20) coronavirus disease 2019 (COVID-19) diagnosis to assess the ability of antigen detection tests to infer active (potentially transmissible) or inactive (potentially non-transmissible) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the subgenomic RNA (sgRNA) as an active replication marker of SARS-CoV-2, 48 (76.2%), 56 (88.9%), and 63 (100%) of 63 samples with sgRNA positive results tested positive with the SD BIOSENSOR STANDARD Q COVID-19 Ag (Standard Q), the SD BIOSENSOR STANDARD F COVID-19 Ag FIA (Standard F), or the Fujirebio LUMIPULSE G SARS-CoV-2 Ag (Lumipulse) assay, respectively. Conversely, 37 (94.9%), 29 (74.4%), and 7 (17.9%) of 39 samples with sgRNA negative results tested negative with Standard Q, Standard F, or Lumipulse, respectively. Stratifying results by the number of days of symptoms before testing revealed that most antigen positive/sgRNA positive results were among samples tested at 2–7 days regardless of the assay used. Conversely, most antigen negative/sgRNA negative results were among samples tested at 16–30 days only when Standard Q or Standard F were used. In conclusion, based on our findings, a negative antigen test, especially with the Lumipulse assay, or a positive antigen test, especially with the Standard F assay, may suggest, respectively, the absence or presence of replication-competent SARS-CoV-2. Full article
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16 pages, 53587 KiB  
Article
The Coronavirus Disease 2019 Spatial Care Path: Home, Community, and Emergency Diagnostic Portals
by Gerald J. Kost
Diagnostics 2022, 12(5), 1216; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12051216 - 12 May 2022
Cited by 4 | Viewed by 1544
Abstract
This research uses mathematically derived visual logistics to interpret COVID-19 molecular and rapid antigen test (RAgT) performance, determine prevalence boundaries where risk exceeds expectations, and evaluate benefits of recursive testing along home, community, and emergency spatial care paths. Mathematica and open access software [...] Read more.
This research uses mathematically derived visual logistics to interpret COVID-19 molecular and rapid antigen test (RAgT) performance, determine prevalence boundaries where risk exceeds expectations, and evaluate benefits of recursive testing along home, community, and emergency spatial care paths. Mathematica and open access software helped graph relationships, compare performance patterns, and perform recursive computations. Tiered sensitivity/specificity comprise: (T1) 90%/95%; (T2) 95%/97.5%; and (T3) 100%/≥99%, respectively. In emergency medicine, median RAgT performance peaks at 13.2% prevalence, then falls below T1, generating risky prevalence boundaries. RAgTs in pediatric ERs/EDs parallel this pattern with asymptomatic worse than symptomatic performance. In communities, RAgTs display large uncertainty with median prevalence boundary of 14.8% for 1/20 missed diagnoses, and at prevalence > 33.3–36.9% risk 10% false omissions for symptomatic subjects. Recursive testing improves home RAgT performance. Home molecular tests elevate performance above T1 but lack adequate validation. Widespread RAgT availability encourages self-testing. Asymptomatic RAgT and PCR-based saliva testing present the highest chance of missed diagnoses. Home testing twice, once just before mingling, and molecular-based self-testing, help avoid false omissions. Community and ER/ED RAgTs can identify contagiousness in low prevalence. Real-world trials of performance, cost-effectiveness, and public health impact could identify home molecular diagnostics as an optimal diagnostic portal. Full article
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9 pages, 622 KiB  
Article
Validation of GeneFinder COVID-19 Ag Plus Rapid Test and Its Potential Utility to Slowing Infection Waves: A Single-Center Laboratory Evaluation Study
by Cinzia Peronace, Rossana Tallerico, Manuela Colosimo, Vanessa Sacco, Roberta Talarico, Marco De Fazio, Federica Pasceri, Ilenia Talotta, Giuseppina Panduri, Jung-Hee Kim, Erika Cione and Pasquale Minchella
Diagnostics 2022, 12(5), 1126; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12051126 - 01 May 2022
Cited by 3 | Viewed by 2428
Abstract
Diagnostic laboratory tools are essential to keep everyone safe and track newly emerging variants; on the other hand, “filter” screening tests recognizing positivity are valuable tools to avoid hectic laboratory work that, besides COVID-19, are also part of the routine. Therefore, complementary assays, [...] Read more.
Diagnostic laboratory tools are essential to keep everyone safe and track newly emerging variants; on the other hand, “filter” screening tests recognizing positivity are valuable tools to avoid hectic laboratory work that, besides COVID-19, are also part of the routine. Therefore, complementary assays, such as rapid antigen tests (RATs), are essential in controlling and monitoring virus spread within the community, especially in the asymptomatic population. A subset of nasopharyngeal swab specimens resulted in SARS-CoV-2 positive and investigated for genomic characterization were used for RAT validation. RATs were performed immediately after sampling, following the manufacturer’s instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimens’ collection. Out of 603 patients, 145 (24.05%) tested positive by RT-PCR and RAT and 451 (74.79%) tested negative by both methods; discordant results (RT-PCR+/RAT− or RT-PCR−/RAT+) were obtained in 7 patients (1.16%). RATs’ overall specificity and sensitivity were 96.03% (95%CI: 91.55–98.53%) and 99.78% (95%CI: 98.77–99.99%), respectively, taking RT-PCR as the reference. Overall, RAT negative predictive value was 98.69% (95%CI 97.17–99.40%). The GeneFinder COVID-19 Ag Plus Rapid Test performed well as a screening test for early diagnosis of COVID-19, especially in asymptomatic subjects. The data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAT are unlikely to be infectious. GeneFinder COVID-19 Ag Plus Rapid Test also works on variants of concern (VOC) delta and omicron BA.1 and BA.2. Full article
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18 pages, 675 KiB  
Article
COVID-19 in Tunisia (North Africa): Seroprevalence of SARS-CoV-2 in the General Population of the Capital City Tunis
by Ines Cherif, Ghassen Kharroubi, Sana Chaabane, Rihab Yazidi, Mongi Dellagi, Mohamed Ali Snoussi, Sadok Salem, Soumaya Marzouki, Wafa Kammoun Rebai, Samia Rourou, Koussay Dellagi, Mohamed Ridha Barbouche, Chaouki Benabdessalem, Melika Ben Ahmed and Jihene Bettaieb
Diagnostics 2022, 12(4), 971; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12040971 - 13 Apr 2022
Cited by 6 | Viewed by 2800
Abstract
Seroprevalence studies are essential to get an accurate estimate of the actual SARS-CoV-2 diffusion within populations. We report on the findings of the first serosurvey conducted in Tunis prior to the implementation of mass vaccination and analyzed factors associated with seropositivity. A household [...] Read more.
Seroprevalence studies are essential to get an accurate estimate of the actual SARS-CoV-2 diffusion within populations. We report on the findings of the first serosurvey conducted in Tunis prior to the implementation of mass vaccination and analyzed factors associated with seropositivity. A household cross sectional survey was conducted (March–April 2021) in Tunis, spanning the end of the second wave and the beginning of the third wave of COVID-19. SARS-CoV-2 specific immunoglobulin G (IgG) antibodies to the spike (S-RBD) or the nucleocapsid (N) proteins were detected by in-house ELISA tests. The survey included 1676 individuals from 431 households. The mean age and sex ratio were 43.3 ± 20.9 years and 0.6, respectively. The weighted seroprevalence of anti-N and/or anti-S-RBD IgG antibodies was equal to 38.0% (34.6–41.5). In multivariate analysis, age under 10, no tobacco use, previous diagnosis of COVID-19, a history of COVID-19 related symptoms and contact with a COVID-19 case within the household, were independently associated with higher SARS-CoV-2 seroprevalence. More than one third of people living in Tunis obtained antibodies to SARS-CoV-2. Further studies are needed to monitor changes in these figures as Tunisian population is confronted to the subsequent epidemic waves and to guide the vaccine strategy. Full article
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14 pages, 1096 KiB  
Article
Assessment of COVID-19 Molecular Testing Capacity in Jordan: A Cross-Sectional Study at the Country Level
by Bara’a Qaqish, Malik Sallam, Maysa Al-Khateeb, Erik Reisdorf and Azmi Mahafzah
Diagnostics 2022, 12(4), 909; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12040909 - 06 Apr 2022
Cited by 5 | Viewed by 3131
Abstract
Coronavirus disease 2019 (COVID-19) pandemic control measures rely on the accurate and timely diagnosis of infected individuals. Real-time polymerase chain reaction (qPCR) remains the gold-standard method for laboratory diagnosis of the disease. Delayed diagnosis due to challenges that face laboratories performing COVID-19 testing [...] Read more.
Coronavirus disease 2019 (COVID-19) pandemic control measures rely on the accurate and timely diagnosis of infected individuals. Real-time polymerase chain reaction (qPCR) remains the gold-standard method for laboratory diagnosis of the disease. Delayed diagnosis due to challenges that face laboratories performing COVID-19 testing can hinder public health control measures. Such challenges may be related to shortages in staff, equipment or materials, improper inventory management, flawed workflow, or long turnaround time (TAT). The aim of the current study was to assess the overall COVID-19 molecular testing capacity in Jordan as of April 2021. In addition, the study’s objectives included the identification of potential defects that could comprise the utility of the COVID-19 molecular testing capacity in the country. All laboratories certified by the Ministry of Health (MoH) in Jordan to conduct molecular testing for SARS-CoV-2 were invited to participate in this study. Data were obtained from the participating laboratories (those which agreed to participate) by either telephone interviews or a self-reported written questionnaire with items assessing the key aspects of COVID-19 molecular testing. The full molecular testing capacity in each laboratory was self-reported considering 24 working hours. The total number of participating laboratories was 51 out of 77 (66.2%), with the majority being affiliated with MoH (n = 17) and private laboratories (n = 20). The total molecular COVID-19 testing capacity among the participating laboratories was estimated at 574,441 tests per week, while the actual highest number of tests performed over a single week was 310,047 (54.0%, reported in March 2021). Laboratories affiliated with the MoH were operating at a level closer to their maximum capacity (87.2% of their estimated full capacity for COVID-19 testing) compared to private hospital laboratories (41.3%, p = 0.004), private laboratories (20.8%, p < 0.001), and academic/research laboratories (14.7%, p < 0.001, ANOVA). The national average daily COVID-19 molecular testing was 349.2 tests per 100,000 people in April 2021. The average TAT over the first week of April 2021 for COVID-19 testing was 932 min among the participating laboratories, with the longest TAT among MoH laboratories (mean: 1959 min) compared to private laboratories (mean: 333 min, p < 0.001). Molecular COVID-19 testing potential in Jordan has not been fully utilized, particularly for private laboratories and those belonging to academic/research centers. Supply-chain challenges and shortages in staff were identified as potential obstacles hindering the exploitation of full molecular testing capacity for COVID-19 in the country. Full article
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11 pages, 906 KiB  
Article
Evaluation of the Diagnostic Accuracy of Nasal Cavity and Nasopharyngeal Swab Specimens for SARS-CoV-2 Detection via Rapid Antigen Test According to Specimen Collection Timing and Viral Load
by Seungjun Lee, Kristin Widyasari, Hye-Ryun Yang, Jieun Jang, Taejoon Kang and Sunjoo Kim
Diagnostics 2022, 12(3), 710; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12030710 - 14 Mar 2022
Cited by 14 | Viewed by 3186
Abstract
The rapid diagnosis of SARS-CoV-2 is an essential aspect in the detection and control of the spread of COVID-19. We evaluated the accuracy of the rapid antigen test (RAT) using samples from the nasal cavity and nasopharynx based on sample collection timing and [...] Read more.
