Special Issue "SARS-CoV-2 Infection and COVID-19 Disease"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Luis Martinez-Sobrido
E-Mail Website
Guest Editor
1. Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14625, USA
2. Texas Biomedical Research Institute, San Antonio, TX 78245, USA
Interests: virology; vaccines; antivirals; influenza viruses; arenaviruses; Zika virus; coronavirus; SARS-CoV-2; COVID-19; innate immunity; adaptive immunity; interferon; virus-host interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Marta L. DeDiego
E-Mail Website
Guest Editor
Department of Molecular and Cellular Biology, National Center for Biotechnology-Spanish National Research Council, Madrid 28049, Spain
Interests: virology; influenza; coronavirus; innate immunity; virus-host interactions; interferons; inflammation; vaccines; antivirals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In December 2019, a previously unknown coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. SARS-CoV-2 is the causative agent of coronavirus disease 2019 (COVID-19), a world-wide pandemic that has dramatically impacted the global human public health and socioeconomic activities across the world with a magnitude not seen since the “Spanish flu” pandemic in 1918/1919.

Global efforts to develop a vaccine have resulted in several promising COVID-19 vaccine candidates with excellent safety and efficacy profiles. Currently, three vaccines have been approved by the Food and Drug Administration (FDA) for emergency use for the treatment of SARS-CoV-2 infection.

The goal of this Special Issue “SARS-CoV-2 Infection and COVID-19 Disease” is to cover aspects related to viral infection and pathogenesis, epidemiology and evolution, virus–host interactions, prophylactic vaccine development, therapeutic antivirals, neutralizing antibodies, innate and adaptive immune responses, reverse genetics approaches, recombinant viruses, reporter-expressing viruses, animal models of viral infection, pathogenesis and transmission, and COVID-19 disease.

We hope this Special Issue will provide researchers with new insights on the biology of SARS-CoV-2 infection and its associated COVID-19 disease with the goal of unifying efforts to develop effective countermeasures to protect against SARS-CoV-2 infection and COVID-19 disease.

Prof. Dr. Luis Martinez-Sobrido
Dr. Marta L. DeDiego
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • COVID-19
  • viral infection
  • viral pathogenesis
  • viral transmission
  • epidemiology and evolution
  • virus-host interactions
  • prophylactics
  • vaccines
  • therapeutics
  • antivirals
  • neutralizing antibodies
  • innate immunity
  • adaptive immunity
  • reverse genetics systems
  • animal models

Published Papers (9 papers)

