SARS-CoV-2 Infection and COVID-19 Disease (Closed)

A topical collection in Pathogens (ISSN 2076-0817). This collection belongs to the section "Immunological Responses and Immune Defense Mechanisms".

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Editors


E-Mail Website
Collection 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

E-Mail Website
Collection 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

Topical Collection 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 Topical Collection “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 Topical Collection 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
Collection Editors

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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 (22 papers)

2024

Jump to: 2023, 2022, 2021

7 pages, 184 KiB  
Editorial
Editorial for the Topical Collection “SARS-CoV-2 Infection and COVID-19 Disease”
by Luis Martinez-Sobrido and Marta L. DeDiego
Pathogens 2024, 13(3), 191; https://doi.org/10.3390/pathogens13030191 - 21 Feb 2024
Viewed by 1339
Abstract
A previously unknown coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in the city of Wuhan, China, in December 2019 [...] Full article

2023

Jump to: 2024, 2022, 2021

16 pages, 2154 KiB  
Review
The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic
by Linda Petrone, Alessandro Sette, Rory D. de Vries and Delia Goletti
Pathogens 2023, 12(7), 862; https://doi.org/10.3390/pathogens12070862 - 22 Jun 2023
Cited by 16 | Viewed by 2297
Abstract
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell [...] Read more.
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to “classical” T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial. Full article
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33 pages, 2569 KiB  
Review
The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups
by Zainalabideen A. Abdulla, Sharaf M. Al-Bashir, Hiba Alzoubi, Noor S. Al-Salih, Ala A. Aldamen and Ahmed Z. Abdulazeez
Pathogens 2023, 12(2), 329; https://doi.org/10.3390/pathogens12020329 - 15 Feb 2023
Cited by 4 | Viewed by 5571
Abstract
This study aims to review the available data regarding the central role of immunity in combating SARS-CoV-2 infection and in the generation of protection by vaccination against COVID-19 in different age groups. Physiologically, the immune response and the components involved in it are [...] Read more.
This study aims to review the available data regarding the central role of immunity in combating SARS-CoV-2 infection and in the generation of protection by vaccination against COVID-19 in different age groups. Physiologically, the immune response and the components involved in it are variable, both functionally and quantitatively, in neonates, infants, children, adolescents, and adults. These immunological differences are mirrored during COVID-19 infection and in the post-vaccination period. The outcome of SARS-CoV-2 infection is greatly dependent on the reaction orchestrated by the immune system. This is clearly obvious in relation to the clinical status of COVID-19 infection, which can be symptomless, mild, moderate, or severe. Even the complications of the disease show a proportional pattern in relation to the immune response. On the contrary, the commonly used anti-COVID-19 vaccines generate protective humoral and cellular immunity. The magnitude of this immunity and the components involved in it are discussed in detail. Furthermore, many of the adverse effects of these vaccines can be explained on the basis of immune reactions against the different components of the vaccines. Regarding the appropriate choice of vaccine for different age groups, many factors have to be considered. This is a cornerstone, particularly in the following age groups: 1 day to 5 years, 6 to 11 years, and 12 to 17 years. Many factors are involved in deciding the route, doses, and schedule of vaccination for children. Another important issue in this dilemma is the hesitancy of families in making the decision about whether to vaccinate their children. Added to these difficulties is the choice by health authorities and governments concerning whether to make children’s vaccination compulsory. In this respect, although rare and limited, adverse effects of vaccines in children have been detected, some of which, unfortunately, have been serious or even fatal. However, to achieve comprehensive control over COVID-19 in communities, both children and adults have to be vaccinated, as the former group represents a reservoir for viral transmission. The understanding of the various immunological mechanisms involved in SARS-CoV-2 infection and in the preparation and application of its vaccines has given the sciences a great opportunity to further deepen and expand immunological knowledge. This will hopefully be reflected positively on other diseases through gaining an immunological background that may aid in diagnosis and therapy. Humanity is still in continuous conflict with SARS-CoV-2 infection and will be for a while, but the future is expected to be in favor of the prevention and control of this disease. Full article
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2022

