Coronavirus Disease (COVID-19): Pathophysiology, Epidemiology and Clinical Management

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 18105

Special Issue Editor


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Guest Editor
UPMC Montefiore, NW628, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
Interests: COVID-19; murine coronavirus; SARS-CoV-2; MHV; post coronaviral bacterial infections; type I interferons; type II interferons; lung injury
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Special Issue Information

Dear Colleagues,

As the COVID-19 pandemic continues to cause a large number of infections and inflict significant morbidity and mortality, despite the widespread use of vaccination, it is imperative to understand specific pathological mechanisms that contribute to the disease and its clinical outcomes. In this Special Issue, we aim to publish manuscripts that cover three important aspects of COVID-19 biology:

Epidemiology: The unique aspects of COVID-19 epidemiology that determine the transmission of the virus. These aspects may include viral load and symptom kinetics, novel aspects of mask use, effect of vaccination and antiviral therapy and other aspects that control the viral transmission.

Pathophysiology: Since its emergence, significant advances in understanding COVID-19 pathophysiology have been made. We hope to publish the knowledge on the novel aspects of COVID-19 pathology, both in the lungs (acute lung injury and ARDS) and systemically (cytokine storm, coagulation and multi-organ failure), which both determine clinical outcomes.

Clinical Management: The therapeutic management of COVID-19 has improved significantly in the last 2 years. We aim to publish novel research/insightful reviews on the therapeutic aspects of COVID-19, including but not limited to the topics of antivirals, host protection, and symptomatic management.

Dr. Lokesh Kumar Sharma
Guest Editor

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Keywords

  • COVID-19
  • SARS-CoV-2
  • viral transmission
  • lung injury
  • coronavirus-pathology
  • cytokine storm

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Published Papers (8 papers)

