Editor's Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article
Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure
J. Clin. Med. 2021, 10(8), 1599; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081599 - 09 Apr 2021
Cited by 67
Abstract
Background: As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University [...] Read more.
Background: As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Covishield). While the vaccine prevents severe course of and death from COVID-19, the observation of pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns. Objective: To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the “COVID-19 vaccine AstraZeneca”. Methods: Patient files, laboratory findings, and diagnostic imaging results, and endovascular interventions of three concerning patients were evaluated in retrospect. Results: Three women with intracranial venous sinus thrombosis after their first vaccination with “COVID-19 vaccine AstraZeneca” were encountered. Patient #1 was 22 years old and developed headaches four days after the vaccination. On day 7, she experienced a generalized epileptic seizure. Patient #2 was 46 years old. She presented with severe headaches, hemianopia to the right, and mild aphasia 13 days after the vaccination. MRI showed a left occipital intracerebral hemorrhage. Patient #3 was 36 years old and presented 17 days after the vaccination with acute somnolence and right-hand hemiparesis. The three patients were diagnosed with extensive venous sinus thrombosis. They were managed by heparinization and endovascular recanalization of their venous sinuses. They shared similar findings: elevated levels of D-dimers, platelet factor 4 antiplatelet antibodies, corona spike protein antibodies, combined with thrombocytopenia. Under treatment with low-molecular-weight heparin, platelet counts normalized within several days. Conclusion: Early observations insinuate that the exposure to the “COVID-19 vaccine AstraZeneca” might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e.g., intracranial venous sinus thrombosis). These patients’ treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena. Full article
(This article belongs to the Special Issue Stroke Management - Diagnostic and Therapy)
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Article
Prevalence of COVID-19 Vaccine Side Effects among Healthcare Workers in the Czech Republic
J. Clin. Med. 2021, 10(7), 1428; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10071428 - 01 Apr 2021
Cited by 83
Abstract
Background: COVID-19 vaccine side effects have a fundamental role in public confidence in the vaccine and its uptake process. Thus far, the evidence on vaccine safety has exclusively been obtained from the manufacturer-sponsored studies; therefore, this study was designed to provide independent evidence [...] Read more.
Background: COVID-19 vaccine side effects have a fundamental role in public confidence in the vaccine and its uptake process. Thus far, the evidence on vaccine safety has exclusively been obtained from the manufacturer-sponsored studies; therefore, this study was designed to provide independent evidence on Pfizer–BioNTech COVID-19 vaccine side effects. Methods: A cross-sectional survey-based study was carried out between January and February 2021 to collect data on the side effects following the COVID-19 vaccine among healthcare workers in the Czech Republic. The study used a validated questionnaire with twenty-eight multiple-choice items covering the participants’ demographic data, medical anamneses, COVID-19-related anamneses, general, oral, and skin-related side effects. Results: Injection site pain (89.8%), fatigue (62.2%), headache (45.6%), muscle pain (37.1%), and chills (33.9%) were the most commonly reported side effects. All the general side effects were more prevalent among the ≤43-year-old group, and their duration was mainly one day (45.1%) or three days (35.8%) following the vaccine. Antihistamines were the most common drugs associated with side effects, thus requiring further investigation. The people with two doses were generally associated with a higher frequency of side effects. Conclusions: The distribution of side effects among Czech healthcare workers was highly consistent with the manufacturer’s data, especially in terms of their association with the younger age group and the second dose. The overall prevalence of some local and systemic side effects was higher than the manufacturer’s report. Further independent studies on vaccine safety are strongly required to strengthen public confidence in the vaccine. Full article
(This article belongs to the Collection Impact of COVID-19 on the Dental Community)
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Article
The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro
J. Clin. Med. 2021, 10(2), 328; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020328 - 17 Jan 2021
Cited by 71
Abstract
Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) [...] Read more.
Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied. We evaluated three lateral flow assays (RIDA®QUICK SARS-CoV-2 Antigen (R-Biopharm), SARS-CoV-2 Rapid Antigen Test (Roche)), and NADAL® COVID-19 Ag Test (Nal von Minden GmbH, Regensburg, Germany) and one microfluidic immunofluorescence assay (SARS-CoV-2 Ag Test (LumiraDx GmbH, Cologne, Germany)) using 100 clinical samples. Diagnostic rRT-PCR and cell culture testing as a marker for infectivity were performed in parallel. The overall Ag-RDT sensitivity for rRT-PCR-positive samples ranged from 24.3% to 50%. However, for samples with a viral load of more than 6 log10 RNA copies/mL (22/100), typically seen in infectious individuals, Ag-RDT positivity was between 81.8% and 100%. Only 51.6% (33/64) of the rRT-PCR-positive samples were infectious in cell culture. In contrast, three Ag-RDTs demonstrated a more significant correlation with cell culture infectivity (61.8–82.4%). Our findings suggest that large-scale SARS-CoV-2 Ag-RDT-based testing can be considered for detecting potentially infective individuals and reducing the virus spread. Full article
(This article belongs to the Section Infectious Diseases)
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Article
Predicting Perceived Stress Related to the Covid-19 Outbreak through Stable Psychological Traits and Machine Learning Models
J. Clin. Med. 2020, 9(10), 3350; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9103350 - 19 Oct 2020
Cited by 78
Abstract
The global SARS-CoV-2 outbreak and subsequent lockdown had a significant impact on people’s daily lives, with strong implications for stress levels due to the threat of contagion and restrictions to freedom. Given the link between high stress levels and adverse physical and mental [...] Read more.