Jump to: 2024, 2023, 2021

13 pages, 1140 KiB  
Article
Diagnosis of SARS-CoV-2 during the Pandemic by Multiplex RT-rPCR hCoV Test: Future Perspectives
by Alessio Danilo Inchingolo, Ciro Isacco Gargiulo, Giuseppina Malcangi, Anna Maria Ciocia, Assunta Patano, Daniela Azzollini, Fabio Piras, Giuseppe Barile, Vito Settanni, Antonio Mancini, Grazia Garofoli, Giulia Palmieri, Chiara Di Pede, Biagio Rapone, Angelo Michele Inchingolo, Megan Jones, Alberto Corriero, Nicola Brienza, Antonio Parisi, Angelica Bianco, Loredana Capozzi, Laura Del Sambro, Domenico Simone, Ioana Roxana Bordea, Gianluca Martino Tartaglia, Antonio Scarano, Felice Lorusso, Luigi Macchia, Giovanni Migliore, Van Hung Pham, Gianna Dipalma and Francesco Inchingoloadd Show full author list remove Hide full author list
Pathogens 2022, 11(11), 1378; https://doi.org/10.3390/pathogens11111378 - 18 Nov 2022
Cited by 11 | Viewed by 2350
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a significant threat to public health. However, among the Coronaviridae family members, there are other viruses that can also cause infections in humans. Among these, severe acute [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a significant threat to public health. However, among the Coronaviridae family members, there are other viruses that can also cause infections in humans. Among these, severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) have posed significant threats to human health in the past. Other human pathogenic coronaviruses have been identified, and they are known to cause respiratory diseases with manifestations ranging from mild to severe. In this study, we evaluated the performance of a multiplex RT-rPCR specific to seven human pathogenic coronaviruses in mainly detecting SARS-CoV-2 directly from nasopharyngeal swabs obtained from suspected COVID-19 infected patients, while simultaneously detecting different human pathogenic coronaviruses in case these were also present. We tested 1195 clinical samples suspected of COVID-19 infection. The assay identified that 69% of the samples tested positive for SARS-CoV-2 (1195), which was confirmed using another SARS-CoV-2 RT-PCR kit available in our laboratory. None of these clinical samples were positive for SARS-CoV, MERS-CoV or HCoV. This means that during the endemic phase of COVID-19, infection with other human pathogenic coronaviruses, even the common cold coronavirus (HCoV), is very uncommon. Our study also confirmed that the multiplex RT-rPCR is a sensitive assay for detecting SARS-CoV-2 regardless of differences among the variants. This multiplex RT-rPCR is also time- and cost-saving and very easy to apply in the diagnostic laboratory due to its simple procedure and its stability in storage after preparation. These features make the assay a valuable approach in screening procedures for the rapid detection of SARS-CoV-2 and other human pathogenic coronaviruses that could affect public health. Full article
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12 pages, 1516 KiB  
Article
Intranasal Immunization with Liposome-Displayed Receptor-Binding Domain Induces Mucosal Immunity and Protection against SARS-CoV-2
by Wei-Chiao Huang, Kevin Chiem, Luis Martinez-Sobrido and Jonathan F. Lovell
Pathogens 2022, 11(9), 1035; https://doi.org/10.3390/pathogens11091035 - 12 Sep 2022
Cited by 11 | Viewed by 3050
Abstract
The global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to efforts in developing effective vaccine approaches. Currently, approved coronavirus disease 2019 (COVID-19) vaccines are administered through an intramuscular (I.M.) route. Here, we show that the SARS-CoV-2 spike (S) [...] Read more.
The global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to efforts in developing effective vaccine approaches. Currently, approved coronavirus disease 2019 (COVID-19) vaccines are administered through an intramuscular (I.M.) route. Here, we show that the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD), when displayed on immunogenic liposomes, can be intranasally (I.N.) administered, resulting in the production of antigen-specific IgA and antigen-specific cellular responses in the lungs. Following I.N. immunization, antigen-presenting cells of the lungs took up liposomes displaying the RBD. K18 human ACE2-transgenic mice that were immunized I.M or I.N with sub-microgram doses of RBD liposomes and that were then challenged with SARS-CoV-2 had a reduced viral load in the early course of infection, with I.M. achieving complete viral clearance. Nevertheless, both vaccine administration routes led to full protection against lethal viral infection, demonstrating the potential for the further exploration and optimization of I.N immunization with liposome-displayed antigen vaccines. Full article
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7 pages, 229 KiB  
Review
Monoclonal Antibodies for Pre- and Postexposure Prophylaxis of COVID-19: Review of the Literature
