State-of-the-Art SARS-CoV-2 Research in Italy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 33686

Special Issue Editors


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Guest Editor
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38122 Trento, Italy
Interests: virology; cell biology; immunology

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Guest Editor
Viral Pathogenesis and Biosafety Unit, IRCCS-Ospedale San Raffaele, 20132 Milan, Italy
Interests: Zika virus; SARS-CoV-2

Special Issue Information

Dear Colleagues,

Since the emergence of SARS-CoV-2, in February 2020 Italy was the first Western country to be affected by the rapid spread of the virus among the local population, with catastrophic consequences for the death toll, the public health system and for the economy. Accordingly, Italy was also the first nation in Europe to impose and experience the effects of a stringent lockdown. Since then, several laboratories around the country have been investigating the mechanisms of virus replication, the epidemiology of the infection, the cellular and molecular basis of immunity and COVID-19 pathogenesis. In parallel, the scientific community has contributed to improved tools for diagnosis, therapy and prevention.

This special issue focuses on SARS-CoV-2 research in Italy covering a wide range of topics spanning molecular, cellular, epidemiological, computational and clinical aspects which are contributing to our understanding of the pandemic.

Dr. Massimo Pizzato
Dr. Elisa Vicenzi
Guest Editors

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Keywords

  • Viral replication
  • viral pathogenesis
  • immune response
  • vaccines
  • antivirals
  • molecular virology
  • viral genomics
  • viral-host interactions
  • surveillance
  • animal models
  • epidemiology

Published Papers (15 papers)

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17 pages, 2637 KiB  
Article
The Spread of SARS-CoV-2 Omicron Variant in CALABRIA: A Spatio-Temporal Report of Viral Genome Evolution
by Claudia Veneziano, Nadia Marascio, Carmela De Marco, Barbara Quaresima, Flavia Biamonte, Enrico Maria Trecarichi, Gianluca Santamaria, Angela Quirino, Daniele Torella, Aldo Quattrone, Giovanni Matera, Carlo Torti, Caterina De Filippo, Francesco Saverio Costanzo and Giuseppe Viglietto
Viruses 2023, 15(2), 408; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020408 - 31 Jan 2023
Cited by 6 | Viewed by 1632
Abstract
We investigated the evolution of SARS-CoV-2 spread in Calabria, Southern Italy, in 2022. A total of 272 RNA isolates from nasopharyngeal swabs of individuals infected with SARS-CoV-2 were sequenced by whole genome sequencing (N = 172) and/or Sanger sequencing (N = 100). Analysis [...] Read more.
We investigated the evolution of SARS-CoV-2 spread in Calabria, Southern Italy, in 2022. A total of 272 RNA isolates from nasopharyngeal swabs of individuals infected with SARS-CoV-2 were sequenced by whole genome sequencing (N = 172) and/or Sanger sequencing (N = 100). Analysis of diffusion of Omicron variants in Calabria revealed the prevalence of 10 different sub-lineages (recombinant BA.1/BA.2, BA.1, BA.1.1, BA.2, BA.2.9, BA.2.10, BA.2.12.1, BA.4, BA.5, BE.1). We observed that Omicron spread in Calabria presented a similar trend as in Italy, with some notable exceptions: BA.1 disappeared in April in Calabria but not in the rest of Italy; recombinant BA.1/BA.2 showed higher frequency in Calabria (13%) than in the rest of Italy (0.02%); BA.2.9, BA.4 and BA.5 emerged in Calabria later than in other Italian regions. In addition, Calabria Omicron presented 16 non-canonical mutations in the S protein and 151 non-canonical mutations in non-structural proteins. Most non-canonical mutations in the S protein occurred mainly in BA.5 whereas non-canonical mutations in non-structural or accessory proteins (ORF1ab, ORF3a, ORF8 and N) were identified in BA.2 and BA.5 sub-lineages. In conclusion, the data reported here underscore the importance of monitoring the entire SARS-CoV-2 genome. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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8 pages, 904 KiB  
Communication
SARS-CoV-2 and Its Variants in Thrice-Infected Health Workers: A Case Series from an Italian University Hospital
by Maria Grazia Lourdes Monaco, Gianluca Spiteri, Gulser Caliskan, Virginia Lotti, Angela Carta, Davide Gibellini, Giuseppe Verlato and Stefano Porru
Viruses 2022, 14(11), 2536; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112536 - 16 Nov 2022
Cited by 1 | Viewed by 1162
Abstract
Background: We described a SARS-CoV-2 thrice-infected case series in health workers (HW) to evaluate patient and virus variants and lineages and collect information on variables associated with multiple infections. Methods: A retrospective analysis of clinical and laboratory characteristics of SARS-CoV-2 thrice-infected individuals was [...] Read more.