The rapid diagnosis of SARS-CoV-2 is an essential aspect in the detection and control of the spread of COVID-19. We evaluated the accuracy of the rapid antigen test (RAT) using samples from the nasal cavity and nasopharynx based on sample collection timing and viral load. We enrolled 175 patients, of which 71 patients and 104 patients had tested positive and negative, respectively, based on real time-PCR. Nasal cavity and nasopharyngeal swab samples were tested using STANDARD Q COVID-19 Ag tests (Q Ag, SD Biosensor, Korea). The sensitivity of the Q Ag test was 77.5% (95% confidence interval [CI], 67.8–87.2%) for the nasal cavity and 81.7% (95% [CI, 72.7–90.7%) for the nasopharyngeal specimens. The RAT results showed a substantial agreement between the nasal cavity and nasopharyngeal specimens (Cohen’s kappa index = 0.78). The sensitivity of the RAT for nasal cavity specimens exceeded 89% for <5 days after symptom onset (DSO) and 86% for Ct of E and RdRp < 25. The Q Ag test performed fairly well, especially in the early DSO when a high viral load was present, and the nasal cavity swab can be considered an alternative site for the rapid diagnosis of COVID-19. Full article
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13 pages, 1412 KiB  
Article
Urinalysis, but Not Blood Biochemistry, Detects the Early Renal Impairment in Patients with COVID-19
by Haifeng Zhou, Zili Zhang, Maria Dobrinina, Yalan Dong, Zhenyu Kang, Valerii Chereshnev, Desheng Hu, Zhe Zhang, Jun Zhang and Alexey Sarapultsev
Diagnostics 2022, 12(3), 602; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12030602 - 27 Feb 2022
Cited by 29 | Viewed by 4289
Abstract
Background: Coronavirus 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has created a tremendous economic and medical burden. The prevalence and prognostic value of SARS-CoV-2-induced kidney impairment remain controversial. The current study aimed to provide additional evidence on the incidence [...] Read more.
Background: Coronavirus 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has created a tremendous economic and medical burden. The prevalence and prognostic value of SARS-CoV-2-induced kidney impairment remain controversial. The current study aimed to provide additional evidence on the incidence of acute kidney injury (AKI) in COVID-19 patients and propose the use of urinalysis as a tool for screening kidney impairment. Methods: 178 patients with confirmed COVID-19 were enrolled in this retrospective cohort study. The laboratory examinations included routine blood tests, blood biochemical analyses (liver function, renal function, lipids, and glucose), blood coagulation index, lymphocyte subset and cytokine analysis, urine routine test, C-reactive protein, erythrocyte sedimentation, and serum ferritin. Results: No patient exhibited a rise in serum creatinine or Cystatin C and occurrence of AKI, and only 2.8% of patients were recorded with an elevated level of blood urea nitrogen among all cases. On the contrary, 54.2% of patients who underwent routine urine testing presented with an abnormal urinalysis as featured by proteinuria, hematuria, and leucocyturia. Conclusions: Kidney impairment is prevalent among COVID-19 patients, with an abnormal urinalysis as a clinical manifestation, implying that a routine urine test is a stronger indication of prospective kidney complication than a blood biochemistry test. Full article
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12 pages, 1224 KiB  
Article
Comparison of Rapid Nucleic Acid Extraction Methods for SARS-CoV-2 Detection by RT-qPCR
by Lívia Mara Silva, Lorena Rodrigues Riani, Marcelo Silva Silvério, Olavo dos Santos Pereira-Júnior and Frederico Pittella
Diagnostics 2022, 12(3), 601; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12030601 - 27 Feb 2022
Cited by 5 | Viewed by 2960
Abstract
Since 2020, humanity has been facing the COVID-19 pandemic, a respiratory disease caused by the SARS-CoV-2. The world’s response to pandemic went through the development of diagnostics, vaccines and medicines. Regarding diagnostics, an enormous challenge was faced due to shortage of materials to [...] Read more.
Since 2020, humanity has been facing the COVID-19 pandemic, a respiratory disease caused by the SARS-CoV-2. The world’s response to pandemic went through the development of diagnostics, vaccines and medicines. Regarding diagnostics, an enormous challenge was faced due to shortage of materials to collect and process the samples, and to perform reliable mass diagnosis by RT-qPCR. In particular, time-consuming and high cost of nucleic acid extraction procedures have hampered the diagnosis; moreover, several steps in the routine for the preparation of the material makes the extracted sample susceptible to contamination. Here two rapid nucleic acid extraction reagents were compared as extraction procedures for SARS-CoV-2 detection in clinical samples by singleplex and multiplex RT-qPCR analysis, using different transport media, samples with high and low viral load, and different PCR machines. As observed, rapid nucleic acid extraction procedures can be applied for reliable diagnosis using a TaqMan-based assay, over multiple platforms. Ultimately, prompt RNA extraction may reduce costs with reagents and plastics, the chances of contamination, and the overall time to diagnosis by RT-qPCR. Full article
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11 pages, 2501 KiB  
Article
Preclinical Validation of a Novel Injection-Molded Swab for the Molecular Assay Detection of SARS-CoV-2
by Chiara E. Ghezzi, Devon R. Hartigan, Justin P. Hardick, Rebecca Gore, Miryam Adelfio, Anyelo R. Diaz, Pamela D. McGuinness, Matthew L. Robinson, Bryan O. Buchholz and Yukari C. Manabe
Diagnostics 2022, 12(1), 206; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010206 - 15 Jan 2022
Cited by 3 | Viewed by 2407
Abstract
During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers have timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including [...] Read more.
During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers have timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swabs, has helped to expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the initial validation of a new injection-molded anterior nasal swab, ClearTip™, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs. We have also developed an in vitro anterior nasal tissue model which offers a novel, efficient, and clinically relevant validation tool to replicate the clinical swabbing workflow with high fidelity, while being accessible, safe, reproducible, and time- and cost-effective. ClearTip™ displayed greater inactivated virus release in the benchtop model, confirmed by its greater ability to report positive samples in a small clinical study in comparison to flocked swabs. We also quantified the detection of biological materials, as a proxy for viral material, in multi-center pre-clinical and clinical studies which showed a statistically significant difference in one study and a reduction in performance in comparison to flocked swabs. Taken together, these results emphasize the compelling benefits of non-absorbent injection-molded anterior nasal swabs for COVID-19 detection, comparable to standard flocked swabs. Injection-molded swabs, as ClearTip™, could have the potential to support future swab shortages, due to its manufacturing advantages, while offering benefits in comparison to highly absorbent swabs in terms of comfort, limited volume collection, and potential multiple usage. Full article
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7 pages, 2325 KiB  
Communication
COVID-19 Pulmonary Pathology: The Experience of European Pulmonary Pathologists throughout the First Two Waves of the Pandemic
by Francesco Fortarezza, Federica Pezzuto, Paul Hofman, Izidor Kern, Angel Panizo, Jan von der Thüsen, Sergei Timofeev, Gregor Gorkiewicz, Sabina Berezowska, Laurence de Leval, Cristian Ortiz-Villalón, Francesca Lunardi and Fiorella Calabrese
Diagnostics 2022, 12(1), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12010095 - 01 Jan 2022
Cited by 6 | Viewed by 1718
Abstract
Autoptic studies of patients who died from COVID-19 constitute an important step forward in improving our knowledge in the pathophysiology of SARS-CoV-2 infection. Systematic analyses of lung tissue, the organ primarily targeted by the disease, were mostly performed during the first wave of [...] Read more.
Autoptic studies of patients who died from COVID-19 constitute an important step forward in improving our knowledge in the pathophysiology of SARS-CoV-2 infection. Systematic analyses of lung tissue, the organ primarily targeted by the disease, were mostly performed during the first wave of the pandemic. Analyses of pathological lesions at different times offer a good opportunity to better understand the disease and how its evolution has been influenced mostly by new SARS-CoV-2 variants or the different therapeutic approaches. In this short report we summarize responses collected from a questionnaire survey that investigated important pathological data during the first two pandemic waves (spring-summer 2020; autumn-winter 2020–2021). The survey was submitted to expert lung pathologists from nine European countries involved in autoptic procedures in both pandemic waves. The frequency of each lung lesion was quite heterogeneous among the participants. However, a higher frequency of pulmonary superinfections, both bacterial and especially fungal, was observed in the second wave compared to the first. Obtaining a deeper knowledge of the pathological lesions at the basis of this complex and severe disease, which change over time, is crucial for correct patient management and treatment. Autoptic examination is a useful tool to achieve this goal. Full article
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11 pages, 1751 KiB  
Article
Low Represented Mutation Clustering in SARS-CoV-2 B.1.1.7 Sublineage Group with Synonymous Mutations in the E Gene
by Paolo Giuseppe Bonacci, Dalida Angela Bivona, Dafne Bongiorno, Stefano Stracquadanio, Mariacristina Massimino, Carmelo Bonomo, Alessia Stracuzzi, Paolo Pennisi, Nicolò Musso and Stefania Stefani
Diagnostics 2021, 11(12), 2286; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11122286 - 07 Dec 2021
Cited by 1 | Viewed by 1849
Abstract
Starting in 2019, the COVID-19 pandemic is a global threat that is difficult to monitor. SARS-CoV-2 is known to undergo frequent mutations, including SNPs and deletions, which seem to be transmitted together, forming clusters that define specific lineages. Reverse-Transcription quantitative PCR (RT-qPCR) has [...] Read more.