by Serena Vita, Silvia Rosati, Tommaso Ascoli Bartoli, Alessia Beccacece, Alessandra D’Abramo, Andrea Mariano, Laura Scorzolini, Delia Goletti and Emanuele Nicastri
Pathogens 2022, 11(8), 882; https://doi.org/10.3390/pathogens11080882 - 5 Aug 2022
Cited by 13 | Viewed by 5658
Abstract
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful microorganisms, including viruses such as Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2). The US Food and Drug Administration (FDA) and the European Medical Agency (EMA) have already authorized monoclonal antibodies [...] Read more.
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful microorganisms, including viruses such as Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2). The US Food and Drug Administration (FDA) and the European Medical Agency (EMA) have already authorized monoclonal antibodies of anti-SARS-CoV-2 to treat mild to moderate CoronaVIrus Disease-2019 (COVID-19) in patients at risk of developing severe disease. More recently, monoclonal antibodies anti-SARS-CoV-2 have been authorized for primary and secondary prophylaxis in patients at high risk of severe disease for background comorbidity. Primary or pre-exposure prophylaxis prevents COVID-19 in unexposed people, whereas secondary or postexposure prophylaxis prevent COVID-19 in recently exposed people to individuals with laboratory-confirmed SARS-CoV-2. This review focuses briefly on therapeutic indications of currently available monoclonal antibodies for COVID-19 pre- and postexposure prophylaxis and on the efficacy of convalescent plasma. Full article
17 pages, 1606 KiB  
Article
GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2
by Rena A. Mizrahi, Wendy Y. Lin, Ashley Gras, Ariel R. Niedecken, Ellen K. Wagner, Sheila M. Keating, Nikita Ikon, Vishal A. Manickam, Michael A. Asensio, Jackson Leong, Angelica V. Medina-Cucurella, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Renee Leong, Yoong Wearn Lim, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Dirk Büscher, Jose Vicente Terencio, Clara Di Germanio, Steven M. Chamow, Charles Olson, Paula A. Pino, Jun-Gyu Park, Amberlee Hicks, Chengjin Ye, Andreu Garcia-Vilanova, Luis Martinez-Sobrido, Jordi B. Torrelles, David S. Johnson and Adam S. Adleradd Show full author list remove Hide full author list
Pathogens 2022, 11(7), 806; https://doi.org/10.3390/pathogens11070806 - 19 Jul 2022
Cited by 5 | Viewed by 4165
Abstract
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can [...] Read more.
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus. Full article
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22 pages, 2277 KiB  
Article
SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations
by Brenda Martínez-González, María Eugenia Soria, Lucía Vázquez-Sirvent, Cristina Ferrer-Orta, Rebeca Lobo-Vega, Pablo Mínguez, Lorena de la Fuente, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruíz, Marta Cortón, Rosario López-Rodríguez, Carlos García-Crespo, Pilar Somovilla, Antoni Durán-Pastor, Isabel Gallego, Ana Isabel de Ávila, Soledad Delgado, Federico Morán, Cecilio López-Galíndez, Jordi Gómez, Luis Enjuanes, Llanos Salar-Vidal, Mario Esteban-Muñoz, Jaime Esteban, Ricardo Fernández-Roblas, Ignacio Gadea, Carmen Ayuso, Javier Ruíz-Hornillos, Nuria Verdaguer, Esteban Domingo and Celia Peralesadd Show full author list remove Hide full author list
Pathogens 2022, 11(6), 662; https://doi.org/10.3390/pathogens11060662 - 8 Jun 2022
Cited by 16 | Viewed by 4047
Abstract
Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented [...] Read more.
Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed. Full article
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12 pages, 1014 KiB  
Article
Anti-RBD IgA and IgG Response and Transmission in Breast Milk of Anti-SARS-CoV-2 Vaccinated Mothers
by Felicia Trofin, Eduard Vasile Nastase, Luminita Smaranda Iancu, Daniela Constantinescu, Corina Maria Cianga, Catalina Lunca, Ramona Gabriela Ursu, Petru Cianga and Olivia Simona Dorneanu
Pathogens 2022, 11(3), 286; https://doi.org/10.3390/pathogens11030286 - 24 Feb 2022
Cited by 17 | Viewed by 4440
Abstract
The appearance of the severe acute respiratory syndrome virus-2 (SARS-CoV-2) has had a significant impact on the balance of public health and social life. The data available so far show that newborns and young children do not develop severe forms of COVID-19, but [...] Read more.