The global SARS-CoV-2 outbreak and subsequent lockdown had a significant impact on people’s daily lives, with strong implications for stress levels due to the threat of contagion and restrictions to freedom. Given the link between high stress levels and adverse physical and mental consequences, the COVID-19 pandemic is certainly a global public health issue. In the present study, we assessed the effect of the pandemic on stress levels in N = 2053 Italian adults, and characterized more vulnerable individuals on the basis of sociodemographic features and stable psychological traits. A set of 18 psycho-social variables, generalized regressions, and predictive machine learning approaches were leveraged. We identified higher levels of perceived stress in the study sample relative to Italian normative values. Higher levels of distress were found in women, participants with lower income, and participants living with others. Higher rates of emotional stability and self-control, as well as a positive coping style and internal locus of control, emerged as protective factors. Predictive learning models identified participants with high perceived stress, with a sensitivity greater than 76%. The results suggest a characterization of people who are more vulnerable to experiencing high levels of stress during the COVID-19 pandemic. This characterization may contribute to early and targeted intervention strategies. Full article
Article
Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers
J. Clin. Med. 2020, 9(10), 3188; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9103188 - 01 Oct 2020
Cited by 41
Abstract
Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA [...] Read more.
Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length Nucleocapsid protein (N). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in using serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population. Full article
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Article
Psychological Impact of COVID-19 Emergency on Health Professionals: Burnout Incidence at the Most Critical Period in Spain
J. Clin. Med. 2020, 9(9), 3029; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9093029 - 20 Sep 2020
Cited by 49
Abstract
Background: The health profession is a burnout producer due to the continuous contact with pain and suffering. In addition, excessive workloads can generate stress and psychological distress. Objectives: The aim of this study was to determine the degree of burnout and its main [...] Read more.
Background: The health profession is a burnout producer due to the continuous contact with pain and suffering. In addition, excessive workloads can generate stress and psychological distress. Objectives: The aim of this study was to determine the degree of burnout and its main triggers in health professionals in Spain at the most critical period of the COVID-19 emergency. Method: A quantitative research was developed through a simple random sampling in different Spanish hospitals through the period of greatest impact of the pandemic (N = 157). Data were collected using a standardized questionnaire from Maslach burnout inventory (MBI) containing 22 items, which measures three subscales: emotional burnout, depersonalization, and self-fulfillment. Results: depersonalization values reached 38.9%. A total of 90.4% of the health professionals considered that psychological care should be provided from the work centers. Furthermore, 43.3% of the health professionals estimated that they might need psychological treatment in the future. Finally, 85.4% stated that the lack of personal protective equipment (PPE) generated an increase in stress and anxiety. Conclusion: This study demonstrates the need to consider specific mental health care services and training in crises to avoid possible psychological disorders. The information obtained is also valuable for the development of future prevention protocols and training of health personnel to face pandemics of these characteristics or emergency scenarios. Having the necessary physical means for their protection, as well to updated regular and accurate information, is essential to avoid feelings of fear and uncertainty. This would promote the health of these professionals. Full article
Article
Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors
J. Clin. Med. 2020, 9(9), 2780; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092780 - 27 Aug 2020
Cited by 46
Abstract
We aimed to assess the prevalence of and factors associated with anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in a large population of adult volunteers from five administrative departments of the Liguria and Lombardia regions. A total of 3609 individuals were included [...] Read more.
We aimed to assess the prevalence of and factors associated with anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in a large population of adult volunteers from five administrative departments of the Liguria and Lombardia regions. A total of 3609 individuals were included in this analysis. Participants were tested for anti-SARS-CoV-2 antibodies [Immunoglobulin G (IgG) and M (IgM) class antibodies] at three private laboratories (Istituto Diganostico Varelli, Medical Center, and Casa della Salute di Genova). Demographic data, occupational or private exposure to SARS-CoV-2-infected patients, and prior medical history consistent with SARS-CoV-2 infection were collected according to a preplanned analysis. The overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0% [398/3609; confidence interval (CI) 10.0%–12.1%]. Seroprevalence was higher in female inmates than in male inmates (12.5% vs. 9.2%, respectively, p = 0.002), with the highest rate observed among adults aged >55 years (13.2%). A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59–3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19–6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75–6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94–88.71, p = 0.001). In conclusion, we found a high prevalence (11.0%) of SARS-CoV-2 infection that is significantly associated with residing in long-term care facilities or occupational exposure to the virus. These findings warrant further investigation into SARS-CoV-2 antibody prevalence among the Italian population. Full article
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Article
Antimicrobial Stewardship Program, COVID-19, and Infection Control: Spread of Carbapenem-Resistant Klebsiella Pneumoniae Colonization in ICU COVID-19 Patients. What Did Not Work?
J. Clin. Med. 2020, 9(9), 2744; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092744 - 25 Aug 2020
Cited by 48
Abstract
The Italian burden of disease associated with infections due to antibiotic-resistant bacteria has been very high, largely attributed to Carbapenem-Resistant Klebsiella pneumoniae (CR-Kp). The implementation of infection control measures and antimicrobial stewardship programs (ASP) has been shown to reduce healthcare-related infections [...] Read more.
