Basic Sciences for the Conquest of COVID-19

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: 30 September 2024 | Viewed by 24100

Special Issue Editors


E-Mail Website
Guest Editor
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan
Interests: HIV-1; restriction factors; SARS-CoV-2 variants

E-Mail Website
Guest Editor
Department of Microbiology, Université Laval, Quebec City, QC G1V0A6, Canada
Interests: infectious diseases; immune responses; apoptosis

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic—caused by SARS-CoV-2, which is phylogenetically derived from animal coronaviruses—is a once-in-a-century disaster. Since the emergence of this zoonotic virus, a growing number of scientists all over the world have been tackling this global crisis as a matter of urgency, attempting to conquer this killer virus that threatens billions of lives. Thus, the international power of science has led to a tremendous number of informative results in a short period of time.

This Special Issue of Viruses will cover 1) SARS-CoV-2 replication mechanisms through host–virus interactions, including cell entry, RNA replication, viral protein synthesis, and virus production; 2) infection-induced innate immunity, cell signaling, and cell damage; 3) the viral pathogenicity of different variant strains, represented by clinical outcomes and immune responses in humans; 4) SARS-CoV-2 infection in several different animal models; 5) therapeutic approaches, such as vaccines, antiviral drugs, passive immunization, and inflammation inhibitors, among others.

Original articles, comprehensive reviews, short communications, and new perspectives are welcome.

Dr. Kenzo Tokunaga
Dr. Jérôme Estaquier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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
  • host–pathogen interactions
  • virus replication
  • immune response
  • viral pathogenicity
  • animal models
  • therapeutic strategies

Published Papers (9 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

9 pages, 262 KiB  
Communication
Association of the IFNG +874T/A Polymorphism with Symptomatic COVID-19 Susceptibility
by Kevin Matheus Lima de Sarges, Flávia Póvoa da Costa, Erika Ferreira dos Santos, Marcos Henrique Damasceno Cantanhede, Rosilene da Silva, Adriana de Oliveira Lameira Veríssimo, Maria de Nazaré do Socorro de Almeida Viana, Fabíola Brasil Barbosa Rodrigues, Mauro de Meira Leite, Maria Karoliny da Silva Torres, Christiane Bentes da Silva, Mioni Thieli Figueiredo Magalhães de Brito, Andréa Luciana Soares da Silva, Daniele Freitas Henriques, Izaura Maria Vieira Cayres Vallinoto, Giselle Maria Rachid Viana, Maria Alice Freitas Queiroz, Antonio Carlos Rosário Vallinoto and Eduardo José Melo dos Santos
Viruses 2024, 16(4), 650; https://doi.org/10.3390/v16040650 - 22 Apr 2024
Viewed by 610
Abstract
Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, [...] Read more.
Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
11 pages, 1009 KiB  
Article
Factors Associated with Neutralizing Antibody Responses following 2-Dose and 3rd Booster Monovalent COVID-19 Vaccination in Japanese People Living with HIV
by Isaac Ngare, Toong Seng Tan, Mako Toyoda, Takeo Kuwata, Soichiro Takahama, Eriko Nakashima, Naoya Yamasaki, Chihiro Motozono, Teruhisa Fujii, Rumi Minami, Godfrey Barabona and Takamasa Ueno
Viruses 2024, 16(4), 555; https://doi.org/10.3390/v16040555 - 2 Apr 2024
Viewed by 1063
Abstract
People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese [...] Read more.
People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

15 pages, 1958 KiB  
Article
Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron
by Linhui Hao, Tien-Ying Hsiang, Ronit R. Dalmat, Renee Ireton, Jennifer F. Morton, Caleb Stokes, Jason Netland, Malika Hale, Chris Thouvenel, Anna Wald, Nicholas M. Franko, Kristen Huden, Helen Y. Chu, Alex Sigal, Alex L. Greninger, Sasha Tilles, Lynn K. Barrett, Wesley C. Van Voorhis, Jennifer Munt, Trevor Scobey, Ralph S. Baric, David J. Rawlings, Marion Pepper, Paul K. Drain and Michael Gale, Jr.add Show full author list remove Hide full author list
Viruses 2023, 15(2), 530; https://doi.org/10.3390/v15020530 - 14 Feb 2023
Cited by 2 | Viewed by 2192
Abstract
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline [...] Read more.
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