The appearance of the severe acute respiratory syndrome virus-2 (SARS-CoV-2) has had a significant impact on the balance of public health and social life. The data available so far show that newborns and young children do not develop severe forms of COVID-19, but a small proportion of them will still need hospitalization. Even though young children represent an important vector of the infection, vaccination at such a young age was not yet considered. Thus, the question of whether potentially protective antibodies against SARS-CoV-2 could be provided to them via breast milk or across the placenta, as “passive immunity”, still stands. Materials and Methods: Between January–July 2021, we have conducted a prospective study that aimed to measure the immunoglobulin (Ig) A and IgG anti-SARS-CoV-2 titers in the breast milk of 28 vaccinated lactating mothers, sampled at 30 and 60 days after the second dose of the anti-SARS-CoV-2 Pfizer or Moderna mRNA vaccines. Anti-RBD reactive IgA and IgG antibodies were detected and quantified by a sandwich enzyme-linked immunosorbent assay. Results: Anti-RBD IgA and IgG were present in all breast milk samples, both in the first and in the second specimens, without a significant difference between those two. The anti-RBD IgA titers were approximately five-times higher than the anti-RBD IgG ones. The anti-RBD IgA and IgG titers were correlated with the infants’ age, but they were not correlated with the vaccine type or mother’s age. The anti-RBD IgA excreted in milk were inversely correlated with the parity number. Conclusions: Anti-SARS-CoV-2 IgA and IgG can be found in the milk secretion of mothers vaccinated with mRNA vaccines and, presumably, these antibodies should offer protection to the newborn, considering that the antibodies’ titers did not decrease after 60 days. The antibody response is directly proportional to the breastfed child’s age, but the amount of anti-RBD IgA decreases with the baby’s rank. The antibody response did not depend on the vaccine type, or on the mother’s age. Full article
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17 pages, 8441 KiB  
Systematic Review
The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis
by Ceria Halim, Audrey Fabianisa Mirza and Mutiara Indah Sari
Pathogens 2022, 11(2), 195; https://doi.org/10.3390/pathogens11020195 - 1 Feb 2022
Cited by 38 | Viewed by 3945
Abstract
Background: An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims [...] Read more.
Background: An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality. Methods: The design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar. Results: TNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178–1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259–1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130–1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004–1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010–1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = −5.0232; 95% CI 11.6832–1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103–2.6916; p = 0.34). Conclusion: IL-6 is an independent prognostic factor towards COVID-19 severity and mortality. Full article
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17 pages, 2526 KiB  
Article
Formation and Expansion of Memory B Cells against Coronavirus in Acutely Infected COVID-19 Individuals
by A. Karim Embong, Phuong Nguyen-Contant, Jiong Wang, Preshetha Kanagaiah, Francisco A. Chaves, Theresa F. Fitzgerald, Qian Zhou, Gabrielle Kosoy, Angela R. Branche, Benjamin L. Miller, Martin S. Zand, Mark Y. Sangster and David J. Topham
Pathogens 2022, 11(2), 186; https://doi.org/10.3390/pathogens11020186 - 29 Jan 2022
Cited by 3 | Viewed by 2773
Abstract
Infection with the β-coronavirus SARS-CoV-2 typically generates strong virus-specific antibody production. Antibody responses against novel features of SARS-CoV-2 proteins require naïve B cell activation, but there is a growing appreciation that conserved regions are recognized by pre-existing memory B cells (MBCs) generated by [...] Read more.
Infection with the β-coronavirus SARS-CoV-2 typically generates strong virus-specific antibody production. Antibody responses against novel features of SARS-CoV-2 proteins require naïve B cell activation, but there is a growing appreciation that conserved regions are recognized by pre-existing memory B cells (MBCs) generated by endemic coronaviruses. The current study investigated the role of pre-existing cross-reactive coronavirus memory in the antibody response to the viral spike (S) and nucleocapsid (N) proteins following SARS-CoV-2 infection. The breadth of reactivity of circulating antibodies, plasmablasts, and MBCs was analyzed. Acutely infected subjects generated strong IgG responses to the S protein, including the novel receptor binding domain, the conserved S2 region, and to the N protein. The response included reactivity to the S of endemic β-coronaviruses and, interestingly, to the N of an endemic α-coronavirus. Both mild and severe infection expanded IgG MBC populations reactive to the S of SARS-CoV-2 and endemic β-coronaviruses. Avidity of S-reactive IgG antibodies and MBCs increased after infection. Overall, findings indicate that the response to the S and N of SARS-CoV-2 involves pre-existing MBC activation and adaptation to novel features of the proteins, along with the potential of imprinting to shape the response to SARS-CoV-2 infection. Full article
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2021