Starting in 2019, the COVID-19 pandemic is a global threat that is difficult to monitor. SARS-CoV-2 is known to undergo frequent mutations, including SNPs and deletions, which seem to be transmitted together, forming clusters that define specific lineages. Reverse-Transcription quantitative PCR (RT-qPCR) has been used for SARS-CoV-2 diagnosis and is still considered the gold standard method. Our Eukaryotic Host Pathogens Interaction (EHPI) laboratory received six SARS-CoV-2-positive samples from a Sicilian private analysis laboratory, four of which showed a dropout of the E gene. Our sequencing data revealed the presence of a synonymous mutation (c.26415 C > T, TAC > TAT) in the E gene of all four samples showing the dropout in RT-qPCR. Interestingly, these samples also harbored three other mutations (S137L—Orf1ab; N439K—S gene; A156S—N gene), which had a very low diffusion rate worldwide. This combination suggested that these mutations may be linked to each other and more common in a specific area than in the rest of the world. Thus, we decided to analyze the 103 sequences in our internal database in order to confirm or disprove our “mutation cluster hypothesis”. Within our database, one sample showed the synonymous mutation (c.26415 C > T, TAC > TAT) in the E gene. This work underlines the importance of territorial epidemiological surveillance by means of NGS and the sequencing of samples with clinical and or technical particularities, e.g., post-vaccine infections or RT-qPCR amplification failures, to allow for the early identification of these SNPs. This approach may be an effective method to detect new mutational clusters and thus to predict new emerging SARS-CoV-2 lineages before they spread globally. Full article
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10 pages, 1091 KiB  
Article
Performance Evaluation of the BZ COVID-19 Neutralizing Antibody Test for the Culture-Free and Rapid Detection of SARS-CoV-2 Neutralizing Antibodies
by Bo Kyeung Jung, Jung Yoon, Joon-Yong Bae, Jeonghun Kim, Man-Seong Park, Suk Yong Lee and Chae Seung Lim
Diagnostics 2021, 11(12), 2193; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11122193 - 25 Nov 2021
Cited by 3 | Viewed by 1652
Abstract
Rapid and accurate measurement of SARS-CoV-2 neutralizing antibodies (nAbs) can aid in understanding the development of immunity against COVID-19. This study evaluated the diagnostic performance of a rapid SARS-CoV-2 nAb detection test called the BZ COVID-19 nAb test BZ-nAb (BZ-nAb; BioZentech). Using the [...] Read more.
Rapid and accurate measurement of SARS-CoV-2 neutralizing antibodies (nAbs) can aid in understanding the development of immunity against COVID-19. This study evaluated the diagnostic performance of a rapid SARS-CoV-2 nAb detection test called the BZ COVID-19 nAb test BZ-nAb (BZ-nAb; BioZentech). Using the 90% plaque-reduction neutralization test (PRNT-90) as a reference, 104 serum specimens collected from COVID-19-positive and -negative patients were grouped into 40 PRNT-90-positive and 64 PRNT-90-negative specimens. The performance of the BZ-nAb was compared with that of the cPass surrogate virus neutralization test (cPass sVNT; Genscript). The BZ-nAb showed a sensitivity ranging from 92.5%–95.0% and specificity ranging from 96.9%–100%, whereas cPass sVNT showed a sensitivity of 100% (95% confidence interval (CI) 90.5%–100%) and specificity of 98.4% (95% CI, 91.6%–100%). The dilution factor obtained with PRNT-90 showed a stronger correlation with the percent inhibition of cPass sVNT (r = 0.8660, p < 0.001) compared with the test and control line ratio (T/C ratio) of the BZ-nAb (r = −0.7089, p < 0.001). An almost perfect agreement was seen between the BZ-nAb and cPass sVNT results, with a strong negative correlation between the BZ-nAb T/C ratio and cPass sVNT percent inhibition (r = −0.8022, p < 0.001). In conclusion, the diagnostic performance of the BZ-nAb was comparable to that of the cPass sVNT, although the BZ-nAb had a slightly lower sensitivity. Full article
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9 pages, 1762 KiB  
Article
Diagnostic Performance of Automated SARS-CoV-2 Antigen Assay in Nasal Swab during COVID-19 Vaccination Campaign
by Haya Altawalah, Wadha Alfouzan, Talal Al-Fadalah and Sayeh Ezzikouri
Diagnostics 2021, 11(11), 2110; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112110 - 15 Nov 2021
Cited by 6 | Viewed by 2239
Abstract
Background: To control the spread of the pandemic brought about by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it is necessary to have an automated reliable diagnostic assay. To date, the RT-PCR (RT-qPCR) has been the recommended laboratory method to diagnose [...] Read more.
Background: To control the spread of the pandemic brought about by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it is necessary to have an automated reliable diagnostic assay. To date, the RT-PCR (RT-qPCR) has been the recommended laboratory method to diagnose SARS-CoV-2 infection, but there is a need for more automated and reliable tests. The aim of this real-life study was to assess the diagnostic performance of DiaSorin’s LIAISON SARS-CoV-2 antigen (Ag) chemiluminescence immunoassay in detecting SARS-CoV-2 in vaccinated and unvaccinated individuals. Methods: A prospective study was performed on 300 nasopharyngeal swabs randomly collected from 31 May to 6 July 2021. Nasopharyngeal samples were assayed with DiaSorin’s LIAISON SARS-CoV-2 Ag and TaqPath™ COVID-19 multiplex RT-qPCR. Results: Of 300 participants, 150 had a RT-qPCR confirmed SARS-CoV-2 infection of whom 113 (75.33%) were also detected by the DiaSorin LIAISON SARS-CoV-2 Ag. Taking RT-qPCR as a reference, the sensitivity and specificity of the DiaSorin LIAISON SARS-CoV-2 Ag assay were evaluated as 75.33% (95% CI = 67.64–82) and 100% (95% CI = 97.57–100), respectively. When a viral load cut-off was applied for high viral load (median cycle threshold (Ct) < 18.57), the overall sensitivity was increased to 96.55% (95% CI = 88.09–99.58). Interestingly, median RT-qPCR Ct and SARS-CoV-2 Ag values were similar between fully vaccinated and unvaccinated subjects. Conclusions: Automated, quantitative LIAISON SARS-CoV-2 Ag assay shows good performance to identify SARS-CoV-2-infected individuals with moderate to high viral loads. LIAISON SARS-CoV-2 Ag testing could be used as frontline testing for COVID-19 diagnosis and be more suitable for large utilization. Full article
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14 pages, 452 KiB  
Article
Long-Term Cardiac Sequelae in Patients Referred into a Diagnostic Post-COVID-19 Pathway: The Different Impacts on the Right and Left Ventricles
by Giovanna Pelà, Matteo Goldoni, Chiara Cavalli, Felice Perrino, Sara Tagliaferri, Annalisa Frizzelli, Pier Anselmo Mori, Maria Majori, Marina Aiello, Nicola Sverzellati, Massimo Corradi and Alfredo Chetta
Diagnostics 2021, 11(11), 2059; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112059 - 06 Nov 2021
Cited by 14 | Viewed by 2038
Abstract
Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 [...] Read more.
Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features’ data about the acute phase along with information about the follow-up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-up of 5 months, echocardiography showed morpho-functional characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and bi-ventricular systolic–diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High-Resolution computed tomography score and hemodynamic Instability (HI), and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies. Full article
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9 pages, 586 KiB  
Article
Do We Really Need Hazard Prevention at the Expense of Safeguarding Death Dignity in COVID-19?
by Cristoforo Pomara, Francesco Sessa, Domenico Galante, Lorenzo Pace, Antonio Fasanella, Nunzio Di Nunno, Massimiliano Esposito and Monica Salerno
Diagnostics 2021, 11(10), 1913; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101913 - 15 Oct 2021
Cited by 6 | Viewed by 1571
Abstract
To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long [...] Read more.
To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long SARS-CoV-2 persists with replication capacity in the tissues of individuals who died with/from COVID-19, thereby generating infectious hazards. Sixteen patients who died with/from COVID-19 who underwent autopsy between April 2020 and April 2021 were included in this study. Based on PMI, all samples were subdivided into two groups: ‘short PMI’ group (eight subjects who were autopsied between 12 to 72 h after death); ‘long PMI’ (eight subjects who were autopsied between 24 to 78 days after death). All patients tested positive for RT-PCR at nasopharyngeal swab both before death and on samples collected during post-mortem investigation. Moreover, a lung specimen was collected and frozen at −80 °C in order to perform viral culture. The result was defined based on the cytopathic effect (subjective reading) combined with the positivity of the RT-PCR test (objective reading) in the supernatant. Only in one sample (PMI 12 h), virus vitality was demonstrated. This study, supported by a literature review, suggests that the risk of cadaveric infection in cases of a person who died from/with COVID-19 is extremely low in the first hours after death, becoming null after 12 h after death, confirming the World Health Organization (WHO) assumed in March 2020 and suggesting that the corpse of a subject who died from/with COVID-19 should be generally considered not infectious. Full article
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12 pages, 2699 KiB  
Article
A Novel Rapid Test to Detect Anti-SARS-CoV-2 N Protein IgG Based on Shear Horizontal Surface Acoustic Wave (SH-SAW)
by Yu-Chi Peng, Chia-Hsuan Cheng, Hiromi Yatsuda, Szu-Heng Liu, Shih-Jen Liu, Takashi Kogai, Chen-Yen Kuo and Robert Y. L. Wang
Diagnostics 2021, 11(10), 1838; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101838 - 05 Oct 2021
Cited by 11 | Viewed by 2727
Abstract
Since the Coronavirus disease 2019 (COVID-19) pandemic outbreak, many methods have been used to detect antigens or antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including viral culture, nucleic acid test, and immunoassay. The shear-horizontal surface acoustic wave (SH-SAW) biosensor is a [...] Read more.