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Research

Article
In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2
Pathogens 2021, 10(11), 1362; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111362 - 21 Oct 2021
Viewed by 233
Abstract
The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the “gold standard” of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the [...] Read more.
The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the “gold standard” of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Competing Bioaerosols May Influence the Seasonality of Influenza-Like Illnesses, including COVID-19. The Chicago Experience
Pathogens 2021, 10(9), 1204; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091204 - 16 Sep 2021
Cited by 2 | Viewed by 834
Abstract
Data from Chicago confirm the end of flu season coincides with the beginning of pollen season. More importantly, the end of flu season also coincides with onset of seasonal aerosolization of mold spores. Overall, the data suggest bioaerosols, especially mold spores, compete with [...] Read more.
Data from Chicago confirm the end of flu season coincides with the beginning of pollen season. More importantly, the end of flu season also coincides with onset of seasonal aerosolization of mold spores. Overall, the data suggest bioaerosols, especially mold spores, compete with viruses for a shared receptor, with the periodicity of influenza-like illnesses, including COVID-19, a consequence of seasonal factors that influence aerosolization of competing species. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection
Pathogens 2021, 10(9), 1197; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091197 - 15 Sep 2021
Viewed by 804
Abstract
Previously, we reported that immunomodulatory lactobacilli, nasally administered, beneficially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory [...] Read more.
Previously, we reported that immunomodulatory lactobacilli, nasally administered, beneficially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory effects of viable and non-viable Lactiplantibacillus plantarum strains in human respiratory epithelial cells (Calu-3 cells) and the capacity of these immunobiotic lactobacilli to reduce their susceptibility to the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immunobiotic L. plantarum MPL16 and CRL1506 differentially modulated IFN-β, IL-6, CXCL8, CCL5 and CXCL10 production and IFNAR2, DDX58, Mx1 and OAS1 expression in Calu-3 cells stimulated with the TLR3 agonist poly(I:C). Furthermore, the MPL16 and CRL1506 strains increased the resistance of Calu-3 cells to the challenge with SARS-CoV-2. L. plantarum MPL16 induced these beneficial effects more efficiently than the CRL1506 strain. Of note, neither non-viable MPL16 and CRL1506 strains nor the non-immunomodulatory strains L. plantarum CRL1905 and MPL18 could modify the resistance of Calu-3 cells to SARS-CoV-2 infection or the immune response to poly(I:C) challenge. To date, the potential beneficial effects of immunomodulatory probiotics on SARS-CoV-2 infection and COVID-19 outcome have been extrapolated from studies carried out in the context of other viral pathogens. To the best of our knowledge, this is the first demonstration of the ability of immunomodulatory lactobacilli to positively influence the replication of the new coronavirus. Further mechanistic studies and in vivo experiments in animal models of SARS-CoV-2 infection are necessary to identify specific strains of beneficial immunobiotic lactobacilli like L. plantarum MPL16 or CRL1506 for the prevention or treatment of the COVID-19. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Indian Herb-Derived Phytoconstituent-Based Antiviral, Antimicrobial and Antifungal Formulation: An Oral Rinse Candidate for Oral Hygiene and the Potential Prevention of COVID-19 Outbreaks
Pathogens 2021, 10(9), 1130; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091130 - 02 Sep 2021
Viewed by 742
Abstract
Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different [...] Read more.
Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different lines of treatment, such as vaccines and antiviral drugs. To find the appropriate prevention/treatment, 21 plant-based ingredients (Glycyrrhizin, Withanone, Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Kaempferol, Progallin A, Gallic acid, Naringin, Quercetin, Luteolin, and Apigenin) having antiviral, antibacterial and antifungal properties were identified. We pseudo-typed SARS-CoV-2 on a lentiviral vector plasmid and tested the impact of five different herbal formulations in mammalian HEK293T cells. Viral inactivation assay showed that the natural extracts in a herb-derived phytoconstituent-based formulation, BITS-003, comprising Bacopa monnieri, Glycyerrhiza glabra, Asparagus racemosus-wild, and Nigella sativa had strong virucidal properties, inactivating enveloped viruses from 2log10 (or 99%) to >4log10 (or 99.99%). Moreover, bacterial and yeast cells treated with BITS-003 displayed reduced growth. Topical use of the formulation as a mouthwash/gargle could be effective in reducing symptoms of respiratory viral infections, with the potential to decrease the viral load in the buccal/oral cavity. This may inhibit the coronavirus spreading to the lungs of infected persons and at the same time may reduce the risk of viral transmission to other susceptible persons through micro-droplets originating from the oral cavity of the infected person. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Clinico-Genomic Analysis Reveals Mutations Associated with COVID-19 Disease Severity: Possible Modulation by RNA Structure
Pathogens 2021, 10(9), 1109; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091109 - 31 Aug 2021
Viewed by 804