Jump to: 2024, 2023, 2022

13 pages, 1468 KiB  
Article
Immunological and Genetic Investigation of SARS-CoV-2 Reinfection in an Otherwise Healthy, Young Marine Recruit
by Andrew G. Letizia, Catherine E. Arnold, Bishwo N. Adhikari, Logan J. Voegtly, Lindsay Glang, Gregory K. Rice, Carl W. Goforth, Megan A. Schilling, Dawn L. Weir, Francisco Malagon, Irene Ramos, Sindhu Vangeti, Ana S. Gonzalez-Reiche, Regina Z. Cer, Stuart C. Sealfon, Harm van Bakel and Kimberly A. Bishop-Lilly
Pathogens 2021, 10(12), 1589; https://doi.org/10.3390/pathogens10121589 - 8 Dec 2021
Cited by 1 | Viewed by 2814
Abstract
We used epidemiologic and viral genetic information to identify a case of likely reinfection in an otherwise healthy, young Marine recruit enrolled in the prospective, longitudinal COVID-19 Health Action Response for Marines (CHARM) study, and we paired these findings with serological studies. This [...] Read more.
We used epidemiologic and viral genetic information to identify a case of likely reinfection in an otherwise healthy, young Marine recruit enrolled in the prospective, longitudinal COVID-19 Health Action Response for Marines (CHARM) study, and we paired these findings with serological studies. This participant had a positive RT-PCR to SARS-CoV-2 upon routine sampling on study day 7, although he was asymptomatic at that time. He cleared the infection within seven days. On study day 46, he had developed symptoms consistent with COVID-19 and tested positive by RT-PCR for SARS-CoV-2 again. Viral whole genome sequencing was conducted from nares swabs at multiple time points. The day 7 sample was determined to be lineage B.1.340, whereas both the day 46 and day 49 samples were B.1.1. The first positive result for anti-SARS-CoV-2 IgM serology was collected on day 49 and for IgG on day 91. This case appears most consistent with a reinfection event. Our investigation into this case is unique in that we compared sequence data from more than just paired specimens, and we also assayed for immune response after both the initial infection and the later reinfection. These data demonstrate that individuals who have experienced an infection with SARS-CoV-2 may fail to generate effective or long-lasting immunity, similar to endemic human beta coronaviruses. Full article
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11 pages, 1110 KiB  
Review
Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form
by Annа Malkova, Igor Kudryavtsev, Anna Starshinova, Dmitry Kudlay, Yulia Zinchenko, Anzhela Glushkova, Piotr Yablonskiy and Yehuda Shoenfeld
Pathogens 2021, 10(11), 1408; https://doi.org/10.3390/pathogens10111408 - 30 Oct 2021
Cited by 63 | Viewed by 6585
Abstract
Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group [...] Read more.
Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The publications about COVID-19 which were published in online databases from December 2019 to September 2021 are analyzed in this review. According to the analysis, PCS develops on average in 30–60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage was revealed. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune disautonomia. Thus, the gender (female) and the presence of anosmia during an asymptomatic or mild course of the disease can be predictive factors for the development of PCS, which can be caused by autoimmune damage to neurons, glia, and cerebral vessels. Full article
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10 pages, 610 KiB  
Article
In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2
by Justine Defêche, Samira Azarzar, Alyssia Mesdagh, Patricia Dellot, Amandine Tytgat, Fabrice Bureau, Laurent Gillet, Yasmine Belhadj, Sebastien Bontems, Marie-Pierre Hayette, Raphaël Schils, Souad Rahmouni, Marie Ernst, Michel Moutschen and Gilles Darcis
Pathogens 2021, 10(11), 1362; https://doi.org/10.3390/pathogens10111362 - 21 Oct 2021
Cited by 11 | Viewed by 2368
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
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18 pages, 3252 KiB  
Article
Competing Bioaerosols May Influence the Seasonality of Influenza-Like Illnesses, including COVID-19. The Chicago Experience