Since the Coronavirus disease 2019 (COVID-19) pandemic outbreak, many methods have been used to detect antigens or antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including viral culture, nucleic acid test, and immunoassay. The shear-horizontal surface acoustic wave (SH-SAW) biosensor is a novel pathogen detection platform with the advantages of high sensitivity and short detection time. The objective of this study is to develop a SH-SAW biosensor to detect the anti-SARS-CoV-2 nucleocapsid antibody. The rabbit sera collected from rabbits on different days after SARS-CoV-2 N protein injection were evaluated by SH-SAW biosensor and enzyme-linked immunosorbent assay (ELISA). The results showed that the SH-SAW biosensor achieved a high correlation coefficient (R = 0.9997) with different concentrations (34.375–1100 ng/mL) of the “spike-in” anti-N protein antibodies. Compared to ELISA, the SH-SAW biosensor has better sensitivity and can detect anti-N protein IgG signals earlier than ELISA on day 6 (p < 0.05). Overall, in this study, we demonstrated that the SH-SAW biosensor is a promising platform for rapid in vitro diagnostic (IVD) testing, especially for antigen or antibody testing. Full article
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14 pages, 19182 KiB  
Article
Recombinant Protein Expression and Purification of N, S1, and RBD of SARS-CoV-2 from Mammalian Cells and Their Potential Applications
by Julio García-Cordero, Juvenal Mendoza-Ramírez, David Fernández-Benavides, Daniela Roa-Velazquez, Jessica Filisola-Villaseñor, Sandra Paola Martínez-Frías, Erik Saul Sanchez-Salguero, Carlos E. Miguel-Rodríguez, Jose L. Maravillas Montero, Jose J. Torres-Ruiz, Diana Gómez-Martín, Leopoldo Santos Argumedo, Edgar Morales-Ríos, Juan M. Alvarado-Orozco and Leticia Cedillo-Barrón
Diagnostics 2021, 11(10), 1808; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101808 - 30 Sep 2021
Cited by 12 | Viewed by 5876
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has reached an unprecedented level. There is a strong demand for diagnostic and serological supplies worldwide, making it necessary for countries to establish their own technologies to produce high-quality biomolecules. The two main viral antigens used for [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has reached an unprecedented level. There is a strong demand for diagnostic and serological supplies worldwide, making it necessary for countries to establish their own technologies to produce high-quality biomolecules. The two main viral antigens used for the diagnostics for severe acute respiratory syndrome coronavirus (SARS-CoV-2) are the structural proteins spike (S) protein and nucleocapsid (N) protein. The spike protein of SARS-CoV-2 is cleaved into S1 and S2, in which the S1 subunit has the receptor-binding domain (RBD), which induces the production of neutralizing antibodies, whereas nucleocapsid is an ideal target for viral antigen-based detection. In this study, we designed plasmids, pcDNA3.1/S1 and pcDNA3.1/N, and optimized their expression of the recombinant S1 and N proteins from SARS-CoV-2 in a mammalian system. The RBD was used as a control. The antigens were successfully purified from Expi293 cells, with high yields of the S1, N, and RBD proteins. The immunogenic abilities of these proteins were demonstrated in a mouse model. Further, enzyme-linked immunosorbent assays with human serum samples showed that the SARS-CoV-2 antigens are a suitable alternative for serological assays to identify patients infected with COVID-19. Full article
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14 pages, 2219 KiB  
Article
CT-Based Risk Stratification for Intensive Care Need and Survival in COVID-19 Patients—A Simple Solution
by Clarissa Hosse, Laura Büttner, Florian Nima Fleckenstein, Christina Maria Hamper, Martin Jonczyk, Oriane Scholz, Annette Aigner and Georg Böning
Diagnostics 2021, 11(9), 1616; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11091616 - 04 Sep 2021
Cited by 2 | Viewed by 1578
Abstract
We evaluated a simple semi-quantitative (SSQ) method for determining pulmonary involvement in computed tomography (CT) scans of COVID-19 patients. The extent of lung involvement in the first available CT was assessed with the SSQ method and subjectively. We identified risk factors for the [...] Read more.
We evaluated a simple semi-quantitative (SSQ) method for determining pulmonary involvement in computed tomography (CT) scans of COVID-19 patients. The extent of lung involvement in the first available CT was assessed with the SSQ method and subjectively. We identified risk factors for the need of invasive ventilation, intensive care unit (ICU) admission and for time to death after infection. Additionally, the diagnostic performance of both methods was evaluated. With the SSQ method, a 10% increase in the affected lung area was found to significantly increase the risk for need of ICU treatment with an odds ratio (OR) of 1.68 and for invasive ventilation with an OR of 1.35. Male sex, age, and pre-existing chronic lung disease were also associated with higher risks. A larger affected lung area was associated with a higher instantaneous risk of dying (hazard ratio (HR) of 1.11) independently of other risk factors. SSQ measurement was slightly superior to the subjective approach with an AUC of 73.5% for need of ICU treatment and 72.7% for invasive ventilation. SSQ assessment of the affected lung in the first available CT scans of COVID-19 patients may support early identification of those with higher risks for need of ICU treatment, invasive ventilation, or death. Full article
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16 pages, 2929 KiB  
Article
Forecasting COVID-19 Severity by Intelligent Optical Fingerprinting of Blood Samples
by Simão P. Faria, Cristiana Carpinteiro, Vanessa Pinto, Sandra M. Rodrigues, José Alves, Filipe Marques, Marta Lourenço, Paulo H. Santos, Angélica Ramos, Maria J. Cardoso, João T. Guimarães, Sara Rocha, Paula Sampaio, David A. Clifton, Mehak Mumtaz and Joana S. Paiva
Diagnostics 2021, 11(8), 1309; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11081309 - 21 Jul 2021
Cited by 5 | Viewed by 3716
Abstract
Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease [...] Read more.
Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease severity immediately after diagnosis. ICU admission was the primary outcome used to define disease severity. We developed a stacking ensemble machine learning model including the backscattered signal features (optical fingerprint), patient comorbidities, and age (AUROC = 0.80), which significantly outperformed the predictive value of clinical and laboratory variables available at hospital admission (AUROC = 0.71). The information derived from patient optical fingerprints was not strongly correlated with any clinical/laboratory variable, suggesting that optical fingerprinting brings unique information for COVID-19 severity risk assessment. Optical fingerprinting is a label-free, real-time, and low-cost technology that can be easily integrated as a front-line tool to facilitate the triage and clinical management of COVID-19 patients. Full article
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10 pages, 2618 KiB  
Article
Limitation of Screening of Different Variants of SARS-CoV-2 by RT-PCR
by Agathe Boudet, Robin Stephan, Sophie Bravo, Milène Sasso and Jean-Philippe Lavigne
Diagnostics 2021, 11(7), 1241; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11071241 - 12 Jul 2021
Cited by 12 | Viewed by 3219
Abstract
Since January 2021, the diffusion of the most propagated SARS-CoV-2 variants in France (UK variant 20I/501Y.V1 (lineage B.1.1.7), 20H/H501Y.V2 (lineage B.1.351) and 20J/H501Y.V3 (lineage P.1)) were urgently screened, needing a surveillance with an RT-PCR screening assay. In this study, we evaluated one RT-PCR [...] Read more.
Since January 2021, the diffusion of the most propagated SARS-CoV-2 variants in France (UK variant 20I/501Y.V1 (lineage B.1.1.7), 20H/H501Y.V2 (lineage B.1.351) and 20J/H501Y.V3 (lineage P.1)) were urgently screened, needing a surveillance with an RT-PCR screening assay. In this study, we evaluated one RT-PCR kit for this screening (ID SARS-CoV-2/UK/SA Variant Triplex®, ID Solutions, Grabels, France) on 2207 nasopharyngeal samples that were positive for SARS-CoV-2. Using ID Solutions kit, 4.1% (92/2207) of samples were suspected to belonged to B.1.351 or P.1 variants. Next-generation sequencing that was performed on 67.4% (62/92) of these samples confirmed the presence of a B.1.351 variant in only 75.8% of the samples (47/62). Thirteen samples belonged to the UK variant (B.1.1.7), and two to A.27 with N501Y mutation. The thirteen with the UK variant presented one mutation in the S-gene, near the ΔH69/ΔV70 deletion (S71F or A67S), which impacted the detection of ΔH69/ΔV70 deletion. Using another screening kit (PKampVariantDetect SARS-CoV-2 RT-PCR combination 1 and 3® PerkinElmer, Waltham, MA, USA) on the misidentified samples, we observed that the two mutations, S71F or A67S, did not impact the detection of the UK variant. In conclusion, this study highlights the limitations of the screening strategy based on the detection of few mutations/deletions as well as it not being able to follow the virus evolution. Full article
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9 pages, 572 KiB  
Article
SARS-CoV-2 Antigen Detection to Expand Testing Capacity for COVID-19: Results from a Hospital Emergency Department Testing Site
by Giulia Menchinelli, Giulia De Angelis, Margherita Cacaci, Flora Marzia Liotti, Marcello Candelli, Ivana Palucci, Rosaria Santangelo, Maurizio Sanguinetti, Giuseppe Vetrugno, Francesco Franceschi and Brunella Posteraro
Diagnostics 2021, 11(7), 1211; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11071211 - 05 Jul 2021
Cited by 10 | Viewed by 3173
Abstract
Background: SARS-CoV-2 antigen detection has currently expanded the testing capacity for COVID-19, which yet relies on the SARS-CoV-2 RNA RT-PCR amplification. Objectives: To report on a COVID-19 testing algorithm from a tertiary care hospital emergency department (ED) that combines both antigen (performed on [...] Read more.
Background: SARS-CoV-2 antigen detection has currently expanded the testing capacity for COVID-19, which yet relies on the SARS-CoV-2 RNA RT-PCR amplification. Objectives: To report on a COVID-19 testing algorithm from a tertiary care hospital emergency department (ED) that combines both antigen (performed on the ED) and RT-PCR (performed outside the ED) testing. Methods: Between December 2020 and January 2021, in a priori designated, spatially separated COVID-19 or non-COVID-19 ED areas, respectively, symptomatic or asymptomatic patients received SARS-CoV-2 antigen testing on nasopharyngeal swab samples. Antigen results were promptly accessible to guide subsequent, outside performed confirmatory (RT-PCR) testing. Results: Overall, 1083 (100%) of 1083 samples in the COVID-19 area and 1815 (49.4%) of 3670 samples in the non-COVID-19 area had antigen results that required confirmation by RT-PCR. Antigen positivity rates were 12.4% (134/1083) and 3.7% (66/1815), respectively. Compared to RT-PCR testing results, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of antigen testing were, respectively, 68.0%, 98.3%, 88.8%, and 94.1% in the COVID-19 area, and 41.9%, 97.3%, 27.3%, and 98.6% in non-COVID-19 area. Practically, RT-PCR tests were avoided in 50.6% (1855/3670) of non-COVID-19 area samples (all antigen negative) from patients who, otherwise, would have needed antigen result confirmation. Conclusions: Our algorithm had value to preserve RT-PCR from avoidable usage and, importantly, to save time, which translated into a timely RT-PCR result availability in the COVID-19 area. Full article
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12 pages, 1459 KiB  
Article
Sample-Pooling Strategy for SARS-CoV-2 Detection among Students and Staff of the University of Sannio
by Immacolata Polvere, Elena Silvestri, Lina Sabatino, Antonia Giacco, Stefania Iervolino, Teresa Peluso, Rosa Guida, Lucrezia Zerillo, Romualdo Varricchio, Silvia D’Andrea, Serena Voccola, Jessica Raffaella Madera, Alberto Zullo, Romania Stilo, Pasquale Vito and Tiziana Zotti
Diagnostics 2021, 11(7), 1166; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11071166 - 26 Jun 2021
Cited by 4 | Viewed by 1928
Abstract
Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, it has been clear that testing large groups of the population was the key to stem infection and prevent the effects of the coronavirus disease of 2019, mostly among sensitive [...] Read more.
Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, it has been clear that testing large groups of the population was the key to stem infection and prevent the effects of the coronavirus disease of 2019, mostly among sensitive patients. On the other hand, time and cost-sustainability of virus detection by molecular analysis such as reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) may be a major issue if testing is extended to large communities, mainly asymptomatic large communities. In this context, sample-pooling and test grouping could offer an effective solution. Here we report the screening on 1195 oral-nasopharyngeal swabs collected from students and staff of the Università degli Studi del Sannio (University of Sannio, Benevento, Campania, Italy) and analyzed by an in-house developed multiplex RT-qPCR for SARS-CoV-2 detection through a simple monodimensional sample pooling strategy. Overall, 400 distinct pools were generated and, within 24 h after swab collection, five positive samples were identified. Out of them, four were confirmed by using a commercially available kit suitable for in vitro diagnostic use (IVD). High accuracy, sensitivity and specificity were also determined by comparing our results with a reference IVD assay for all deconvoluted samples. Overall, we conducted 463 analyses instead of 1195, reducing testing resources by more than 60% without lengthening diagnosis time and without significant losses in sensitivity, suggesting that our strategy was successful in recognizing positive cases in a community of asymptomatic individuals with minor requirements of reagents and time when compared to normal testing procedures. Full article
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12 pages, 1314 KiB  
Article
Post-Mortem Detection of SARS-CoV-2 RNA in Long-Buried Lung Samples
by Nicolò Musso, Luca Falzone, Stefano Stracquadanio, Dafne Bongiorno, Monica Salerno, Massimiliano Esposito, Francesco Sessa, Massimo Libra, Stefania Stefani and Cristoforo Pomara
Diagnostics 2021, 11(7), 1158; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11071158 - 24 Jun 2021
Cited by 20 | Viewed by 2853
Abstract
The Coronavirus Disease 19 (COVID-19) pandemic has caused an unexpected death toll worldwide. Even though several guidelines for the management of infectious corpses have been proposed, the limited number of post-mortem analyses during the pandemic has led to inaccuracies in the counting of [...] Read more.
The Coronavirus Disease 19 (COVID-19) pandemic has caused an unexpected death toll worldwide. Even though several guidelines for the management of infectious corpses have been proposed, the limited number of post-mortem analyses during the pandemic has led to inaccuracies in the counting of COVID-19 deaths and contributed to a lack of important information about the pathophysiology of the SARS-CoV-2 infection. Due to the impossibility of carrying out autopsies on all corpses, the scientific community has raised the question of whether confirmatory analyses could be performed on exhumed bodies after a long period of burial to assess the presence of SARS-CoV-2 RNA. Post-mortem lung samples were collected from 16 patients who died from COVID-19 infection and were buried for a long period of time. A custom RNA extraction protocol was developed to enhance extraction of viral RNA from degraded samples and highly sensitive molecular methods, including RT-qPCR and droplet digital PCR (ddPCR), were used to detect the presence of SARS-CoV-2 RNA. The custom extraction protocol developed allowed us to extract total RNA effectively from all lung samples collected. SARS-CoV-2 viral RNA was effectively detected in all samples by both RT-qPCR and ddPCR, regardless of the length of burial. ddPCR results confirmed the persistence of the virus in this anatomical niche and revealed high viral loads in some lung samples, suggesting active infection at the time of death. To the best of our knowledge, this is the first study to demonstrate the persistence of SARS-CoV-2 viral RNA in the lung even after a long post-mortem interval (up to 78 days). The extraction protocol herein described, and the highly sensitive molecular analyses performed, could represent the standard procedures for SARS-CoV-2 detection in degraded lung specimens. Finally, the innovative results obtained encourage post-mortem confirmatory analyses even after a long post-mortem interval. Full article
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11 pages, 2368 KiB  
Article
Assay System for Simultaneous Detection of SARS-CoV-2 and Other Respiratory Viruses
by Ho-Jae Lim, Jung-Eun Park, Min-Young Park, Joo-Hwan Baek, Sunkyung Jung, Nackmoon Sung, Jae-Hyun Yang, Min-Woo Lee, Sun-Hwa Lee and Yong-Jin Yang
Diagnostics 2021, 11(6), 1084; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11061084 - 13 Jun 2021
Cited by 10 | Viewed by 5212
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers disease with nonspecific symptoms that overlap those of infections caused by other seasonal respiratory viruses (RVs), such as the influenza virus (Flu) or respiratory syncytial virus (RSV). A molecular assay for accurate and rapid detection [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers disease with nonspecific symptoms that overlap those of infections caused by other seasonal respiratory viruses (RVs), such as the influenza virus (Flu) or respiratory syncytial virus (RSV). A molecular assay for accurate and rapid detection of RV and SARS-CoV-2 is crucial to manage these infections. Here, we compared the analytical performance and clinical reliability of Allplex™ SARS-CoV-2/FluA/FluB/RSV (SC2FabR; Seegene Inc., Seoul, South Korea) kit with those of four commercially available RV detection kits. Upon testing five target viral strains (SARS-CoV-2, FluA, FluB, RSV A, and RSV B), the analytical performance of SC2FabR was similar to that of the other kits, with no significant difference (p ≥ 0.78) in z-scores. The efficiency of SC2FabR (E-value, 81–104%) enabled reliable SARS-CoV-2 and seasonal RV detection in 888 nasopharyngeal swab specimens processed using a fully automated nucleic acid extraction platform. Bland–Altman analyses revealed an agreement value of 95.4% (SD ± 1.96) for the kits, indicating statistically similar results for all five. In conclusion, SC2FabR is a rapid and accurate diagnostic tool for both SARS-CoV-2 and seasonal RV detection, allowing for high-throughput RV analysis with efficiency comparable to that of commercially available kits. This can be used to help manage respiratory infections in patients during and after the coronavirus disease 2019 pandemic. Full article
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13 pages, 8670 KiB  
Article
Risk Stratification for ECMO Requirement in COVID-19 ICU Patients Using Quantitative Imaging Features in CT Scans on Admission
by Eva Gresser, Jakob Reich, Bastian O. Sabel, Wolfgang G. Kunz, Matthias P. Fabritius, Johannes Rübenthaler, Michael Ingrisch, Dietmar Wassilowsky, Michael Irlbeck, Jens Ricke and Daniel Puhr-Westerheide
Diagnostics 2021, 11(6), 1029; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11061029 - 03 Jun 2021
Cited by 8 | Viewed by 2239
Abstract
(1) Background: Extracorporeal membrane oxygenation (ECMO) therapy in intensive care units (ICUs) remains the last treatment option for Coronavirus disease 2019 (COVID-19) patients with severely affected lungs but is highly resource demanding. Early risk stratification for the need of ECMO therapy upon admission [...] Read more.
(1) Background: Extracorporeal membrane oxygenation (ECMO) therapy in intensive care units (ICUs) remains the last treatment option for Coronavirus disease 2019 (COVID-19) patients with severely affected lungs but is highly resource demanding. Early risk stratification for the need of ECMO therapy upon admission to the hospital using artificial intelligence (AI)-based computed tomography (CT) assessment and clinical scores is beneficial for patient assessment and resource management; (2) Methods: Retrospective single-center study with 95 confirmed COVID-19 patients admitted to the participating ICUs. Patients requiring ECMO therapy (n = 14) during ICU stay versus patients without ECMO treatment (n = 81) were evaluated for discriminative clinical prediction parameters and AI-based CT imaging features and their diagnostic potential to predict ECMO therapy. Reported patient data include clinical scores, AI-based CT findings and patient outcomes; (3) Results: Patients subsequently allocated to ECMO therapy had significantly higher sequential organ failure (SOFA) scores (p < 0.001) and significantly lower oxygenation indices on admission (p = 0.009) than patients with standard ICU therapy. The median time from hospital admission to ECMO placement was 1.4 days (IQR 0.2–4.0). The percentage of lung involvement on AI-based CT assessment on admission to the hospital was significantly higher in ECMO patients (p < 0.001). In binary logistic regression analyses for ECMO prediction including age, sex, body mass index (BMI), SOFA score on admission, lactate on admission and percentage of lung involvement on admission CTs, only SOFA score (OR 1.32, 95% CI 1.08–1.62) and lung involvement (OR 1.06, 95% CI 1.01–1.11) were significantly associated with subsequent ECMO allocation. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.83 (95% CI 0.73–0.94) for lung involvement on admission CT and 0.82 (95% CI 0.72–0.91) for SOFA scores on ICU admission. A combined parameter of SOFA on ICU admission and lung involvement on admission CT yielded an AUC of 0.91 (0.84–0.97) with a sensitivity of 0.93 and a specificity of 0.84 for ECMO prediction; (4) Conclusions: AI-based assessment of lung involvement on CT scans on admission to the hospital and SOFA scoring, especially if combined, can be used as risk stratification tools for subsequent requirement for ECMO therapy in patients with severe COVID-19 disease to improve resource management in ICU settings. Full article
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9 pages, 222 KiB  
Article
Clinical Application of a New SARS-CoV-2 Antigen Detection Kit (Colloidal Gold) in the Detection of COVID-19
by Evangelos Terpos, Ioannis Ntanasis-Stathopoulos and Miha Skvarč
Diagnostics 2021, 11(6), 995; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11060995 - 30 May 2021
Cited by 17 | Viewed by 4033
Abstract
The precise diagnosis of COVID-19 is of outmost importance in order to effectively treat patients and prevent SARS-CoV-2 transmission. Herein, we evaluated the sensitivity and specificity of the COVID-19 Antigen Detection Kit (Colloidal Gold—CG) compared with PCR in nasopharyngeal and nasal samples. A [...] Read more.