Background: We described a SARS-CoV-2 thrice-infected case series in health workers (HW) to evaluate patient and virus variants and lineages and collect information on variables associated with multiple infections. Methods: A retrospective analysis of clinical and laboratory characteristics of SARS-CoV-2 thrice-infected individuals was carried out in Verona University Hospital, concurrent with the ORCHESTRA project. Variant analysis was conducted on a subset of available specimens. Results: Twelve HW out of 7368 were thrice infected (0.16%). Symptomatic infections were reported in 63.6%, 54.5% and 72.7% of the first, second and third infections, respectively. Nine subjects were fully vaccinated at the time of the third infection, and five had an additional booster dose. The mean time to second infection was 349.6 days (95% CI, 138–443); the mean interval between the second and third infection was 223.5 days (95% CI, 108–530) (p = 0.032). In three cases, the second and third infections were caused by the Omicron variant, but different lineages were detected when the second vs third infections were sequenced. Conclusions: This case series confirms evidence of multiple reinfections with SARS-CoV-2, even from the same variant, in vaccinated HW. These results reinforce the need for continued infection-specific prevention measures in previously infected and reinfected HW. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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16 pages, 3254 KiB  
Article
SARS-CoV-2 in a Mink Farm in Italy: Case Description, Molecular and Serological Diagnosis by Comparing Different Tests
by Ana Moreno, Davide Lelli, Tiziana Trogu, Antonio Lavazza, Ilaria Barbieri, MariaBeatrice Boniotti, Giulia Pezzoni, Cristian Salogni, Stefano Giovannini, Giovanni Alborali, Silvia Bellini, Massimo Boldini, Marco Farioli, Luigi Ruocco, Olivia Bessi, Andrea Maroni Ponti, Ilaria Di Bartolo, Luca De Sabato, Gabriele Vaccari, Gabriele Belli, Alberto Margutti and Maurilio Giorgiadd Show full author list remove Hide full author list
Viruses 2022, 14(8), 1738; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081738 - 08 Aug 2022
Cited by 5 | Viewed by 1735
Abstract
This study described a SARS-CoV-2 infection in minks on an Italian farm. Surveillance was performed based on clinical examination and a collection of 1879 swabs and 74 sera from dead and live animals. The farm was placed under surveillance for 4.5 months, from [...] Read more.