11 pages, 1700 KiB  
Article
Regulatory T Cells Decreased during Recovery from Mild COVID-19
by Purilap Seepathomnarong, Jomkwan Ongarj, Ratchanon Sophonmanee, Bunya Seeyankem, Sarunyou Chusri, Smonrapat Surasombatpattana and Nawamin Pinpathomrat
Viruses 2022, 14(8), 1688; https://doi.org/10.3390/v14081688 - 30 Jul 2022
Cited by 10 | Viewed by 2104
Abstract
Depending on the intensity and duration of SARS-CoV-2 infection, the host immune response plays a significant role in immunological protection. Here, we studied the regulatory T-cell (Treg) response in relation to kinetic change and cytokine production in patients with mild COVID-19. Nineteen SARS-CoV-2-positive [...] Read more.
Depending on the intensity and duration of SARS-CoV-2 infection, the host immune response plays a significant role in immunological protection. Here, we studied the regulatory T-cell (Treg) response in relation to kinetic change and cytokine production in patients with mild COVID-19. Nineteen SARS-CoV-2-positive patients were recruited, and blood was collected at four time points, i.e., seven days after admission, after discharge, and one and three months after recovery. CD3+CD4+CD25+CD127low was marked as the Treg population, with IL-10 and TGF-β used to study cytokine-producing Tregs. IFN-γ-producing CD8+ T cells were observed for an effector response. The Treg percentage in patients with mild COVID-19 increased during hospitalization compared to during the recovery period. Peripheral blood mononuclear cells (PBMCs) were quantified, and the T-cell response was characterized by re-stimulation with S1 and N peptides. IL-10 and TGF-β were produced by CD25+CD127low T cells during the active infection phase, especially with N peptide stimulation. Compared to N peptide stimulation, S1 peptide stimulation provided superior IFN-γ-secreting CD8+ T-cell responses. Our results suggest that while IFN-γ+CD8+ T cells confer antiviral immunity, cytokine-producing Tregs may have a substantial role in regulating inflammatory responses in mild SARS-CoV-2 infection. Novel vaccine development may also consider enhancing T-cell repertoires. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

10 pages, 2907 KiB  
Article
Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies
by Hao Zhou, Belinda M. Dcosta, Nathaniel R. Landau and Takuya Tada
Viruses 2022, 14(6), 1334; https://doi.org/10.3390/v14061334 - 18 Jun 2022
Cited by 51 | Viewed by 3741
Abstract
The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous [...] Read more.
The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

10 pages, 2414 KiB  
Communication
Evolution of Anti-RBD IgG Avidity following SARS-CoV-2 Infection
by Alexandra Tauzin, Gabrielle Gendron-Lepage, Manon Nayrac, Sai Priya Anand, Catherine Bourassa, Halima Medjahed, Guillaume Goyette, Mathieu Dubé, Renée Bazin, Daniel E. Kaufmann and Andrés Finzi
Viruses 2022, 14(3), 532; https://doi.org/10.3390/v14030532 - 4 Mar 2022
Cited by 15 | Viewed by 3450
Abstract
SARS-CoV-2 infection rapidly elicits anti-Spike antibodies whose quantity in plasma gradually declines upon resolution of symptoms. This decline is part of the evolution of an immune response leading to B cell differentiation into short-lived antibody-secreting cells or resting memory B cells. At the [...] Read more.
SARS-CoV-2 infection rapidly elicits anti-Spike antibodies whose quantity in plasma gradually declines upon resolution of symptoms. This decline is part of the evolution of an immune response leading to B cell differentiation into short-lived antibody-secreting cells or resting memory B cells. At the same time, the ongoing class switch and antibody maturation processes occurring in germinal centers lead to the selection of B cell clones secreting antibodies with higher affinity for their cognate antigen, thereby improving their functional activity. To determine whether the decline in SARS-CoV-2 antibodies is paralleled with an increase in avidity of the anti-viral antibodies produced, we developed a simple assay to measure the avidity of anti-receptor binding domain (RBD) IgG elicited by SARS-CoV-2 infection. We longitudinally followed a cohort of 29 convalescent donors with blood samples collected between 6- and 32-weeks post-symptoms onset. We observed that, while the level of antibodies declines over time, the anti-RBD avidity progressively increases and correlates with the B cell class switch. Additionally, we observed that anti-RBD avidity increased similarly after SARS-CoV-2 mRNA vaccination and after SARS-CoV-2 infection. Our results suggest that anti-RBD IgG avidity determination could be a surrogate assay for antibody affinity maturation and, thus, suitable for studying humoral responses elicited by natural infection and/or vaccination. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Graphical abstract