The Italian burden of disease associated with infections due to antibiotic-resistant bacteria has been very high, largely attributed to Carbapenem-Resistant Klebsiella pneumoniae (CR-Kp). The implementation of infection control measures and antimicrobial stewardship programs (ASP) has been shown to reduce healthcare-related infections caused by multidrug resistance (MDR) germs. Since 2016, in our teaching hospital of Terni, an ASP has been implemented in an intensive care unit (ICU) setting, with the “daily-ICU round strategy” and particular attention to infection control measures. We performed active surveillance for search patients colonized by Carbapenem-Resistant Enterobacteriaceae (CRE). In March 2020, coronavirus disease 2019 (COVID-19) arrived and the same ICU was reserved only for COVID-19 patients. In our retrospective observational study, we analyzed the bimonthly incidence of CRE colonization patients and the incidence of CRE acquisition in our ICU during the period of January 2019 to June 2020. In consideration of the great attention and training of all staff on infection control measures in the COVID-19 era, we would have expected a clear reduction in CRE acquisition, but this did not happen. In fact, the incidence of CRE acquisition went from 6.7% in 2019 to 50% in March–April 2020. We noted that 67% of patients that had been changed in posture with prone position were colonized by CRE, while only 37% of patients that had not been changed in posture were colonized by CRE. In our opinion, the high intensity of care, the prone position requiring 4–5 healthcare workers (HCWs), equipped with personal protective equipment (PPE) in a high risk area, with extended and prolonged contact with the patient, and the presence of 32 new HCWs from other departments and without work experience in the ICU setting, contributed to the spread of CR-Kp in our ICU, determining an increase in CRE acquisition colonization. Full article
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Article
Mental Health of Medical and Non-Medical Professionals during the Peak of the COVID-19 Pandemic: A Cross-Sectional Nationwide Study
J. Clin. Med. 2020, 9(8), 2527; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082527 - 05 Aug 2020
Cited by 46
Abstract
Background: The study aimed to compare psychopathological expressions during the COVID-19 (novel coronavirus disease 2019) pandemic, as declared on March 11th 2020 by the World Health Organization, with respect to which institutional variables might distinguish the impact of COVID-19 in medical and non-medical [...] Read more.
Background: The study aimed to compare psychopathological expressions during the COVID-19 (novel coronavirus disease 2019) pandemic, as declared on March 11th 2020 by the World Health Organization, with respect to which institutional variables might distinguish the impact of COVID-19 in medical and non-medical professionals. Methods: A cross-sectional study was performed nationwide between 16th March and the 26th April 2020 in Poland. A total of 2039 respondents representing all healthcare providers (59.8%) as well as other professionals filled in the sociodemographic section, the General Health Questionnaire-28 and the author’s questionnaire with questions related to exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the availability of protective measures, quarantine, change of working hours and place of employment during the pandemic, as well as feelings associated with the state of the pandemic. Results: Medical professionals more often presented with relevant psychopathological symptoms (GHQ-28 (General Health Questionnaire-28) total score >24) than the non-medical group (60.8% vs. 48.0%, respectively) such as anxiety, insomnia and somatic symptoms even after adjustment for potential confounding factors. Male sex, older age and appropriate protective equipment were associated with significantly lower GHQ-28 total scores in medical professionals, whereas among non-medical professionals, male sex was associated with significantly lower GHQ-28 total scores. Conclusions: Somatic and anxiety symptoms as well as insomnia are more prevalent among medical staff than workers in other professions. Targeting the determinants of these differences should be included in interventions aimed at restoring psychological well-being in this specific population. Apparently, there are present gender differences in psychological responses that are independent of profession. Full article
Article
Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis
J. Clin. Med. 2020, 9(8), 2489; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082489 - 03 Aug 2020
Cited by 59
Abstract
Background: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among [...] Read more.
Background: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. Methods: A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. Results: A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I2 = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I2 = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I2 = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I2 = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). Conclusions: The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets. Full article
(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)
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Article
Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection
J. Clin. Med. 2020, 9(8), 2429; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082429 - 29 Jul 2020
Cited by 69
Abstract
Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective [...] Read more.
Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739–7.995), p = 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio > 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Article
Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients
J. Clin. Med. 2020, 9(7), 2268; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072268 - 17 Jul 2020
Cited by 61
Abstract
Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, [...] Read more.
Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). Conclusions: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Article
HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration
J. Clin. Med. 2020, 9(7), 2217; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072217 - 13 Jul 2020
Cited by 45
Abstract
Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. [...] Read more.
Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient’s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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Article
The Enemy Which Sealed the World: Effects of COVID-19 Diffusion on the Psychological State of the Italian Population
J. Clin. Med. 2020, 9(6), 1802; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061802 - 10 Jun 2020
Cited by 84
Abstract
Background: Starting from the first months of 2020, worldwide population has been facing the COVID-19 pandemic. Many nations, including Italy, took extreme actions to reduce the diffusion of the virus, profoundly changing lifestyles. The Italians have been faced with both the fear of [...] Read more.
Background: Starting from the first months of 2020, worldwide population has been facing the COVID-19 pandemic. Many nations, including Italy, took extreme actions to reduce the diffusion of the virus, profoundly changing lifestyles. The Italians have been faced with both the fear of contracting the infection and the consequences of enforcing social distancing. This study was aimed to understand the psychological impact of the COVID-19 outbreak and the psychopathological outcomes related to the first phase of this emergency. Methods: The study included 2291 respondents. An online survey collected information on socio-demographic variables, history of direct or indirect contact with COVID-19, and additional information concerning the COVID-19 emergency. Moreover, psychopathological symptoms such as anxiety, mood alterations and post-traumatic symptomatology were assessed. Results: The results revealed that respectively 31.38%, 37.19% and 27.72% of respondents reported levels of general psychopathological symptomatology, anxiety, and PTSD symptoms over the cut-off scores. Furthermore, a significant worsening of mood has emerged. Being a female or under the age of 50 years, having had direct contact with people infected by the COVID-19, and experiencing uncertainty about the risk of contagion represent risk factors for psychological distress. Conclusions: Our findings indicate that the first weeks of the COVID-19 pandemic appear to impact not only on physical health but also on psychological well-being. Although these results need to be considered with caution being based on self-reported data collected at the beginning of this emergency, they should be used as a starting point for further studies aimed to develop interventions to minimize both the brief and long-term psychological consequences of the COVID-19 pandemic. Full article
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Article
A Cohort of Patients with COVID-19 in a Major Teaching Hospital in Europe
J. Clin. Med. 2020, 9(6), 1733; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061733 - 04 Jun 2020
Cited by 143
Abstract
Background: Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to [...] Read more.