This study described a SARS-CoV-2 infection in minks on an Italian farm. Surveillance was performed based on clinical examination and a collection of 1879 swabs and 74 sera from dead and live animals. The farm was placed under surveillance for 4.5 months, from the end of July 2020, when a man working on the farm tested positive by RT-PCR, till mid-December 2020 when all the animals were sacrificed. Clinical examination revealed no clinical signs or increased mortality rates attributable to SARS-CoV-2, while diagnostic tests detected only four weak PCR-positive samples, but 100% of sera were positive for SARS-CoV-2 anti-S antibodies. The phylogenetic analysis of two SARS-CoV-2 sequences from two minks and the sequence of the worker showed that they belonged to different clades. It could be therefore assumed that two distinct introductions of the virus occurred on the farm, and that the first introduction probably occurred before the start of the surveillance period. From the data collected, and especially from the detection of specific antibodies through the combination of different tests, it can be postulated that syndromic surveillance combined with genome detection by PCR may not be sufficient to achieve a diagnosis in asymptomatic animals. In particular, the serological approach, especially when using tests directed towards the S protein, may be useful for improving the traceability of virus circulation in similar environments. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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16 pages, 1008 KiB  
Article
Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study
by Davide Mangioni, Massimo Oggioni, Liliane Chatenoud, Arianna Liparoti, Sara Uceda Renteria, Laura Alagna, Simona Biscarini, Matteo Bolis, Adriana Di Modugno, Marco Mussa, Giulia Renisi, Riccardo Ungaro, Antonio Muscatello, Andrea Gori, Ferruccio Ceriotti and Alessandra Bandera
Viruses 2022, 14(8), 1683; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081683 - 30 Jul 2022
Cited by 6 | Viewed by 1790
Abstract
Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro [...] Read more.
Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1–Q3 54.5–75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157–309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12–1.77) nmol/L vs. 0.79 (0.63–1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08–1.96) nmol/L vs. 0.66 (0.53–0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79–0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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12 pages, 749 KiB  
Article
Safety of Biologic-DMARDs in Rheumatic Musculoskeletal Disorders: A Population-Based Study over the First Two Waves of COVID-19 Outbreak
by Arianna Sonaglia, Rosanna Comoretto, Enrico Pasut, Elena Treppo, Giulia Del Frate, Donatella Colatutto, Alen Zabotti, Salvatore De Vita and Luca Quartuccio
Viruses 2022, 14(7), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071462 - 01 Jul 2022
Cited by 1 | Viewed by 1580
Abstract
This study aims to explore disease patterns of coronavirus disease (COVID-19) in patients with rheumatic musculoskeletal disorders (RMD) treated with immunosuppressive drugs in comparison with the general population. The observational study considered a cohort of RMD patients treated with biologic drugs or small [...] Read more.
This study aims to explore disease patterns of coronavirus disease (COVID-19) in patients with rheumatic musculoskeletal disorders (RMD) treated with immunosuppressive drugs in comparison with the general population. The observational study considered a cohort of RMD patients treated with biologic drugs or small molecules from September 2019 to November 2020 in the province of Udine, Italy. Data include the assessment of both pandemic waves until the start of the vaccination, between February 2020 and April 2020 (first), and between September 2020 and November 2020 (second). COVID-19 prevalence in 1051 patients was 3.5% without significant differences compared to the general population, and the course of infection was generally benign with 2.6% mortality. A small percentage of COVID-19 positive subjects were treated with low doses of steroids (8%). The most used treatments were represented by anti-TNF agents (65%) and anti-IL17/23 agents (16%). More than two-thirds of patients reported fever, while gastro-intestinal symptoms were recorded in 27% of patients and this clinical involvement was associated with longer swab positivity. The prevalence of COVID-19 in RMD patients has been confirmed as low in both waves. The benign course of COVID-19 in our patients may be linked to the very low number of chronic corticosteroids used and the possible protective effect of anti-TNF agents, which were the main class of biologics herein employed. Gastro-intestinal symptoms might be a predictor of viral persistence in immunosuppressed patients. This finding could be useful to identify earlier COVID-19 carriers with uncommon symptoms, eventually eligible for antiviral drugs. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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13 pages, 281 KiB  
Article
Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients
by Massimo Franchini, Daniele Focosi, Elena Percivalle, Massimiliano Beccaria, Martina Garuti, Omar Arar, Antonietta Pecoriello, Fabio Spreafico, Graziana Greco, Stefano Bertacco, Marco Ghirardini, Tiziana Santini, Michele Schiavulli, Muzzica Stefania, Thaililja Gagliardo, Josè Camilla Sammartino, Alessandro Ferrari, Matteo Zani, Alessia Ballotari, Claudia Glingani and Fausto Baldantiadd Show full author list remove Hide full author list
Viruses 2022, 14(7), 1443; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071443 - 30 Jun 2022
Cited by 6 | Viewed by 1762
Abstract
COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), [...] Read more.
COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients’ median age was 66 years (IQR 50–74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
12 pages, 1639 KiB  
Article
SARS-CoV-2 Circulation during the First Year of the Pandemic: A Seroprevalence Study from January to December 2020 in Tuscany, Italy
by Serena Marchi, Gianvito Lanave, Michele Camero, Francesca Dapporto, Alessandro Manenti, Linda Benincasa, Angela Acciavatti, Giulio Brogi, Simonetta Viviani, Emanuele Montomoli and Claudia Maria Trombetta
Viruses 2022, 14(7), 1441; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071441 - 30 Jun 2022
Cited by 1 | Viewed by 1330
Abstract
Italy was the second country affected by the SARS-CoV-2 pandemic; the virus spread mainly in Northern Italy with a subsequent diffusion to the center and southern part of the country. In this study, we aimed to assess the prevalence of antibodies against SARS-CoV-2 [...] Read more.
Italy was the second country affected by the SARS-CoV-2 pandemic; the virus spread mainly in Northern Italy with a subsequent diffusion to the center and southern part of the country. In this study, we aimed to assess the prevalence of antibodies against SARS-CoV-2 in the general population of the Siena province in the Tuscany region (Central Italy) during 2020. A total of 2480 serum samples collected from January to December 2020 were tested for IgM and IgG antibodies against SARS-CoV-2 by a commercial ELISA. Positive and borderline samples were further tested for the presence of anti-receptor-binding domain (RBD) IgM and IgG antibodies by an in-house ELISA and by a micro-neutralization assay. Out of the 2480 samples tested by the commercial ELISA, 81 (3.3%) were found to be positive or borderline for IgG and 58 (2.3%) for IgM in a total of 133 samples (5.4%) found to be positive or borderline for at least one antibody class. When the commercial ELISA and in-house ELISA/micro-neutralization assay results were combined, 26 samples (1.0%) were positive for RBD IgG, 11 (0.4%) for RBD IgM, and 23 (0.9%) for a neutralizing antibody. An increase in seroprevalence was observed during the year 2020, especially from the end of summer, consistent with the routine epidemiological surveillance of COVID-19 cases. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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18 pages, 1770 KiB  
Article
Nucleopore Traffic Is Hindered by SARS-CoV-2 ORF6 Protein to Efficiently Suppress IFN-β and IL-6 Secretion
by Gianni Gori Savellini, Gabriele Anichini, Claudia Gandolfo and Maria Grazia Cusi
Viruses 2022, 14(6), 1273; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061273 - 11 Jun 2022
Cited by 9 | Viewed by 2861
Abstract
A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins that are able to counteract the host immune system, which is believed to be one of [...] Read more.