The precise diagnosis of COVID-19 is of outmost importance in order to effectively treat patients and prevent SARS-CoV-2 transmission. Herein, we evaluated the sensitivity and specificity of the COVID-19 Antigen Detection Kit (Colloidal Gold—CG) compared with PCR in nasopharyngeal and nasal samples. A total of 114 positive and 244 negative nasopharyngeal specimens confirmed by PCR were used in this comparative study. When the PCR positive Cycle Threshold (Ct) value was ≤25, CG sensitivity was 100%. When the PCR positive Ct value was ≤33, CG sensitivity was 99%. When the PCR positive Ct value was ≤40, CG sensitivity was 89.47%. Regarding nasal swabs, a total of 109 positive and 250 negative specimens confirmed by PCR were used. When the PCR positive Ct value was ≤25, CG sensitivity was 100%. When the PCR positive Ct value was ≤33, CG sensitivity was 96.12%. When the PCR positive Ct value was ≤37, CG sensitivity was 91.74%. Specificity was above 99% regardless of the Ct value of PCR positivity for both nasopharyngeal and nasal specimens. Overall, the CG showed high sensitivity and specificity when the PCR Ct value was less than 33. Therefore, CG can be used for screening early in the disease course. Confirmatory PCR is essential when a false negative result is suspected. Full article
8 pages, 688 KiB  
Communication
Presence of SARS-CoV-2 Nucleoprotein in Cardiac Tissues of Donors with Negative COVID-19 Molecular Tests
by Gianluca Lorenzo Perrucci, Elena Sommariva, Veronica Ricci, Paola Songia, Yuri D’Alessandra, Paolo Poggio, Giulio Pompilio, Gianluca Polvani and Anna Guarino
Diagnostics 2021, 11(4), 731; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11040731 - 20 Apr 2021
Cited by 5 | Viewed by 2058
Abstract
The 2019 Coronavirus disease (COVID-19) outbreak had detrimental effects on essential medical services such as organ and tissue donation. Lombardy, one of the most active Italian regions in organ/tissue procurement, has been strongly affected by the COVID-19 pandemic. To date, data concerning the [...] Read more.
The 2019 Coronavirus disease (COVID-19) outbreak had detrimental effects on essential medical services such as organ and tissue donation. Lombardy, one of the most active Italian regions in organ/tissue procurement, has been strongly affected by the COVID-19 pandemic. To date, data concerning the risk of SARS-CoV-2 transmission after tissue transplantation are controversial. Here, we aimed to evaluate the presence/absence of SARS-CoV-2 in different cardiac tissues eligible for transplantation obtained from Lombard donors. We used cardiovascular tissues from eight donors potentially suitable for pulmonary valve transplantation. All donor subjects involved in the study returned negative results for the SARS-CoV-2 RNA molecular tests (quantitative real-time reverse-transcription PCR, qRT-PCR, and chip-based digital PCR) in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL). None of the eight donors included in this study revealed the presence of the SARS-CoV-2 viral genome. However, evaluation of the protein content of pulmonary vein wall (PVW) tissue revealed variable levels of SARS-CoV-2 nucleoprotein signal in all donors. Our study demonstrated for the first time, to the best of our knowledge, that viral nucleoprotein but not viral RNA was present in the examined tissue bank specimens, suggesting the need for caution and in-depth investigations on implantable tissue specimens collected during the COVID-19 pandemic period. Full article
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14 pages, 2097 KiB  
Article
Safe Management Strategies in Clinical Forensic Autopsies of Confirmed COVID-19 Cases
by Cristoforo Pomara, Monica Salerno, Francesco Sessa, Massimiliano Esposito, Martina Barchitta, Caterina Ledda, Patrizia Grassi, Aldo Liberto, Anna Rita Mattaliano, Venerando Rapisarda, Margherita Ferrante and Antonella Agodi
Diagnostics 2021, 11(3), 457; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11030457 - 06 Mar 2021
Cited by 20 | Viewed by 3066
Abstract
To date, there is poor evidence on the transmission of infection in individuals handling the bodies of deceased persons infected with SARS-CoV-2 and in particular, during autopsies. The aim of this study was to demonstrate that when appropriate strategies are adopted autopsy is [...] Read more.
To date, there is poor evidence on the transmission of infection in individuals handling the bodies of deceased persons infected with SARS-CoV-2 and in particular, during autopsies. The aim of this study was to demonstrate that when appropriate strategies are adopted autopsy is a safe procedure with a minimal infection risk for all subjects involved (pathologists, technical personnel, and others) when proper strategies are adopted. We performed 16 autopsies on cadavers of persons who had died with confirmed COVID-19 with different post-mortem intervals (PMI). To confirm the presence of SARS-CoV-2 RNA, for each autopsy, 2 swabs were sampled from lungs, while to evaluate environmental contamination, 11 swabs were taken at three different times: T0 (before autopsy), T1 (at the end of the autopsy, without removing the corpse), and T2 (after cleaning and disinfecting the autopsy room). Specifically, 2 swabs were sampled on face shields used by each pathologist, and 4 swabs were collected on the autopsy table; 4 swabs were also collected from walls and 1 from floor. Lung swabs confirmed the presence of SARS-CoV-2 RNA in all cases. Environmental swabs, collected at T0 and T2 were all negative, while swabs sampled at T1 were shown to be positive. Interestingly, no association was shown between PMI length and environmental contamination. Infection control strategies for safe management of clinical forensic autopsies of bodies with suspected or confirmed COVID-19 are also described. Full article
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Review

Jump to: Research, Other

14 pages, 944 KiB  
Review
Microbiological and Clinical Findings of SARS-CoV-2 Infection after 2 Years of Pandemic: From Lung to Gut Microbiota
by Alessandro Russo, Francesca Serapide, Angela Quirino, Maria Grazia Tarsitano, Nadia Marascio, Riccardo Serraino, Salvatore Rotundo, Giovanni Matera, Enrico Maria Trecarichi and Carlo Torti
Diagnostics 2022, 12(9), 2143; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12092143 - 02 Sep 2022
Cited by 4 | Viewed by 1519
Abstract
Early recognition and prompt management are crucial for improving survival in COVID-19 patients, and after 2 years of the pandemic, many efforts have been made to obtain an early diagnosis. A key factor is the use of fast microbiological techniques, considering also that [...] Read more.
Early recognition and prompt management are crucial for improving survival in COVID-19 patients, and after 2 years of the pandemic, many efforts have been made to obtain an early diagnosis. A key factor is the use of fast microbiological techniques, considering also that COVID-19 patients may show no peculiar signs and symptoms that may differentiate COVID-19 from other infective or non-infective diseases. These techniques were developed to promptly identify SARS-CoV-2 infection and to prevent viral spread and transmission. However, recent data about clinical, radiological and laboratory features of COVID-19 at time of hospitalization could help physicians in early suspicion of SARS-CoV-2 infection and distinguishing it from other etiologies. The knowledge of clinical features and microbiological techniques will be crucial in the next years when the endemic circulation of SARS-CoV-2 will be probably associated with clusters of infection. In this review we provide a state of the art about new advances in microbiological and clinical findings of SARS-CoV-2 infection in hospitalized patients with a focus on pulmonary and extrapulmonary characteristics, including the role of gut microbiota. Full article
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10 pages, 2252 KiB  
Review
The Composition and Physical Properties of Clots in COVID-19 Pathology
by Sierk Dauwerse, Hugo ten Cate, Henri M. H. Spronk and Magdolna Nagy
Diagnostics 2022, 12(3), 580; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12030580 - 24 Feb 2022
Cited by 2 | Viewed by 2786
Abstract
Hemostasis is a finely tuned process of which dysregulation can lead either to bleeding or thrombotic complications. The latter is often caused by the hypercoagulable state as it is also seen in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, i.e., [...] Read more.
Hemostasis is a finely tuned process of which dysregulation can lead either to bleeding or thrombotic complications. The latter is often caused by the hypercoagulable state as it is also seen in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, i.e., in COVID-19 patients. COVID-19 patients requiring hospitalization often suffer from thrombotic events that could not be predicted using routine coagulation assays. Recently, several studies have reported ROtational ThromboElastoMetry (ROTEM) as a promising tool to predict outcomes in COVID-19 patients. In this review we give an overview of ROTEM with a particular focus on the interpretation of the symmetrical clot formation curve in relation to coagulopathy in COVID-19 patients. Furthermore, we have introduced new parameters that might help to better distinguish between COVID-19 patients and outcomes. Full article
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20 pages, 346 KiB  
Review
Diagnostic Approaches for COVID-19 and Its Associated Complications
by Ivan E. Wang, Grant Cooper and Shaker A. Mousa
Diagnostics 2021, 11(11), 2071; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112071 - 09 Nov 2021
Cited by 6 | Viewed by 2414
Abstract
With almost 4 million deaths worldwide from the COVID-19 pandemic, the efficient and accurate diagnosis and identification of COVID-19-related complications are more important than ever. Scales such as the pneumonia severity index, or CURB-65, help doctors determine who should be admitted to the [...] Read more.
With almost 4 million deaths worldwide from the COVID-19 pandemic, the efficient and accurate diagnosis and identification of COVID-19-related complications are more important than ever. Scales such as the pneumonia severity index, or CURB-65, help doctors determine who should be admitted to the hospital or the intensive care unit. To properly treat and manage admitted patients, standardized sampling protocols and methods are required for COVID-19 patients. Using PubMed, relevant articles since March 2020 on COVID-19 diagnosis and its complications were analyzed. Patients with COVID-19 had elevated D-dimer, thrombomodulin, and initial factor V elevation followed by decreased factor V and factor VII and elevated IL-6, lactate dehydrogenase, and c-reactive protein, which indicated coagulopathy and possible cytokine storm. Patients with hypertension, newly diagnosed diabetes, obesity, or advanced age were at increased risk for mortality. Elevated BUN, AST, and ALT in severe COVID-19 patients was associated with acute kidney injury or other organ damage. The gold standard for screening COVID-19 is reverse transcriptase polymerase chain reaction (RT-PCR) using sputum, oropharyngeal, or nasopharyngeal routes. However, due to the low turnover rate and limited testing capacity of RT-PCR, alternative diagnostic tools such as CT-scan and serological testing (IgM and IgG) can be considered in conjunction with symptom monitoring. Advancements in CRISPR technology have also allowed the use of alternative COVID-19 testing, but unfortunately, these technologies are still under FDA review and cannot be used in patients. Nonetheless, increased turnover rates and testing capacity allow for a bright future in COVID-19 diagnosis. Full article
12 pages, 1473 KiB  
Review
The Role of Bronchoscopy in the Diagnosis and Management of Patients with SARS-Cov-2 Infection
by Davide Biondini, Marco Damin, Martina Bonifazi, Elisabetta Cocconcelli, Umberto Semenzato, Paolo Spagnolo, Stefano Gasparini, Marina Saetta and Elisabetta Balestro
Diagnostics 2021, 11(10), 1938; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101938 - 19 Oct 2021
Cited by 3 | Viewed by 4301
Abstract
Bronchoscopy has several major diagnostic and therapeutic indications in pulmonology. However, it is an aerosol-generating procedure that places healthcare providers at an increased risk of infection. Now more than ever, during the spread of the coronavirus disease 2019 (COVID-19) pandemic, the infectious risk [...] Read more.