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Research

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15 pages, 1149 KiB  
Article
Reduction in SARS-CoV-2 Virus Infectivity in Human and Hamster Feces
by Sébastien Wurtzer, Sandra Lacote, Severine Murri, Philippe Marianneau, Elodie Monchatre-Leroy, Mickaël Boni, Olivier Ferraris, Yvon Maday, Ousmane Kébé, Ndongo Dia, Christophe Peyrefitte, Harry Sokol, OBEPINE Consortium, Laurent Moulin and Vincent Maréchal
Viruses 2022, 14(8), 1777; https://doi.org/10.3390/v14081777 - 15 Aug 2022
Cited by 5 | Viewed by 2270
Abstract
Objective: There is extensive evidence that SARS-CoV-2 replicates in the gastrointestinal tract. However, the infectivity of virions in feces is poorly documented. Although the primary mode of transmission is airborne, the risk of transmission from contaminated feces remains to be assessed. Design: The [...] Read more.
Objective: There is extensive evidence that SARS-CoV-2 replicates in the gastrointestinal tract. However, the infectivity of virions in feces is poorly documented. Although the primary mode of transmission is airborne, the risk of transmission from contaminated feces remains to be assessed. Design: The persistence of SARS-CoV-2 (infectivity and RNA) in human and animal feces was evaluated by virus isolation on cell culture and RT-qPCR, respectively. The exposure of golden Syrian hamsters to experimentally contaminated feces through intranasal inoculation has also been tested to assess the fecal-oral transmission route. Results: For periods that are compatible with average intestinal transit, the SARS-CoV-2 genome was noticeably stable in human and animal feces, contrary to the virus infectivity that was reduced in a time- and temperature-dependent manner. In human stools, this reduction was variable depending on the donors. Viral RNA was excreted in the feces of infected hamsters, but exposure of naïve hamsters to feces of infected animals did not lead to any productive infection. Conversely, hamsters could be experimentally infected following exposure to spiked fresh feces. Conclusion: Infection following exposure to naturally contaminated feces has been suspected but has not been established so far. The present work demonstrates that SARS-CoV-2 rapidly lost infectivity in spiked or naturally infected feces. Although the possibility of persistent viral particles in human or animal feces cannot be fully ruled out, SARS-CoV-2 transmission after exposure to contaminated feces is unlikely. Full article
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10 pages, 901 KiB  
Article
Clinical Aspects of the Subsequent SARS-CoV-2 Waves in Children from 2020 to 2022—Data from a Local Cohort in Cologne, Germany (n = 21,635)
by Meike Meyer, Esra Ruebsteck, Felix Dewald, Florian Klein, Clara Lehmann, Christoph Huenseler and Lutz Thorsten Weber
Viruses 2022, 14(8), 1607; https://doi.org/10.3390/v14081607 - 23 Jul 2022
Cited by 5 | Viewed by 1409
Abstract
Almost two and a half years after the appearance of the first cases of SARS-CoV-2 in December 2019, more than 500 million people have been infected with SARS-CoV-2 and over 6 million have died of it worldwide. In terms of the pediatric cohort, [...] Read more.
Almost two and a half years after the appearance of the first cases of SARS-CoV-2 in December 2019, more than 500 million people have been infected with SARS-CoV-2 and over 6 million have died of it worldwide. In terms of the pediatric cohort, it already became evident at an early stage that the infection causes milder symptoms in children and rarely runs a fatal course. Objective: This work presents data gathered over a period of over two years in patients between the age of 0 and 18 years. The aim is to provide information on the clinical aspects of the five different SARS-CoV-2 waves. Methods: Between 13 March 2020 and 22 April 2022, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 at our clinic were included. Data were collected on standardized questionnaires. The analysis of the data was anonymized and retrospective. Results: We investigated 21,635 NAATs, of which 1028 of the tests were positive (4.8%). The highest rate of positive results was observed in the fifth wave (541/2.292 NAATs (23.6%)). Most of the children who were hospitalized were hospitalized in wave three (22.9%). The availability of a vaccine was followed by a decrease in positive NAATs in the corresponding age group thereafter. Conclusions: These data underline the fact that children infected with SARS-CoV-2, regardless of which VOC, are often only mildly affected. Vaccinations seem to remain the key to avoid massive numbers of infected people and a potential collapse of the healthcare systems. Full article
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9 pages, 1187 KiB  
Article
The Divergent Pattern of SARS-CoV-2 Variant Predominance and Transmission Dynamics in the Brazilian Island of Ilhabela
by Vincent Louis Viala, Svetoslav Nanev Slavov, Loyze Paola Oliveira de Lima, Alex Ranieri Jeronimo Lima, Gabriela Ribeiro, Antonio Jorge Martins, Bruna Petry, Cecilia Artico Banho, Claudia Renata dos Santos Barros, Cristina Tschorny Moncau, Debora Botequio Moretti, Debora Glenda Lima de La-Roque, Elaine Cristina Marqueze, Elisangela Chicaroni Mattos, Felipe Allan da Silva da Costa, Heidge Fukumasu, Jardelina de Souza Todao Bernardino, Jayme A. Souza-Neto, Jessika Cristina Chagas Lesbon, Lara Passos Kayanoki, Leandro Lombo Bernardo, Lívia Sacchetto, Luan Gaspar Clemente, Luiz Carlos Júnior Alcantara, Luiz Lehmann Coutinho, Beatriz de Carvalho Marques, Marta Giovanetti, Maurício Lacerda Nogueira, Mirele Daiana Poleti, Patricia Akemi Assato, Pedro De Queiroz Cattony Neto, Raquel de Lello Rocha Campos Cassano, Raul Machado Neto, Rejane Maria Tommasini Grotto, Ricardo Augusto Brassaloti, Simone Kashima, Dimas Tadeu Covas, Maria Carolina Elias and Sandra Coccuzzo Sampaioadd Show full author list remove Hide full author list
Viruses 2022, 14(7), 1481; https://doi.org/10.3390/v14071481 - 5 Jul 2022
Cited by 3 | Viewed by 2107
Abstract
Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised [...] Read more.
Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised concerns for closer surveillance on this island. Therefore, we intensified the surveillance for 24 weeks by generating data from 34% of local positive cases. Our data show that the patterns of VOC predominance dynamics and infection rates were in general distinct from the mainland. We report here the first known case of Alpha predominance in a Brazilian population, a delay greater than 3 months for the Gamma to dominate the previous variants compared to the mainland, and a faster dispersion rate of Gamma and Delta VOCs compared to the mainland. Phylogenetic analysis revealed the SARS-CoV-2 transmission dynamics in Ilhabela were characterized by multiple independent introduction events of Gamma and Delta, with a few events of Alpha introduction, two of them followed by community transmission. This study evidenced the peculiar behavior of SARS-CoV-2 variants in an isolated population and brought to light the importance of specific programs for SARS-CoV-2 genomic surveillance in isolated populations. Full article
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11 pages, 1612 KiB  
Article
Effect of Casirivimab/Imdevimab Treatment on Serum Type I Interferon Levels in SARS-CoV-2 Infection
by Kentaro Nagaoka, Hitoshi Kawasuji, Yusuke Takegoshi, Yushi Murai, Makito Kaneda, Akitoshi Ueno, Yuki Miyajima, Hideki Niimi, Yoshitomo Morinaga and Yoshihiro Yamamoto
Viruses 2022, 14(7), 1399; https://doi.org/10.3390/v14071399 - 27 Jun 2022
Cited by 4 | Viewed by 2245
Abstract