A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins that are able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical outcomes. Previous reports demonstrated that the SARS-CoV-2 ORF6 protein strongly suppresses INF-β production by hindering the RIG-I, MDA-5, and MAVS signaling cascade. In the present study, we better characterized the mechanism by which the SARS-CoV-2 ORF6 counteracts IFN-β and interleukin-6 (IL-6), which plays a crucial role in the inflammation process associated with the viral infection. In the present study, we demonstrated that the SARS-CoV-2 ORF6 protein has evolved an alternative mechanism to guarantee host IFN-β and IL-6 suppression, in addition to the transcriptional control exerted on the genes. Indeed, a block in movement through the nucleopore of newly synthetized messenger RNA encoding the immune-modulatory cytokines IFN-β and IL-6 are reported here. The ORF6 accessory protein of SARS-CoV-2 displays a multifunctional activity and may represent one of the most important virulence factors. Where conventional antagonistic strategies of immune evasion—such as the suppression of specific transcription factors (e.g., IRF-3, STAT-1/2)—would not be sufficient, the SARS-CoV-2 ORF6 protein is the trump card for the virus, also blocking the movement of IFN-β and IL-6 mRNAs from nucleus to cytoplasm. Conversely, we showed that nuclear translocation of the NF-κB transcription factor is not affected by the ORF6 protein, although inhibition of its cytoplasmic activation occurred. Therefore, the ORF6 protein exerts a 360-degree inhibition of the antiviral response by blocking as many critical points as possible. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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10 pages, 14236 KiB  
Communication
Effect of Short Time of SARS-CoV-2 Infection in Caco-2 Cells
by Luisa Zupin, Francesco Fontana, Libera Clemente, Maurizio Ruscio, Giuseppe Ricci and Sergio Crovella
Viruses 2022, 14(4), 704; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040704 - 29 Mar 2022
Cited by 9 | Viewed by 2040
Abstract
Coronavirus disease 19 (COVID-19) clinical manifestations include the involvement of the gastrointestinal tract, affecting around 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children. In the present work, the consequence of a short time of viral absorption (5, 15, 30 and 60 [...] Read more.
Coronavirus disease 19 (COVID-19) clinical manifestations include the involvement of the gastrointestinal tract, affecting around 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children. In the present work, the consequence of a short time of viral absorption (5, 15, 30 and 60 min) was tested on the Caco-2 intestinal epithelial cell line. Our findings show that Caco-2 cells are highly permissive to SARS-CoV-2 infection, even after 5 min of viral inoculation at a multiplicity of infection of 0.1. No cytopathic effect was evident during the subsequent 7 days of monitoring; nevertheless, the immunofluorescence staining for the viral nucleocapsid confirmed the presence of intracellular SARS-CoV-2. Our findings highlight the very short time during which SARS-CoV-2 is able to infect these cells in vitro. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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14 pages, 2041 KiB  
Article
Rapid SARS-CoV-2 Intra-Host and Within-Household Emergence of Novel Haplotypes
by Laura Manuto, Marco Grazioli, Andrea Spitaleri, Paolo Fontana, Luca Bianco, Luigi Bertolotti, Martina Bado, Giorgia Mazzotti, Federico Bianca, Francesco Onelia, Giovanni Lorenzin, Fabio Simeoni, Dejan Lazarevic, Elisa Franchin, Claudia Del Vecchio, Ilaria Dorigatti, Giovanni Tonon, Daniela Maria Cirillo, Enrico Lavezzo, Andrea Crisanti and Stefano Toppoadd Show full author list remove Hide full author list
Viruses 2022, 14(2), 399; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020399 - 15 Feb 2022
Cited by 5 | Viewed by 2624
Abstract
In February 2020, the municipality of Vo’, a small town near Padua (Italy) was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. To investigate the viral prevalence and clinical features, the entire population was swab tested in two [...] Read more.