Bronchoscopy has several major diagnostic and therapeutic indications in pulmonology. However, it is an aerosol-generating procedure that places healthcare providers at an increased risk of infection. Now more than ever, during the spread of the coronavirus disease 2019 (COVID-19) pandemic, the infectious risk during bronchoscopy is significantly raised, and for this reason its role in diagnostic management is debated. In this review, we summarized current evidence regarding the indications for bronchoscopy and the measures that should be applied to decrease risk exposure. Indeed, seeing the long-lasting period of the pandemic, resuming standard of care for all patients is required. Full article
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17 pages, 1591 KiB  
Review
Detection of COVID-19 Virus on Surfaces Using Photonics: Challenges and Perspectives
by Bakr Ahmed Taha, Yousif Al Mashhadany, Nur Nadia Bachok, Ahmad Ashrif A Bakar, Mohd Hadri Hafiz Mokhtar, Mohd Saiful Dzulkefly Bin Zan and Norhana Arsad
Diagnostics 2021, 11(6), 1119; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11061119 - 19 Jun 2021
Cited by 33 | Viewed by 5653
Abstract
The propagation of viruses has become a global threat as proven through the coronavirus disease (COVID-19) pandemic. Therefore, the quick detection of viral diseases and infections could be necessary. This study aims to develop a framework for virus diagnoses based on integrating photonics [...] Read more.
The propagation of viruses has become a global threat as proven through the coronavirus disease (COVID-19) pandemic. Therefore, the quick detection of viral diseases and infections could be necessary. This study aims to develop a framework for virus diagnoses based on integrating photonics technology with artificial intelligence to enhance healthcare in public areas, marketplaces, hospitals, and airfields due to the distinct spectral signatures from lasers’ effectiveness in the classification and monitoring of viruses. However, providing insights into the technical aspect also helps researchers identify the possibilities and difficulties in this field. The contents of this study were collected from six authoritative databases: Web of Science, IEEE Xplore, Science Direct, Scopus, PubMed Central, and Google Scholar. This review includes an analysis and summary of laser techniques to diagnose COVID-19 such as fluorescence methods, surface-enhanced Raman scattering, surface plasmon resonance, and integration of Raman scattering with SPR techniques. Finally, we select the best strategies that could potentially be the most effective methods of reducing epidemic spreading and improving healthcare in the environment. Full article
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13 pages, 1313 KiB  
Review
Test Groups, Not Individuals: A Review of the Pooling Approaches for SARS-CoV-2 Diagnosis
by Renato Millioni and Cinzia Mortarino
Diagnostics 2021, 11(1), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11010068 - 04 Jan 2021
Cited by 8 | Viewed by 2721
Abstract
Massive molecular testing for SARS-CoV-2 diagnosis is mandatory to manage the spread of COVID-19. Diagnostic screening should be performed at a mass scale, extended to the asymptomatic population, and repeated over time. An accurate diagnostic pipeline for SARS-CoV-2 that could massively increase the [...] Read more.
Massive molecular testing for SARS-CoV-2 diagnosis is mandatory to manage the spread of COVID-19. Diagnostic screening should be performed at a mass scale, extended to the asymptomatic population, and repeated over time. An accurate diagnostic pipeline for SARS-CoV-2 that could massively increase the laboratory efficiency, while being sustainable in terms of time and costs, should be based on a pooling strategy. In the past few months, researchers from different disciplines had this same idea: test groups, not individuals. This critical review intends to highlight both the general consents—even if the results from different publications have been obtained with different protocols—and the points of disagreement that are creating some interpretative/comprehension difficulties. Different pooling schemes and technical aspects associated to the type of pooling adopted are described and discussed. We hope that this review can consolidate information to support researchers in designing optimized COVID-19 testing protocols based on pooling. Full article
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9 pages, 863 KiB  
Interesting Images
The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review
by Irene Fatuzzo, Andrea Colizza, Piero Giuseppe Meliante, Haitham Elfarargy, Roger Altomari, Marco Fiore, Massimo Ralli, Daniela Messineo, Antonio Greco, Marco de Vincentiis, Christian Barbato and Antonio Minni
Diagnostics 2023, 13(5), 905; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13050905 - 27 Feb 2023
Cited by 1 | Viewed by 1352
Abstract
Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a [...] Read more.
Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures. Full article
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10 pages, 627 KiB  
Systematic Review
Wearable Technology for Monitoring Respiratory Rate and SpO2 of COVID-19 Patients: A Systematic Review
by Shizuko Takahashi, Eisuke Nakazawa, Sakurako Ichinohe, Aru Akabayashi and Akira Akabayashi
Diagnostics 2022, 12(10), 2563; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12102563 - 21 Oct 2022
Cited by 5 | Viewed by 2381
Abstract
With the significant numbers of sudden home deaths reported worldwide due to coronavirus disease 2019 (COVID-19), wearable technology has emerged as a method for surveilling this infection. This review explored the indicators of COVID-19 surveillance, such as vitals, respiratory condition, temperature, oxygen saturation [...] Read more.
With the significant numbers of sudden home deaths reported worldwide due to coronavirus disease 2019 (COVID-19), wearable technology has emerged as a method for surveilling this infection. This review explored the indicators of COVID-19 surveillance, such as vitals, respiratory condition, temperature, oxygen saturation (SpO2), and activity levels using wearable devices. Studies published between 31 December 2019, and 8 July 2022, were obtained from PubMed, and grey literature, reference lists, and key journals were also searched. All types of articles with the keywords “COVID-19”, “Diagnosis”, and “Wearable Devices” were screened. Four reviewers independently screened the articles against the eligibility criteria and extracted the data using a data charting form. A total of 56 articles were on monitoring, of which 28 included SpO2 as a parameter. Although wearable devices are effective in the continuous monitoring of COVID-19 patients, further research on actual patients is necessary to determine the efficiency and effectiveness of wearable technology before policymakers can mandate its use. Full article
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14 pages, 2316 KiB  
Case Report
COVID-19 Syndemic: Convergence of COVID-19, Pulmonary Aspergillosis (CAPA), Pulmonary Tuberculosis, Type 2 Diabetes Mellitus, and Arterial Hypertension
by Jose Isaias Badillo-Almaraz, Sergio Andres Cardenas-Cadena, Fausto Daniel Gutierrez-Avella, Pedro Javier Villegas-Medina, Idalia Garza-Veloz, Valentin Badillo Almaraz and Margarita L Martinez-Fierro
Diagnostics 2022, 12(9), 2058; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12092058 - 25 Aug 2022
Viewed by 2012
Abstract
Bacterial coinfections, which increase the severity of respiratory viral infections, are frequent causes of mortality in influenza pandemics but have not been well characterized in patients with Coronavirus disease 2019 (COVID-19). Moreover, the association of COVID-19 infection with pulmonary Mycobacterium tuberculosis disease (TB) [...] Read more.
Bacterial coinfections, which increase the severity of respiratory viral infections, are frequent causes of mortality in influenza pandemics but have not been well characterized in patients with Coronavirus disease 2019 (COVID-19). Moreover, the association of COVID-19 infection with pulmonary Mycobacterium tuberculosis disease (TB) and concurrent pulmonary fungal infection is not well known. The classification of patients with COVID-19-associated pulmonary aspergillosis (CAPA) using the current definitions for invasive fungal diseases has proven difficult. In this study, we aimed to provide information about three patients with underlying diseases ongoing with COVID-19 and co-infection with pulmonary TB, and with COVID-19-associated pulmonary aspergillosis (CAPA). At the time of hospital admission, each patient presented complications such as decompensated T2DM with diabetic ketoacidosis and/or hypertension. Findings of chest computed tomography and serum galactomannan by radioimmunoassay were useful for classifying them as possible CAPA. One of the three possible CAPA cases was fatal. These three cases are rare and are the first of their kind reported worldwide. The generation of reliable algorithms, early diagnosis, standardization of classification criteria, and the selection of specific and personalized treatments for COVID-19-associated opportunistic infections, including CAPA, are necessary to improve outcomes in these kinds of patients. Full article
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13 pages, 2525 KiB  
Systematic Review
Association between Fibrinogen-to-Albumin Ratio and Prognosis of Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis
by Kuo-Chuan Hung, Yen-Ta Huang, Ying-Jen Chang, Chia-Hung Yu, Li-Kai Wang, Chung-Yi Wu, Ping-Hsin Liu, Sheng-Fu Chiu and Cheuk-Kwan Sun
Diagnostics 2022, 12(7), 1678; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12071678 - 10 Jul 2022
Cited by 3 | Viewed by 1950
Abstract
Although the fibrinogen-to-albumin ratio (F/R ratio) has been used as an inflammation marker to predict clinical outcomes in patients with cardiovascular diseases, its association with the prognosis of patients with coronavirus disease 2019 (COVID-19) remains unclear. Electronic databases including EMBASE, MEDLINE, Google Scholar, [...] Read more.
Although the fibrinogen-to-albumin ratio (F/R ratio) has been used as an inflammation marker to predict clinical outcomes in patients with cardiovascular diseases, its association with the prognosis of patients with coronavirus disease 2019 (COVID-19) remains unclear. Electronic databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to 20 June 2022. The associations of F/R ratio with poor prognosis (defined as the occurrence of mortality or severe disease) were investigated in patients with COVID-19. A total of 10 studies (seven from Turkey, two from China, one from Croatia) involving 3675 patients published between 2020 and 2022 were eligible for quantitative syntheses. Merged results revealed a higher F/R ratio in the poor prognosis group (standardized mean difference: 0.529, p < 0.001, I2 = 84.8%, eight studies) than that in the good prognosis group. In addition, a high F/R ratio was associated with an increased risk of poor prognosis (odds ratio: 2.684, I2 = 59.5%, five studies). Pooled analysis showed a sensitivity of 0.75, specificity of 0.66, and area under curve of 0.77 for poor prognosis prediction. In conclusion, this meta-analysis revealed a positive correlation between F/A ratio and poor prognostic outcomes of COVID-19. Because of the limited number of studies included, further investigations are warranted to support our findings. Full article
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15 pages, 2224 KiB  
Systematic Review
Association of Prognostic Nutritional Index with Severity and Mortality of Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis
by Kuo-Chuan Hung, Ching-Chung Ko, Li-Kai Wang, Ping-Hsin Liu, I-Wen Chen, Yen-Ta Huang and Cheuk-Kwan Sun
Diagnostics 2022, 12(7), 1515; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12071515 - 21 Jun 2022
Cited by 9 | Viewed by 2170
Abstract
The associations of prognostic nutritional index (PNI) with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19) remain unclear. Electronic databases, including MEDLINE, EMBASE, Google scholar, and Cochrane Library, were searched from inception to 10 May 2022. The associations of PNI [...] Read more.