The effects of casirivimab and imdevimab (C/I) on the innate immune response against SARS-CoV-2 infection remain unclear. We evaluated the effect of C/I on type I interferon (IFN-I) and cytokines in patients with SARS-CoV-2 infection. This prospective observational study recruited consecutive patients hospitalized [...] Read more.
The effects of casirivimab and imdevimab (C/I) on the innate immune response against SARS-CoV-2 infection remain unclear. We evaluated the effect of C/I on type I interferon (IFN-I) and cytokines in patients with SARS-CoV-2 infection. This prospective observational study recruited consecutive patients hospitalized with SARS-CoV-2 infection. Blood levels of IFN-I and cytokines before and after C/I administration were assessed using enzyme-linked immunoassay. The study enrolled 29 patients in the C/I group. In addition, 11 patients who received remdesivir and dexamethasone (R/D group) during the early phase (≤5 days after the onset of symptoms) were included as a comparator group. After treatment, IFN-α and IFN-β levels decreased significantly in both the C/I group and R/D group, whilst the post-treatment neutrophil-to-lymphoid ratio increased in the early C/I group but not the R/D group. In the C/I group, temporal temperature elevation and hypoxemia were observed after treatment in 58.6% and 41.4% of the cohort, respectively. However, most patients recovered by 5 days after treatment. This study could demonstrate the high therapeutic effect of C/I with an antibody-dependent enhancement-like response and decreased IFN-I production, which was likely due to the immediate induction of an antibody-dependent immune response against SARS-CoV-2. Full article
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11 pages, 1122 KiB  
Article
Mortality in SARS-CoV-2 Hospitalized Patients Treated with Remdesivir: A Nationwide, Registry-Based Study in Italy
by Pierluigi Russo, Evelina Tacconelli, Pier Paolo Olimpieri, Simone Celant, Antonietta Colatrella, Luca Tomassini and Giorgio Palù
Viruses 2022, 14(6), 1197; https://doi.org/10.3390/v14061197 - 31 May 2022
Cited by 9 | Viewed by 1913
Abstract
Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated [...] Read more.
Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated with remdesivir to assess the impact of major confounders on crude 15-day and 29-day mortality. Mortality was calculated using the Kaplan–Meier estimator and the Cox proportional-hazards model was applied to analyze the risks by patient’s baseline features. In total, 16,462 patients treated with remdesivir from 29 October 2020 to 17 December 2020 were entered in the study. Crude 15-day and 29-day mortality were 7.1% (95% CI, 6.7–7.5%) and 11.7% (95% CI, 11.2–12.2%), respectively. Being treated within two days of admission reduced the risk of death by about 40% (HR 1.4, 95% CI, 1.2–1.6). Results from the largest cohort of remdesivir-treated patients suggests that mortality in SARS-CoV-2 hospitalized patients is substantially influenced by the days between SARS-CoV-2 diagnosis and drug prescription. Current recommendations and future clinical trials for remdesivir alone or in combination should carefully consider the target population and timing for best efficacy of treatment. Full article
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8 pages, 732 KiB  
Article
Can Individuals with Suboptimal Antibody Responses to Conventional Antiviral Vaccines Acquire Adequate Antibodies from SARS-CoV-2 mRNA Vaccination?
by Wataru Ogura, Kouki Ohtsuka, Sachiko Matsuura, Takahiro Okuyama, Satsuki Matsushima, Satoko Yamasaki, Hiroyuki Miyagi, Kumiko Sekiguchi, Hiroaki Ohnishi and Takashi Watanabe
Viruses 2022, 14(5), 956; https://doi.org/10.3390/v14050956 - 3 May 2022
Viewed by 1744
Abstract
In Japan, healthcare workers (HCWs) are vaccinated against measles, rubella, chickenpox, mumps, and hepatitis B to prevent nosocomial infection; however, some do not produce sufficient antibodies (“suboptimal responders”). This study compared immune responses to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) [...] Read more.
In Japan, healthcare workers (HCWs) are vaccinated against measles, rubella, chickenpox, mumps, and hepatitis B to prevent nosocomial infection; however, some do not produce sufficient antibodies (“suboptimal responders”). This study compared immune responses to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine among HCWs with normal and suboptimal responses to conventional vaccines. In this prospective cohort study, 50 HCWs received two doses of BNT162b2 mRNA vaccine 3 weeks apart. SARS-CoV-2 anti-spike antibodies were measured 11 times, starting before the first vaccination and ending 5 months after the second vaccination. Antibody titers of four suboptimal and 46 normal responders were compared. SARS-CoV-2 neutralizing antibody activity was measured twice in suboptimal responders, 1 week/1 month and 5 months after the second vaccination. The SARS-CoV-2 anti-spike antibody was detectable in the samples from suboptimal and normal responders at each timepoint after vaccination. Suboptimal responders exhibited SARS-CoV-2 neutralizing antibody activity 1 week/1 month as well as 5 months after the second vaccination; however, activity was slightly reduced at 5 months. Our findings show that suboptimal responders do acquire adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies from vaccination to prevent SARS-CoV-2. SARS-CoV-2 mRNA vaccines should thus be recommended for both normal and suboptimal responders to conventional vaccines. Full article
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14 pages, 908 KiB  
Article
Simplified Acute Physiology Score 3 Performance in Austrian COVID-19 Patients Admitted to Intensive Care Units with and without Diabetes
by Faisal Aziz, Alexander Christian Reisinger, Felix Aberer, Caren Sourij, Norbert Tripolt, Jolanta M. Siller-Matula, Dirk von-Lewinski, Philipp Eller, Susanne Kaser, Harald Sourij and on behalf of the COVID-19 in Diabetes in Austria Study Group
Viruses 2022, 14(4), 777; https://doi.org/10.3390/v14040777 - 8 Apr 2022
Cited by 6 | Viewed by 2187
Abstract
This study evaluated and compared the performance of simplified acute physiology score 3 (SAPS 3) for predicting in-hospital mortality in COVID-19 patients admitted to intensive care units (ICUs) with and without diabetes in Austria. The Austrian national public health institute (GÖG) data of [...] Read more.
This study evaluated and compared the performance of simplified acute physiology score 3 (SAPS 3) for predicting in-hospital mortality in COVID-19 patients admitted to intensive care units (ICUs) with and without diabetes in Austria. The Austrian national public health institute (GÖG) data of COVID-19 patients admitted to ICUs (n = 5850) were analyzed. Three versions of SAPS 3 were used: standard equation, Central European equation, and Austrian equation customized for COVID-19 patients. The observed in-hospital mortality was 38.9%, 42.9%, and 37.3% in all, diabetes, and non-diabetes patients, respectively. The overall C-statistics was 0.69 with an insignificant (p = 0.193) difference between diabetes (0.70) and non-diabetes (0.68) patients. The Brier score was > 0.20 for all SAPS 3 equations in all cohorts. Calibration was unsatisfactory for both standard and Central European equations in all cohorts, whereas it was satisfactory for the Austrian equation in diabetes patients only. The SAPS 3 score demonstrated low discrimination and accuracy in Austrian COVID-19 patients, with an insignificant difference between diabetes and non-diabetes. All equations were miscalibrated particularly in non-diabetes patients, while the Austrian equation showed satisfactory calibration in diabetes patients only. Both uncalibrated and calibrated versions of SAPS 3 should be used with caution in COVID-19 patients. Full article
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Review