In February 2020, the municipality of Vo’, a small town near Padua (Italy) was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. To investigate the viral prevalence and clinical features, the entire population was swab tested in two sequential surveys. Here we report the analysis of 87 viral genomes, which revealed that the unique ancestor haplotype introduced in Vo’ belongs to lineage B, carrying the mutations G11083T and G26144T. The viral sequences allowed us to investigate the viral evolution while being transmitted within and across households and the effectiveness of the non-pharmaceutical interventions implemented in Vo’. We report, for the first time, evidence that novel viral haplotypes can naturally arise intra-host within an interval as short as two weeks, in approximately 30% of the infected individuals, regardless of symptom severity or immune system deficiencies. Moreover, both phylogenetic and minimum spanning network analyses converge on the hypothesis that the viral sequences evolved from a unique common ancestor haplotype that was carried by an index case. The lockdown extinguished both the viral spread and the emergence of new variants. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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10 pages, 1212 KiB  
Article
A Community Study of SARS-CoV-2 Detection by RT-PCR in Saliva: A Reliable and Effective Method
by Filippo Fronza, Nelli Groff, Angela Martinelli, Beatrice Zita Passerini, Nicolò Rensi, Irene Cortelletti, Nicolò Vivori, Valentina Adami, Anna Helander, Simone Bridi, Michael Pancher, Valentina Greco, Sonia Iolanda Garritano, Elena Piffer, Lara Stefani, Veronica De Sanctis, Roberto Bertorelli, Serena Pancheri, Lucia Collini, Erik Dassi, Alessandro Quattrone, Maria Rosaria Capobianchi, Giancarlo Icardi, Guido Poli, Patrizio Caciagli, Antonio Ferro and Massimo Pizzatoadd Show full author list remove Hide full author list
Viruses 2022, 14(2), 313; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020313 - 02 Feb 2022
Cited by 9 | Viewed by 2870
Abstract
Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given [...] Read more.
Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here, we used a novel saliva collection device designed to favour the safe and correct acquisition of the sample, as well as the processivity of the downstream molecular analysis. We tested 1003 nasopharyngeal swabs and paired saliva samples self-collected by individuals recruited at a public drive-through testing facility. An overall moderate concordance (68%) between the two tests was found, with evidence that neither system can diagnose the infection in 100% of the cases. While the two methods performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent subjects. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study describes a testing strategy of self-collected saliva samples, which is reliable for wide-scale COVID-19 screening in the community and is particularly effective for contact tracing. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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13 pages, 1154 KiB  
Article
Discriminatory Weight of SNPs in Spike SARS-CoV-2 Variants: A Technically Rapid, Unambiguous, and Bioinformatically Validated Laboratory Approach
by Nicolò Musso, Paolo Giuseppe Bonacci, Dafne Bongiorno, Stefano Stracquadanio, Dalida Angela Bivona, Concetta Ilenia Palermo, Guido Scalia, Marco Fichera and Stefania Stefani
Viruses 2022, 14(1), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010123 - 11 Jan 2022
Viewed by 1554
Abstract
Background: The SARS-CoV-2 virus has assumed considerable importance during the COVID-19 pandemic. Its mutation rate is high, involving the spike (S) gene and thus there has been a rapid spread of new variants. Herein, we describe a rapid, easy, adaptable, and affordable workflow [...] Read more.
Background: The SARS-CoV-2 virus has assumed considerable importance during the COVID-19 pandemic. Its mutation rate is high, involving the spike (S) gene and thus there has been a rapid spread of new variants. Herein, we describe a rapid, easy, adaptable, and affordable workflow to uniquely identify all currently known variants through as few analyses. Our method only requires two conventional PCRs of the S gene and two Sanger sequencing reactions, and possibly another PCR/sequencing assay on a N gene portion to identify the B.1.160 lineage. Methods: We selected an S gene 1312 bp portion containing a set of SNPs useful for discriminating all variants. Mathematical, statistical, and bioinformatic analyses demonstrated that our choice allowed us to identify all variants even without looking for all related mutations, as some of them are shared by different variants (e.g., N501Y is found in the Alpha, Beta, and Gamma variants) whereas others, that are more informative, are unique (e.g., A57 distinctive to the Alpha variant). Results: A “weight” could be assigned to each mutation that may be present in the selected portion of the S gene. The method’s robustness was confirmed by analyzing 80 SARS-CoV-2-positive samples. Conclusions: Our workflow identified the variants without the need for whole-genome sequencing and with greater reliability than with commercial kits. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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5 pages, 585 KiB  
Brief Report
Antibody Titer Correlates with Omicron Infection in Vaccinated Healthcare Workers
by Maximiliano Mollura, Riccardo Sarti, Riccardo Levi, Chiara Pozzi, Elena Azzolini, Letterio S. Politi, Alberto Mantovani, Riccardo Barbieri and Maria Rescigno
Viruses 2022, 14(12), 2605; https://0-doi-org.brum.beds.ac.uk/10.3390/v14122605 - 23 Nov 2022
Cited by 2 | Viewed by 1617
Abstract
The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, [...] Read more.