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests a broad spectrum of clinical presentations, varying in severity from asymptomatic to mortality. As the viral infection spread, it evolved and developed into many variants of concern. Understanding the impact of mutations in the SARS-CoV-2 [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests a broad spectrum of clinical presentations, varying in severity from asymptomatic to mortality. As the viral infection spread, it evolved and developed into many variants of concern. Understanding the impact of mutations in the SARS-CoV-2 genome on the clinical phenotype and associated co-morbidities is important for treatment and preventionas the pandemic progresses. Based on the mild, moderate, and severe clinical phenotypes, we analyzed the possible association between both, the clinical sub-phenotypes and genomic mutations with respect to the severity and outcome of the patients. We found a significant association between the requirement of respiratory support and co-morbidities. We also identified six SARS-CoV-2 genome mutations that were significantly correlated with severity and mortality in our cohort. We examined structural alterations at the RNA and protein levels as a result of three of these mutations: A26194T, T28854T, and C25611A, present in the Orf3a and N protein. The RNA secondary structure change due to the above mutations can be one of the modulators of the disease outcome. Our findings highlight the importance of integrative analysis in which clinical and genetic components of the disease are co-analyzed. In combination with genomic surveillance, the clinical outcome-associated mutations could help identify individuals for priority medical support. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Acute Inflammatory Mediators in Young Adult Patients with COVID-19 in Mexico
Pathogens 2021, 10(8), 1056; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10081056 - 20 Aug 2021
Viewed by 1309
Abstract
Young adults (18–40 years old) are an active population with high risk of infection and transmission of COVID-19. They are considered a low-risk population due to its low 1.0% case fatality rate (CFR). Despite their high clinical usefulness to prevent fatal cases, inflammatory [...] Read more.
Young adults (18–40 years old) are an active population with high risk of infection and transmission of COVID-19. They are considered a low-risk population due to its low 1.0% case fatality rate (CFR). Despite their high clinical usefulness to prevent fatal cases, inflammatory and coagulation biomarkers studies are limited. For this reason, we performed a retrospective cohort study with COVID-19 patients in Hermosillo, Mexico, to assess inflammation, coagulopathy profile, and severity outcomes in young adults. We analyzed blood samples to determine the neutrophil/lymphocyte ratio (NLR), neutrophil/monocyte ratio (NMR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), and C-reactive protein (C-RP). We included epidemiological features and comorbidities, and compared them to the severity status. Only 359 COVID-19-confirmed young adults were included in the ambulatory (44.8%), hospitalized (42.9%), and death (12%) severity groups. Laboratory results showed an increase in NMR, LMR, and C-RP associated with the aggravated patients. Additionally, obesity, arterial hypertension, and type-2 diabetes mellitus (T2DM) were associated with the COVID-19 severity outcome. We found that 9.1% and 30.3% of young adults presented the novel COVID-19-associated coagulopathy (CAC) and the risk of CAC, respectively. These parameters can be considered independent biomarkers reflecting an enhanced inflammatory process related to the COVID-19 prognosis. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
SARS-CoV-2 Seroprevalence and Neutralizing Antibody Response after the First and Second COVID-19 Pandemic Wave in Croatia
Pathogens 2021, 10(6), 774; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060774 - 20 Jun 2021
Cited by 3 | Viewed by 1028
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with a pandemic spread. So far, a total of 349,910 SARS-CoV-2 cases and 7687 deaths were reported in Croatia. We analyzed the seroprevalence and neutralizing (NT) antibody response in the Croatian general [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with a pandemic spread. So far, a total of 349,910 SARS-CoV-2 cases and 7687 deaths were reported in Croatia. We analyzed the seroprevalence and neutralizing (NT) antibody response in the Croatian general population after the first (May–July 2020) and second (December 2020–February 2021) pandemic wave. Initial serological testing was performed using a commercial ELISA, with confirmation of reactive samples by a virus neutralization test (VNT). A significant difference in the overall seroprevalence rate was found after the first (ELISA 2.2%, VNT 0.2%) and second waves (ELISA 25.1%, VNT 18.7%). Seropositive individuals were detected in all age groups, with significant differences according to age. The lowest prevalence of NT antibodies was documented in the youngest (<10 years; 16.1%) and the oldest (60–69/70+ years; 16.0% and 12.8%, respectively) age groups. However, these age groups showed the highest median NT titers (32–64). In other groups, seropositivity varied from 19.3% to 21.5%. A significant weak positive correlation between binding antibody level as detected by ELISA and VNT titer (rho = 0.439, p < 0.001) was observed. SARS-CoV-2 NT antibody titers seem to be age-related, with the highest NT activity in children under 10 years and individuals above 50 years. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Communication
Dolosigranulum pigrum Modulates Immunity against SARS-CoV-2 in Respiratory Epithelial Cells
Pathogens 2021, 10(6), 634; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060634 - 21 May 2021
Cited by 2 | Viewed by 1356
Abstract
In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed [...] Read more.
In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to increase the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice
Pathogens 2021, 10(5), 626; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050626 - 19 May 2021
Cited by 1 | Viewed by 1622
Abstract
The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there [...] Read more.
The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response. Full article
(This article belongs to the Special Issue SARS-CoV-2 Infection and COVID-19 Disease)
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