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15 pages, 962 KiB  
Review
An Update on the Mutual Impact between SARS-CoV-2 Infection and Gut Microbiota
by Shaoshuai Li, Yang Zhou, Dongmei Yan and Yanmin Wan
Viruses 2022, 14(8), 1774; https://doi.org/10.3390/v14081774 - 15 Aug 2022
Cited by 9 | Viewed by 2804
Abstract
The gut microbiota is essential for good health. It has also been demonstrated that the gut microbiota can regulate immune responses against respiratory tract infections. Since the outbreak of the COVID-19 pandemic, accumulating evidence suggests that there is a link between the severity [...] Read more.
The gut microbiota is essential for good health. It has also been demonstrated that the gut microbiota can regulate immune responses against respiratory tract infections. Since the outbreak of the COVID-19 pandemic, accumulating evidence suggests that there is a link between the severity of COVID-19 and the alteration of one’s gut microbiota. The composition of gut microbiota can be profoundly affected by COVID-19 and vice versa. Here, we summarize the observations of the mutual impact between SARS-CoV-2 infection and gut microbiota composition. We discuss the consequences and mechanisms of the bi-directional interaction. Moreover, we also discuss the immune cross-reactivity between SARS-CoV-2 and commensal bacteria, which represents a previously overlooked connection between COVID-19 and commensal gut bacteria. Finally, we summarize the progress in managing COVID-19 by utilizing microbial interventions. Full article
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