The associations of prognostic nutritional index (PNI) with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19) remain unclear. Electronic databases, including MEDLINE, EMBASE, Google scholar, and Cochrane Library, were searched from inception to 10 May 2022. The associations of PNI with risk of mortality (primary outcome) and disease severity (secondary outcome) were investigated. Merged results from meta-analysis of 13 retrospective studies (4204 patients) published between 2020 and 2022 revealed a lower PNI among patients in the mortality group [mean difference (MD): −8.65, p < 0.001] or severity group (MD: −5.19, p < 0.001) compared to those in the non-mortality or non-severity groups. A per-point increase in PNI was associated with a reduced risk of mortality [odds ratio (OR) = 0.84, 95% CI: 0.79 to 0.9, p < 0.001, I2 = 67.3%, seven studies] and disease severity (OR = 0.84, 95% CI: 0.77 to 0.92, p < 0.001, I2 = 83%, five studies). The pooled diagnostic analysis of mortality yielded a sensitivity of 0.76, specificity of 0.71, and area under curve (AUC) of 0.79. Regarding the prediction of disease severity, the sensitivity, specificity, and AUC were 0.8, 0.61, and 0.65, respectively. In conclusion, this study demonstrated a negative association between PNI and prognosis of COVID-19. Further large-scale trials are warranted to support our findings. Full article
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17 pages, 1588 KiB  
Systematic Review
Diagnostic Performance of Antigen Rapid Diagnostic Tests, Chest Computed Tomography, and Lung Point-of-Care-Ultrasonography for SARS-CoV-2 Compared with RT-PCR Testing: A Systematic Review and Network Meta-Analysis
by Sung Ryul Shim, Seong-Jang Kim, Myunghee Hong, Jonghoo Lee, Min-Gyu Kang and Hyun Wook Han
Diagnostics 2022, 12(6), 1302; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12061302 - 24 May 2022
Cited by 2 | Viewed by 2795
Abstract
(1) Background: The comparative performance of various diagnostic methods for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remains unclear. This study aimed to investigate the comparison of the 3 index test performances of rapid antigen diagnostic tests (RDTs), chest computed tomography (CT), and [...] Read more.
(1) Background: The comparative performance of various diagnostic methods for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remains unclear. This study aimed to investigate the comparison of the 3 index test performances of rapid antigen diagnostic tests (RDTs), chest computed tomography (CT), and lung point-of-care-ultrasonography (US) with reverse transcription-polymerase chain reaction (RT-PCR), the reference standard, to provide more evidence-based data on the appropriate use of these index tests. (2) Methods: We retrieved data from electronic literature searches of PubMed, Cochrane Library, and EMBASE from 1 January 2020, to 1 April 2021. Diagnostic performance was examined using bivariate random-effects diagnostic test accuracy (DTA) and Bayesian network meta-analysis (NMA) models. (3) Results: Of the 3992 studies identified in our search, 118 including 69,445 participants met our selection criteria. Among these, 69 RDT, 38 CT, and 15 US studies in the pairwise meta-analysis were included for DTA with NMA. CT and US had high sensitivity of 0.852 (95% credible interval (CrI), 0.791–0.914) and 0.879 (95% CrI, 0.784–0.973), respectively. RDT had high specificity, 0.978 (95% CrI, 0.960–0.996). In accuracy assessment, RDT and CT had a relatively higher than US. However, there was no significant difference in accuracy between the 3 index tests. (4) Conclusions: This meta-analysis suggests that, compared with the reference standard RT-PCR, the 3 index tests (RDTs, chest CT, and lung US) had similar and complementary performances for diagnosis of SARS-CoV-2 infection. To manage and control COVID-19 effectively, future large-scale prospective studies could be used to obtain an optimal timely diagnostic process that identifies the condition of the patient accurately. Full article
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9 pages, 2639 KiB  
Case Report
Implementation of a Rapid RT-LAMP Saliva-Based SARS-CoV-2 Testing Program in the Workplace
by Bradley W. M. Cook, Kaitlyn Kobasa, Marielou Tamayo, Natasha Theriault, Diane Gordon Pappas and Steven S. Theriault
Diagnostics 2022, 12(2), 474; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12020474 - 12 Feb 2022
Cited by 3 | Viewed by 1699
Abstract
Rising SARS-CoV-2 cases, testing delays, and the risk of pre-symptomatic and asymptomatic transmission provided the impetus for an in-house rapid testing program. Employees and their household contacts were encouraged to self-collect saliva samples that were pooled for routine testing using an established colorimetric [...] Read more.
Rising SARS-CoV-2 cases, testing delays, and the risk of pre-symptomatic and asymptomatic transmission provided the impetus for an in-house rapid testing program. Employees and their household contacts were encouraged to self-collect saliva samples that were pooled for routine testing using an established colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. In brief, individual or a maximum of four saliva samples were pooled and heat-inactivated to render microorganisms, especially SARS-CoV-2, non-infectious prior to being added to RT-LAMP assay tubes containing either the human sample control gene, RNase P, or a region of the SARS-CoV-2 gene, ORF1ab. During the second wave of SARS-CoV-2 infections in November 2020, two samples from an employee and a member of their household tested positive via RT-LAMP within two days of each other. A delayed clinical qRT-PCR test confirmation of both individuals 5 days later underscored the power of routine rapid testing with within-the-hour turnaround times. Workplace rapid testing programs using RT-LAMP are flexible in their design, have a reduced cost compared to qRT-PCR, may involve non-invasive self-saliva collection for increased safety for the testing personnel, and can be performed with minimal training. Full article
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8 pages, 206 KiB  
Brief Report
Prospective Observational COVID-19 Screening and Monitoring of Asymptomatic Cancer Center Health-Care Workers with a Rapid Serological Test
by Angelo Virgilio Paradiso, Simona De Summa, Nicola Silvestris, Stefania Tommasi, Antonio Tufaro, Angela Maria Vittoria Larocca, Vincenzo D’Addabbo, Donata Raffaele, Vito Cafagna, Vito Michele Garrisi and Giuseppe De Palma
Diagnostics 2021, 11(6), 975; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11060975 - 28 May 2021
Cited by 4 | Viewed by 2116
Abstract
Health-care workers (HCW) are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus to fragile cancer patients. We monitored all asymptomatic HCWs of a cancer institute (94% of all employees agreed to enter the study) with the rapid serological [...] Read more.
Health-care workers (HCW) are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus to fragile cancer patients. We monitored all asymptomatic HCWs of a cancer institute (94% of all employees agreed to enter the study) with the rapid serological test, VivaDiagTM, identifying SARS-CoV-2 associated-IgM/IgG. The tests were performed at time 0 (n = 606) and after 14 days (n = 393). Overall, the VivaDiagTM results of nine HCWs (1.5%) were positive, with one confirmed to be SARS-CoV-2-positive after oropharyngeal swab testing by RT-PCR. At time 0, all nine cases showed IgM expression while IgG was detected in only one. After 14 days, IgM persisted in all the cases, while IgG became evident in four. A chemiluminescence immunoassay (CLIA) confirmed IgM positivity in 5/13 VivaDiagTM positive cases and IgG positivity in 4/5 VivaDiagTM positive cases. Our study suggests that the VivaDiagTM test can be of help in identifying SARS-CoV-2 infected people in cohorts of subjects with a high prevalence. Full article
7 pages, 784 KiB  
Brief Report
Seroprevalence of Anti-SARS-CoV-2 IgG and IgM among Adults over 65 Years Old in the South of Italy
by Immacolata Polvere, Alfredina Parrella, Giovanna Casamassa, Silvia D’Andrea, Annamaria Tizzano, Gaetano Cardinale, Serena Voccola, Piercarmine Porcaro, Romania Stilo, Pasquale Vito and Tiziana Zotti
Diagnostics 2021, 11(3), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11030483 - 09 Mar 2021
Cited by 11 | Viewed by 2030
Abstract
SARS-CoV-2 is a zoonotic betacoronavirus associated with worldwide transmission of COVID-19 disease. By the beginning of March, WHO reported about 113,820,000 confirmed cases including more than 2,527,000 deaths all over the world. However, the true extent of virus circulation or its real infection/fatality [...] Read more.
SARS-CoV-2 is a zoonotic betacoronavirus associated with worldwide transmission of COVID-19 disease. By the beginning of March, WHO reported about 113,820,000 confirmed cases including more than 2,527,000 deaths all over the world. However, the true extent of virus circulation or its real infection/fatality ratio is not well-estimated due to the huge portion of asymptomatic infections. In this observational study, we have estimated the prevalence of specific immunoglobulin M and G directed towards SARS-CoV-2 antigen in a cohort of 1383 adult volunteers aged over 65 years old, living in the district of Benevento, in the South of Italy. Serological screening was carried out on capillary blood in September 2020, seven months after pandemic outbreak in Italy, to evaluate virus circulation and antibody response among elderly adults, in which severe symptoms due to viral infection are more common. The overall seroprevalence of anti-SARS-CoV-2 antibodies was 4.70% (CI 3.70%–5.95%) with no statistically significant differences between sexes. Among these, 69.69% (CI 55.61%–77.80%) tested positive to IgM, 23.08% (CI 14.51%–34.64%) to IgG and 9.23% (CI 4.30%–18.71%) was positive for both. All patients that were positive to IgM underwent molecular testing through RT-qPCR on oral-rhino pharyngeal swabs and only one specimen was positive for SARS-CoV-2 RNA detection. Instead, the presence of IgG from screened volunteers was confirmed by re-testing serum samples using both an ELISA assay validated for in vitro diagnostic use (IVD) and a recently published synthetic peptide-based ELISA assay. In conclusion, our report suggests that (1) early restrictions were successful in limiting COVID-19 diffusion in the district of Benevento; (2) rapid serological analysis is an ideal testing for both determining real seroprevalence and massive screening, whereas detection of viral RNA remains a gold standard for identification of infected patients; (3) even among people without COVID-19 related symptoms, the antibody response against SARS-CoV-2 antigens has individual features. Full article
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