The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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31 pages, 2121 KiB  
Systematic Review
Multisystem Inflammatory Syndrome in Neonates Born to Mothers with SARS-CoV-2 Infection (MIS-N) and in Neonates and Infants Younger Than 6 Months with Acquired COVID-19 (MIS-C): A Systematic Review
by Domenico Umberto De Rose, Flaminia Pugnaloni, Monica Calì, Sara Ronci, Stefano Caoci, Chiara Maddaloni, Ludovica Martini, Alessandra Santisi, Andrea Dotta and Cinzia Auriti
Viruses 2022, 14(4), 750; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040750 - 02 Apr 2022
Cited by 19 | Viewed by 5655
Abstract
(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under [...] Read more.
(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under six months of age, we used a systematic search to retrieve all relevant publications in the field. We screened in PubMed, EMBASE and Scopus for data published until 10 October 2021. (3) Results: Forty-eight articles were considered, including 29 case reports, six case series and 13 cohort studies. Regarding clinical features, only 18.2% of MIS-N neonates presented with fever; differently from older children with MIS-C, in which gastrointestinal symptoms were the most common manifestation, we displayed that cardiovascular dysfunction and respiratory distress are the prevalent findings both in neonates with MIS-N and in neonates/infants with MIS-C. (4) Conclusions: We suggest that all infants with suspected inflammatory disease should undergo echocardiography, due to the possibility of myocardial dysfunction and damage to the coronary arteries observed both in neonates with MIS-N and in neonates/infants with MIS-C. Moreover, we also summarize how they were treated and provide a therapeutic algorithm to suggest best management of these fragile infants. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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9 pages, 257 KiB  
Brief Report
Effects of Casirivimab/Imdevimab Monoclonal Antibody Treatment among Vaccinated Patients Infected by SARS-CoV-2 Delta Variant
by Gaetano Cicchitto, Lorena Cardillo, Claudio de Martinis, Paola Sabatini, Rosita Marchitiello, Giovanna Abate, Adele Rovetti, Antonietta Cavallera, Camillo Apuzzo, Francesco Ferrigno and Giovanna Fusco
Viruses 2022, 14(3), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030650 - 21 Mar 2022
Cited by 11 | Viewed by 2126
Abstract
There is a growing interest in using monoclonal antibodies (mAbs) in the early stages of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection to prevent disease progression. Little is known about the efficacy of mAbs against the delta variant of concern and its [...] Read more.
There is a growing interest in using monoclonal antibodies (mAbs) in the early stages of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection to prevent disease progression. Little is known about the efficacy of mAbs against the delta variant of concern and its clinical presentations. We evaluated the effect of casirivimab/imdevimab treatment among five delta vaccine breakthrough patients. Symptomatic non-hospitalized vaccinated patients were submitted to nasopharyngeal swabs for the detection of SARS-CoV-2 and Next-Generation Sequencing (NGS). Blood analysis and chest Computed Tomography were also performed. A cocktail of casirivimab/imdevimab was administrated, and patients were monitored weekly. Clinical evolution was evaluated by the regression of the symptoms, negative results by real-time RT-PCR, and by the need of hospitalization: these aspects were considered as significant outcomes. In four cases, symptom reversion and viral load reduction were observed within 2 days and 7 days after mAbs treatment, respectively. Only one case, suffering from thymoma, was hospitalized 2 days later because of respiratory failure, which reverted within 18 days. mAbs treatment seems to be safe and effective against the delta variant and its clinical manifestations. Full article
(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Italy)
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