Background: Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. Methods: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered into an electronic case report form, which was monitored prior to the analysis. Results: We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients’ median age was 61 years, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The overall mortality was 20.7% and was higher in men (26.6% vs. 15.1%). Seventy-five patients with a final outcome were transferred to the intensive care unit (ICU) (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. Conclusions: We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Article
Using Machine Learning to Predict ICU Transfer in Hospitalized COVID-19 Patients
J. Clin. Med. 2020, 9(6), 1668; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061668 - 01 Jun 2020
Cited by 56
Abstract
Objectives: Approximately 20–30% of patients with COVID-19 require hospitalization, and 5–12% may require critical care in an intensive care unit (ICU). A rapid surge in cases of severe COVID-19 will lead to a corresponding surge in demand for ICU care. Because of constraints [...] Read more.
Objectives: Approximately 20–30% of patients with COVID-19 require hospitalization, and 5–12% may require critical care in an intensive care unit (ICU). A rapid surge in cases of severe COVID-19 will lead to a corresponding surge in demand for ICU care. Because of constraints on resources, frontline healthcare workers may be unable to provide the frequent monitoring and assessment required for all patients at high risk of clinical deterioration. We developed a machine learning-based risk prioritization tool that predicts ICU transfer within 24 h, seeking to facilitate efficient use of care providers’ efforts and help hospitals plan their flow of operations. Methods: A retrospective cohort was comprised of non-ICU COVID-19 admissions at a large acute care health system between 26 February and 18 April 2020. Time series data, including vital signs, nursing assessments, laboratory data, and electrocardiograms, were used as input variables for training a random forest (RF) model. The cohort was randomly split (70:30) into training and test sets. The RF model was trained using 10-fold cross-validation on the training set, and its predictive performance on the test set was then evaluated. Results: The cohort consisted of 1987 unique patients diagnosed with COVID-19 and admitted to non-ICU units of the hospital. The median time to ICU transfer was 2.45 days from the time of admission. Compared to actual admissions, the tool had 72.8% (95% CI: 63.2–81.1%) sensitivity, 76.3% (95% CI: 74.7–77.9%) specificity, 76.2% (95% CI: 74.6–77.7%) accuracy, and 79.9% (95% CI: 75.2–84.6%) area under the receiver operating characteristics curve. Conclusions: A ML-based prediction model can be used as a screening tool to identify patients at risk of imminent ICU transfer within 24 h. This tool could improve the management of hospital resources and patient-throughput planning, thus delivering more effective care to patients hospitalized with COVID-19. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Article
Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy
J. Clin. Med. 2020, 9(5), 1548; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051548 - 20 May 2020
Cited by 79
Abstract
We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with [...] Read more.
We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802–0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Article
Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site
J. Clin. Med. 2020, 9(5), 1473; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051473 - 14 May 2020
Cited by 46
Abstract
An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially [...] Read more.
An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an “up” and “down” state. In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses. Full article
(This article belongs to the Section Infectious Diseases)
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Article
Clotting Factors in COVID-19: Epidemiological Association and Prognostic Values in Different Clinical Presentations in an Italian Cohort
J. Clin. Med. 2020, 9(5), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051371 - 07 May 2020
Cited by 47
Abstract
Introduction: A novel highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19) outbreak, which has spread rapidly from China to other countries. Little is known about laboratory [...] Read more.
Introduction: A novel highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19) outbreak, which has spread rapidly from China to other countries. Little is known about laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the basic clotting parameters in COVID-19 patients and their prognostic role in different clinical forms of the disease. Material and Methods: We enrolled 67 COVID-19 patients admitted to the Emergency Department. A cohort of 67 age- and sex-matched non-COVID-19 patients with acute respiratory illness was used as a control group. For all patients, platelet count (PLT), prothrombin time (PT), activated thromboplastin time (aPTT), C-reactive protein (PCR), fibrinogen, and D-dimer were determined. The COVID-19 population was divided in two groups according to the presence or absence of SARS. The clotting factors values were compared between the groups. Results: At admission, the COVID-19 patients showed statistically significant increased levels of fibrinogen (601.5 (480–747) vs. 455 (352.5–588.5) mg/dL; p = 0.0000064), and a higher percentage of patients had fibrinogen levels >400 mg/dL (86% vs.58%; p = 0.0054) compared to the control group. The levels of fibrinogen were higher in COVID-19 patients with SARS compared to those without SARS (747 (600.0–834.0) vs. 567 (472.5–644.50); p = 0.0003). Conclusion: Fibrinogen seems to increase early in COVID-19 patients and may be used as a risk stratification marker for the early detection of a subgroup of COVID-19 patient at increased risk to develop SARS, who might benefit from a different and thorough clinical surveillance and treatment. Full article
(This article belongs to the Section Vascular Medicine)
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Article
Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomized Controlled Trials
J. Clin. Med. 2020, 9(4), 1129; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9041129 - 15 Apr 2020
Cited by 40
Abstract
The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among [...] Read more.