by Richa B. Shah, Rachna D. Shah, Damien G. Retzinger, Andrew C. Retzinger, Deborah A. Retzinger and Gregory S. Retzinger
Pathogens 2021, 10(9), 1204; https://doi.org/10.3390/pathogens10091204 - 16 Sep 2021
Cited by 10 | Viewed by 3919
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
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17 pages, 2871 KiB  
Article
Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection
by Md. Aminul Islam, Leonardo Albarracin, Mikado Tomokiyo, Juan Carlos Valdez, Jacinto Sacur, Maria Guadalupe Vizoso-Pinto, Bruno G. N. Andrade, Rafael R. C. Cuadrat, Haruki Kitazawa and Julio Villena
Pathogens 2021, 10(9), 1197; https://doi.org/10.3390/pathogens10091197 - 15 Sep 2021
Cited by 13 | Viewed by 4026
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
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15 pages, 7568 KiB  
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
by Shashwat Sharad and Suman Kapur
Pathogens 2021, 10(9), 1130; https://doi.org/10.3390/pathogens10091130 - 2 Sep 2021
Cited by 12 | Viewed by 4246
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
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17 pages, 3260 KiB  
Article
Clinico-Genomic Analysis Reveals Mutations Associated with COVID-19 Disease Severity: Possible Modulation by RNA Structure
by Priyanka Mehta, Shanmukh Alle, Anusha Chaturvedi, Aparna Swaminathan, Sheeba Saifi, Ranjeet Maurya, Partha Chattopadhyay, Priti Devi, Ruchi Chauhan, Akshay Kanakan, Janani Srinivasa Vasudevan, Ramanathan Sethuraman, Subramanian Chidambaram, Mashrin Srivastava, Avinash Chakravarthi, Johnny Jacob, Madhuri Namagiri, Varma Konala, Sujeet Jha, U. Deva Priyakumar, P. K. Vinod and Rajesh Pandeyadd Show full author list remove Hide full author list
Pathogens 2021, 10(9), 1109; https://doi.org/10.3390/pathogens10091109 - 31 Aug 2021
Cited by 8 | Viewed by 4321
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
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10 pages, 1572 KiB  
Article
Acute Inflammatory Mediators in Young Adult Patients with COVID-19 in Mexico
by Anahí Maldonado-Cabrera, Aracely Angulo-Molina, Ubydul Haque, Carlos Velazquez, Andrea S. Álvarez-Villaseñor, Karla J. Santacruz-Gómez and Ana L. Gallego-Hernández
Pathogens 2021, 10(8), 1056; https://doi.org/10.3390/pathogens10081056 - 20 Aug 2021
Cited by 6 | Viewed by 3808
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
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12 pages, 1957 KiB  
Article
SARS-CoV-2 Seroprevalence and Neutralizing Antibody Response after the First and Second COVID-19 Pandemic Wave in Croatia
by Tatjana Vilibic-Cavlek, Vladimir Stevanovic, Maja Ilic, Ljubo Barbic, Krunoslav Capak, Irena Tabain, Jasna Lenicek Krleza, Thomas Ferenc, Zeljka Hruskar, Renata Zrinski Topic, Vanja Kaliterna, Arlen Antolovic-Pozgain, Jasmina Kucinar, Iva Koscak, Dijana Mayer, Mario Sviben, Ljiljana Antolasic, Ljiljana Milasincic, Lovro Bucic, Ivana Ferencak and Bernard Kaicadd Show full author list remove Hide full author list
Pathogens 2021, 10(6), 774; https://doi.org/10.3390/pathogens10060774 - 20 Jun 2021
Cited by 19 | Viewed by 4817
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
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11 pages, 1003 KiB  
Communication
Dolosigranulum pigrum Modulates Immunity against SARS-CoV-2 in Respiratory Epithelial Cells
by Md. Aminul Islam, Leonardo Albarracin, Vyacheslav Melnikov, Bruno G. N. Andrade, Rafael R. C. Cuadrat, Haruki Kitazawa and Julio Villena
Pathogens 2021, 10(6), 634; https://doi.org/10.3390/pathogens10060634 - 21 May 2021
Cited by 12 | Viewed by 4707
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
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16 pages, 1482 KiB  
Article
Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice
by Appavu K. Sundaram, Daniel Ewing, Zhaodong Liang, Vihasi Jani, Ying Cheng, Peifang Sun, Kanakatte Raviprakash, Shuenn-Jue Wu, Nikolai Petrovsky, Gabriel Defang, Maya Williams and Kevin R. Porter
Pathogens 2021, 10(5), 626; https://doi.org/10.3390/pathogens10050626 - 19 May 2021
Cited by 9 | Viewed by 5199
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
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