The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61–0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59–0.91; BR: HR 0.51 95% CI 0.28–0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61–0.98; chemotherapy alone: HR 0.68, 95% CI 0.54–0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82–1.04, I2 = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18–1.93, I2 = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47–2.91, I2 = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen. Full article
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Article
Master Regulator Analysis of the SARS-CoV-2/Human Interactome
J. Clin. Med. 2020, 9(4), 982; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9040982 - 01 Apr 2020
Cited by 95
Abstract
The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we [...] Read more.
The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus. Full article
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Article
People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy
J. Clin. Med. 2020, 9(4), 965; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9040965 - 31 Mar 2020
Cited by 211
Abstract
The coronavirus disease 2019 (COVID-19) epidemic affects people’s health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted [...] Read more.
The coronavirus disease 2019 (COVID-19) epidemic affects people’s health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants’ characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, −7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic. Full article
Article
Evaluation of the Dimensional Accuracy of 3D-Printed Anatomical Mandibular Models Using FFF, SLA, SLS, MJ, and BJ Printing Technology
J. Clin. Med. 2020, 9(3), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030817 - 17 Mar 2020
Cited by 66
Abstract
With the rapid progression of additive manufacturing and the emergence of new 3D printing technologies, accuracy assessment is mostly being performed on isosymmetric-shaped test bodies. However, the accuracy of anatomic models can vary. The dimensional accuracy of root mean square values in terms [...] Read more.
With the rapid progression of additive manufacturing and the emergence of new 3D printing technologies, accuracy assessment is mostly being performed on isosymmetric-shaped test bodies. However, the accuracy of anatomic models can vary. The dimensional accuracy of root mean square values in terms of trueness and precision of 50 mandibular replicas, printed with five common printing technologies, were evaluated. The highest trueness was found for the selective laser sintering printer (0.11 ± 0.016 mm), followed by a binder jetting printer (0.14 ± 0.02 mm), and a fused filament fabrication printer (0.16 ± 0.009 mm). However, highest precision was identified for the fused filament fabrication printer (0.05 ± 0.005 mm) whereas other printers had marginally lower values. Despite the statistically significance (p < 0.001), these differences can be considered clinically insignificant. These findings demonstrate that all 3D printing technologies create models with satisfactory dimensional accuracy for surgical use. Since satisfactory results in terms of accuracy can be reached with most technologies, the choice should be more strongly based on the printing materials, the intended use, and the overall budget. The simplest printing technology (fused filament fabrication) always scored high and thus is a reliable choice for most purposes. Full article
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Article
Prediction of the Epidemic Peak of Coronavirus Disease in Japan, 2020
J. Clin. Med. 2020, 9(3), 789; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030789 - 13 Mar 2020
Cited by 132
Abstract
The first case of coronavirus disease 2019 (COVID-19) in Japan was reported on 15 January 2020 and the number of reported cases has increased day by day. The purpose of this study is to give a prediction of the epidemic peak for COVID-19 [...] Read more.
The first case of coronavirus disease 2019 (COVID-19) in Japan was reported on 15 January 2020 and the number of reported cases has increased day by day. The purpose of this study is to give a prediction of the epidemic peak for COVID-19 in Japan by using the real-time data from 15 January to 29 February 2020. Taking into account the uncertainty due to the incomplete identification of infective population, we apply the well-known SEIR compartmental model for the prediction. By using a least-square-based method with Poisson noise, we estimate that the basic reproduction number for the epidemic in Japan is R 0 = 2.6 ( 95 % CI, 2.4 2.8 ) and the epidemic peak could possibly reach the early-middle summer. In addition, we obtain the following epidemiological insights: (1) the essential epidemic size is less likely to be affected by the rate of identification of the actual infective population; (2) the intervention has a positive effect on the delay of the epidemic peak; (3) intervention over a relatively long period is needed to effectively reduce the final epidemic size. Full article
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Article
Optimization Method for Forecasting Confirmed Cases of COVID-19 in China
J. Clin. Med. 2020, 9(3), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030674 - 02 Mar 2020
Cited by 175
Abstract
In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. [...] Read more.
In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. In the current study, we present a new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China. The proposed model is an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA). In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances. Full article
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Article
Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19)
J. Clin. Med. 2020, 9(2), 601; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020601 - 24 Feb 2020
Cited by 99
Abstract
The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to [...] Read more.
The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout. Full article
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Article
Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020
J. Clin. Med. 2020, 9(2), 596; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020596 - 22 Feb 2020
Cited by 105
Abstract
The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of [...] Read more.
The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down. Full article
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Article
Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China
J. Clin. Med. 2020, 9(2), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020571 - 19 Feb 2020
Cited by 146
Abstract
We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the [...] Read more.
We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing. Full article
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Article
Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data
J. Clin. Med. 2020, 9(2), 538; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020538 - 17 Feb 2020
Cited by 605
Abstract
The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the [...] Read more.
The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk. Full article
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Article
Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases
J. Clin. Med. 2020, 9(2), 523; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020523 - 14 Feb 2020
Cited by 210
Abstract
The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand [...] Read more.
The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data. Full article
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Article
Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations
J. Clin. Med. 2020, 9(2), 498; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020498 - 11 Feb 2020
Cited by 100
Abstract
The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has [...] Read more.
The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic. Full article
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Article
Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions
J. Clin. Med. 2020, 9(2), 462; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020462 - 07 Feb 2020
Cited by 709
Abstract
Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the [...] Read more.
Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction. Full article
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Article
Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak
J. Clin. Med. 2020, 9(2), 388; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020388 - 01 Feb 2020
Cited by 248
Abstract
Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from [...] Read more.
Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403–540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18–25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49–2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation. Full article
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Article
Evaluation of Transfer Learning with Deep Convolutional Neural Networks for Screening Osteoporosis in Dental Panoramic Radiographs
J. Clin. Med. 2020, 9(2), 392; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020392 - 01 Feb 2020
Cited by 52
Abstract
Dental panoramic radiographs (DPRs) provide information required to potentially evaluate bone density changes through a textural and morphological feature analysis on a mandible. This study aims to evaluate the discriminating performance of deep convolutional neural networks (CNNs), employed with various transfer learning strategies, [...] Read more.
Dental panoramic radiographs (DPRs) provide information required to potentially evaluate bone density changes through a textural and morphological feature analysis on a mandible. This study aims to evaluate the discriminating performance of deep convolutional neural networks (CNNs), employed with various transfer learning strategies, on the classification of specific features of osteoporosis in DPRs. For objective labeling, we collected a dataset containing 680 images from different patients who underwent both skeletal bone mineral density and digital panoramic radiographic examinations at the Korea University Ansan Hospital between 2009 and 2018. Four study groups were used to evaluate the impact of various transfer learning strategies on deep CNN models as follows: a basic CNN model with three convolutional layers (CNN3), visual geometry group deep CNN model (VGG-16), transfer learning model from VGG-16 (VGG-16_TF), and fine-tuning with the transfer learning model (VGG-16_TF_FT). The best performing model achieved an overall area under the receiver operating characteristic of 0.858. In this study, transfer learning and fine-tuning improved the performance of a deep CNN for screening osteoporosis in DPR images. In addition, using the gradient-weighted class activation mapping technique, a visual interpretation of the best performing deep CNN model indicated that the model relied on image features in the lower left and right border of the mandibular. This result suggests that deep learning-based assessment of DPR images could be useful and reliable in the automated screening of osteoporosis patients. Full article
(This article belongs to the Special Issue Clinical Medicine for Healthcare and Sustainability)
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Editorial

Editorial
Cholesterol in Relation to COVID-19: Should We Care about It?
J. Clin. Med. 2020, 9(6), 1909; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061909 - 18 Jun 2020
Cited by 66
Abstract
Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular [...] Read more.
Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol-lowering therapies in reducing viral infectivity. In addition to their lipid-lowering and plaque-stabilisation effects, statins possess pleiotropic effects including anti-inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID-19. Full article
(This article belongs to the Section Cardiology)
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Editorial
COVID-19: A Recommendation to Examine the Effect of Mouthrinses with β-Cyclodextrin Combined with Citrox in Preventing Infection and Progression
J. Clin. Med. 2020, 9(4), 1126; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9041126 - 15 Apr 2020
Cited by 76
Abstract
Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on [...] Read more.
Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on the market have ingredients that could contribute to lower the SARS-CoV-2 viral load, and thus facilitate the fight against oral transmission. If chlorhexidine, a usual component of mouth rinse, is not efficient to kill SARS-CoV-2, the use of a mouth rinses and/or with local nasal applications that contain β-cyclodextrins combined with flavonoids agents, such as Citrox, could provide valuable adjunctive treatment to reduce the viral load of saliva and nasopharyngeal microbiota, including potential SARS-CoV-2 carriage. We urge national agencies and authorities to start clinical trials to evaluate the preventive effects of βCD-Citrox therapeutic oral biofilm rinses in reducing the viral load of the infection and possibly disease progression. Full article
(This article belongs to the Special Issue The Oral Microbiome in Health and Disease)

Review

Review
Coronary Microvascular Dysfunction
J. Clin. Med. 2020, 9(9), 2880; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092880 - 06 Sep 2020
Cited by 51
Abstract
Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has [...] Read more.
Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. Impairment of this mechanism, defined as coronary microvascular dysfunction (CMD), carries an increased risk of adverse cardiovascular clinical outcomes. Coronary endothelial dysfunction accounts for approximately two-thirds of clinical conditions presenting with symptoms and signs of myocardial ischemia without obstructive coronary disease, termed “ischemia with non-obstructive coronary artery disease” (INOCA) and for a small proportion of “myocardial infarction with non-obstructive coronary artery disease” (MINOCA). More frequently, the clinical presentation of INOCA is microvascular angina due to CMD, while some patients present vasospastic angina due to epicardial spasm, and mixed epicardial and microvascular forms. CMD may be associated with focal and diffuse epicardial coronary atherosclerosis, which may reinforce each other. Both INOCA and MINOCA are more common in females. Clinical classification of CMD includes the association with conditions in which atherosclerosis has limited relevance, with non-obstructive atherosclerosis, and with obstructive atherosclerosis. Several studies already exist which support the evidence that CMD is part of systemic microvascular disease involving multiple organs, such as brain and kidney. Moreover, CMD is strongly associated with the development of heart failure with preserved ejection fraction (HFpEF), diabetes, hypertensive heart disease, and also chronic inflammatory and autoimmune diseases. Since coronary microcirculation is not visible on invasive angiography or computed tomographic coronary angiography (CTCA), the diagnosis of CMD is usually based on functional assessment of microcirculation, which can be performed by both invasive and non-invasive methods, including the assessment of delayed flow of contrast during angiography, measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), evaluation of angina induced by intracoronary acetylcholine infusion, and assessment of myocardial perfusion by positron emission tomography (PET) and magnetic resonance (CMR). Full article
(This article belongs to the Section Cardiology)
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Review
COVID-19 and Obesity: Dangerous Liaisons
J. Clin. Med. 2020, 9(8), 2511; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082511 - 04 Aug 2020
Cited by 64
Abstract
Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe [...] Read more.
Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe symptoms and negative prognosis. Remarkably, the severity of COVID-19 appears to rise with increasing body mass index (BMI). The association between COVID-19 outcomes and overweight/obesity has biological and physiological plausibility. Potential pathophysiological mechanisms that may explain this strong association include the chronic pro-inflammatory state, the excessive oxidative stress response, and the impaired immunity that is commonly reported in these individuals. The role of cytokines, mammalian target of rapamycin (mTOR), and altered natural killer cell polarization in the dangerous liaison between COVID-19 and obesity are discussed here. These pathways can favor and accelerate the deleterious downstream cellular effects of SARS-CoV-2. Moreover, obesity is well known to be associated with reduced lung function and poor response to mechanical ventilation, thus placing these individuals at high risk of severe illness and mortality from COVID-19. Furthermore, obesity may lead to other complications, such as renal failure, cardiovascular dysfunction, hypertension, and vascular damage, which in turn can further accelerate negative clinical outcomes from COVID-19. Obese individuals should be shielded against any potential viral exposure to SARS-CoV-2 with consequential considerations for compulsory protection devices and social distancing. Health care providers should be aware that obesity predisposes to severe symptoms and negative prognosis in COVID-19 patients. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Review
Racial Disparities-Associated COVID-19 Mortality among Minority Populations in the US
J. Clin. Med. 2020, 9(8), 2442; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082442 - 30 Jul 2020
Cited by 101
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus that causes the novel coronavirus disease 2019 (COVID-19), is highly transmissible and pathogenic for humans and may cause life-threatening disease and mortality, especially in individuals with underlying comorbidities. First identified in an outbreak in [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus that causes the novel coronavirus disease 2019 (COVID-19), is highly transmissible and pathogenic for humans and may cause life-threatening disease and mortality, especially in individuals with underlying comorbidities. First identified in an outbreak in Wuhan, China, COVID-19 is affecting more than 185 countries and territories around the world, with more than 15,754,651 confirmed cases and more than 640,029 deaths. Since December 2019, SARS-CoV-2 transmission has become a global threat, which includes confirmed cases in all 50 states within the United States (US). As of 25 July 2020, the Johns Hopkins Whiting School of Engineering Center for Systems Science and Engineering reports more than 4,112,651 cases and 145,546 deaths. To date, health disparities are associated with COVID-19 mortality among underserved populations. Here, the author explores potential underlying reasons for reported disproportionate, increased risks of mortality among African Americans and Hispanics/Latinos with COVID-19 compared with non-Hispanic Whites. The author examines the underlying clinical implications that may predispose minority populations and the adverse clinical outcomes that may contribute to increased risk of mortality. Government and community-based strategies to safeguard minority populations at risk for increased morbidity and mortality are essential. Underserved populations living in poverty with limited access to social services across the US are more likely to have underlying medical conditions and are among the most vulnerable. Societal and cultural barriers for ethnic minorities to achieve health equity are systemic issues that may be addressed only through shifts in governmental policies, producing long-overdue, substantive changes to end health care inequities. Full article
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Review
Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update
J. Clin. Med. 2020, 9(8), 2359; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082359 - 23 Jul 2020
Cited by 50
Abstract
The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of [...] Read more.
The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population. Full article
(This article belongs to the Special Issue Atherosclerosis: Endothelial Dysfunction and Beyond)
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Review
New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges
J. Clin. Med. 2020, 9(7), 2222; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072222 - 13 Jul 2020
Cited by 46
Abstract
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 (SMN1) gene and a [...] Read more.
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequent decrease in the SMN protein leading to lower motor neuron degeneration. Recently, Food and Drug Administration (FDA) and European Medical Agency (EMA) approved the antisense oligonucleotide nusinersen, the first SMA disease-modifying treatment and gene replacement therapy by onasemnogene abeparvovec. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. However, the availability of effective approaches has raised up ethical, medical and financial issues that are routinely faced by the SMA community. This review covers the available data and the new challenges of SMA therapeutic strategies. Full article
(This article belongs to the Special Issue Innovative Therapies in Neuromuscular Diseases)
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Review
Frailty and COVID-19: A Systematic Scoping Review
J. Clin. Med. 2020, 9(7), 2106; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072106 - 04 Jul 2020
Cited by 54
Abstract
Older people have paid a huge toll in terms of mortality during the coronavirus disease-19 (COVID-19) pandemic. Frailty may have contributed to the vulnerability of older people to more severe clinical presentation. We aimed at reviewing available evidence about frailty and COVID-19. We [...] Read more.
Older people have paid a huge toll in terms of mortality during the coronavirus disease-19 (COVID-19) pandemic. Frailty may have contributed to the vulnerability of older people to more severe clinical presentation. We aimed at reviewing available evidence about frailty and COVID-19. We searched PUBMED, Web of Science, and EMBASE from 1 December 2019 to 29 May 2020. Study selection and data extraction were performed by three independent reviewers. Qualitative synthesis was conducted and quantitative data extracted when available. Forty papers were included: 13 editorials, 15 recommendations/guidelines, 3 reviews, 1 clinical trial, 6 observational studies, 2 case reports. Editorials and reviews underlined the potential clinical relevance of assessing frailty among older patients with COVID-19. However, frailty was only investigated in regards to its association with overall mortality, hospital contagion, intensive care unit admission rates, and disease phenotypes in the few observational studies retrieved. Specific interventions in relation to frailty or its impact on COVID-19 treatments have not been evaluated yet. Even with such limited evidence, clinical recommendations on the use of frailty tools have been proposed to support decision making about escalation plan. Ongoing initiatives are expected to improve knowledge of COVID-19 interaction with frailty and to promote patient-centered approaches. Full article
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Review
Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development
J. Clin. Med. 2020, 9(6), 2004; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9062004 - 26 Jun 2020
Cited by 68
Abstract
Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets the disease source at the RNA level and offers a promising alternative to [...] Read more.
Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets the disease source at the RNA level and offers a promising alternative to therapies targeting downstream processes. To translate ASO-based therapies into a clinical success, it is crucial to overcome the challenges associated with off-target side effects and insufficient biological activity. In this regard, several chemical modifications and diverse delivery strategies have been explored. In this review, we systematically discuss the chemical modifications, mechanism of action, and optimized delivery strategies of several different classes of ASOs. Further, we highlight the recent advances made in development of ASO-based drugs with a focus on drugs that are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for clinical applications. We also discuss various promising ASO-based drug candidates in the clinical trials, and the outstanding opportunity of emerging microRNA as a viable therapeutic target for future ASO-based therapies. Full article
(This article belongs to the Section Pharmacology)
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Review
COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection
J. Clin. Med. 2020, 9(6), 1917; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061917 - 19 Jun 2020
Cited by 72
Abstract
In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on [...] Read more.
In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients’ quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment. Full article
(This article belongs to the Section Pulmonology)
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Review
Available Technologies, Applications and Benefits of Teleorthodontics. A Literature Review and Possible Applications during the COVID-19 Pandemic
J. Clin. Med. 2020, 9(6), 1891; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061891 - 17 Jun 2020
Cited by 46
Abstract
Background: COVID-2019 spread rapidly throughout the world from China. This infection is highly contagiousness, has a high morbidity, and is capable of evolving into a potentially lethal form of interstitial pneumonia. Numerous countries shut-down various activities that were considered “not essential.” Dental treatment [...] Read more.
Background: COVID-2019 spread rapidly throughout the world from China. This infection is highly contagiousness, has a high morbidity, and is capable of evolving into a potentially lethal form of interstitial pneumonia. Numerous countries shut-down various activities that were considered “not essential.” Dental treatment was in this category and, at the time of writing, only non-deferrable emergencies are still allowed in many countries. Therefore, follow-up visits of ongoing active therapies (e.g., orthodontic treatment) must be handled taking special precautions. This literature review aims at reducing in-office appointments by providing an overview of the technologies available and their reliability in the long-distance monitoring of patients, i.e., teledentistry. Methods: A literature review was made according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Randomized clinical trials, cross sectional, observational, and case-control studies were evaluated with the Mixed Methods Appraisal Tool for quality assessment and study limitations. Results: A primary search found 80 articles, 69/80 were excluded as non-relevant on the basis of: the abstract, title, study design, bias, and/or lack of relevance. Twelve articles were included in the qualitative analysis. Conclusions: Teleorthodontics can manage most emergencies, reassuring and following patients remotely. The aim set by dental teleassistance was met as it reduced patients’ office visits whilst maintaining regular monitoring, without compromising the results. Although our preliminary findings should be further investigated to objectively evaluate the efficacy, cost-effectiveness, and long-term results, we are confident that teleassistance in orthodontics will have a role to play in the near future. Full article
(This article belongs to the Collection Impact of COVID-19 on the Dental Community)
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Review
COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge
J. Clin. Med. 2020, 9(6), 1753; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061753 - 05 Jun 2020
Cited by 123
Abstract
Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the [...] Read more.
Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group—from infants to the elderly—resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity—from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients. Full article
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Review
Photobiomodulation—Underlying Mechanism and Clinical Applications
J. Clin. Med. 2020, 9(6), 1724; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061724 - 03 Jun 2020
Cited by 57
Abstract
The purpose of this study is to explore the possibilities for the application of laser therapy in medicine and dentistry by analyzing lasers’ underlying mechanism of action on different cells, with a special focus on stem cells and mechanisms of repair. The interest [...] Read more.
The purpose of this study is to explore the possibilities for the application of laser therapy in medicine and dentistry by analyzing lasers’ underlying mechanism of action on different cells, with a special focus on stem cells and mechanisms of repair. The interest in the application of laser therapy in medicine and dentistry has remarkably increased in the last decade. There are different types of lasers available and their usage is well defined by different parameters, such as: wavelength, energy density, power output, and duration of radiation. Laser irradiation can induce a photobiomodulatory (PBM) effect on cells and tissues, contributing to a directed modulation of cell behaviors, enhancing the processes of tissue repair. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), can induce cell proliferation and enhance stem cell differentiation. Laser therapy is a non-invasive method that contributes to pain relief and reduces inflammation, parallel to the enhanced healing and tissue repair processes. The application of these properties was employed and observed in the treatment of various diseases and conditions, such as diabetes, brain injury, spinal cord damage, dermatological conditions, oral irritation, and in different areas of dentistry. Full article
(This article belongs to the Section Clinical Cytology)
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Review
Acute Coronary Syndromes and Covid-19: Exploring the Uncertainties
J. Clin. Med. 2020, 9(6), 1683; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061683 - 02 Jun 2020
Cited by 42
Abstract
Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. [...] Read more.
Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. The initial data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss the pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; and learnings that have emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection. Full article
(This article belongs to the Section Cardiology)
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Review
COVID-19 Related Coagulopathy: A Distinct Entity?
J. Clin. Med. 2020, 9(6), 1651; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061651 - 31 May 2020
Cited by 59
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
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Review
Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials
J. Clin. Med. 2020, 9(5), 1583; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051583 - 23 May 2020
Cited by 70
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized [...] Read more.
Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19. Full article
(This article belongs to the Section Infectious Diseases)
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