10 pages, 1343 KiB  
Communication
Antigenicity of the Mu (B.1.621) and A.2.5 SARS-CoV-2 Spikes
by Debashree Chatterjee, Alexandra Tauzin, Annemarie Laumaea, Shang Yu Gong, Yuxia Bo, Aurélie Guilbault, Guillaume Goyette, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Jonathan Richard, Sandrine Moreira, Marceline Côté and Andrés Finzi
Viruses 2022, 14(1), 144; https://doi.org/10.3390/v14010144 - 14 Jan 2022
Cited by 8 | Viewed by 2861
Abstract
The rapid emergence of SARS-CoV-2 variants is fueling the recent waves of the COVID-19 pandemic. Here, we assessed ACE2 binding and antigenicity of Mu (B.1.621) and A.2.5 Spikes. Both these variants carry some mutations shared by other emerging variants. Some of the pivotal [...] Read more.
The rapid emergence of SARS-CoV-2 variants is fueling the recent waves of the COVID-19 pandemic. Here, we assessed ACE2 binding and antigenicity of Mu (B.1.621) and A.2.5 Spikes. Both these variants carry some mutations shared by other emerging variants. Some of the pivotal mutations such as N501Y and E484K in the receptor-binding domain (RBD) detected in B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) are now present within the Mu variant. Similarly, the L452R mutation of B.1.617.2 (Delta) variant is present in A.2.5. In this study, we observed that these Spike variants bound better to the ACE2 receptor in a temperature-dependent manner. Pseudoviral particles bearing the Spike of Mu were similarly neutralized by plasma from vaccinated individuals than those carrying the Beta (B.1.351) and Delta (B.1.617.2) Spikes. Altogether, our results indicate the importance of measuring critical parameters such as ACE2 interaction, plasma recognition and neutralization ability of each emerging variant. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

Review

Jump to: Research, Other

27 pages, 859 KiB  
Review
SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion
by Zheng Yao Low, Nur Zawanah Zabidi, Ashley Jia Wen Yip, Ashwini Puniyamurti, Vincent T. K. Chow and Sunil K. Lal
Viruses 2022, 14(9), 1991; https://doi.org/10.3390/v14091991 - 8 Sep 2022
Cited by 23 | Viewed by 5535
Abstract
Coronavirus disease 2019 (COVID-19) has caused an unprecedented global crisis and continues to threaten public health. The etiological agent of this devastating pandemic outbreak is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by delayed immune responses, followed by exaggerated inflammatory responses. [...] Read more.
Coronavirus disease 2019 (COVID-19) has caused an unprecedented global crisis and continues to threaten public health. The etiological agent of this devastating pandemic outbreak is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by delayed immune responses, followed by exaggerated inflammatory responses. It is well-established that the interferon (IFN) and JAK/STAT signaling pathways constitute the first line of defense against viral and bacterial infections. To achieve viral replication, numerous viruses are able to antagonize or hijack these signaling pathways to attain productive infection, including SARS-CoV-2. Multiple studies document the roles of several non-structural proteins (NSPs) of SARS-CoV-2 that facilitate the establishment of viral replication in host cells via immune escape. In this review, we summarize and highlight the functions and characteristics of SARS-CoV-2 NSPs that confer host immune evasion. The molecular mechanisms mediating immune evasion and the related potential therapeutic strategies for controlling the COVID-19 pandemic are also discussed. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

Other

Jump to: Research, Review

8 pages, 713 KiB  
Brief Report
Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019
by Chie Yamamoto, Masashi Taniguchi, Keitaro Furukawa, Toru Inaba, Yui Niiyama, Daisuke Ide, Shinsuke Mizutani, Junya Kuroda, Yoko Tanino, Keisuke Nishioka, Yohei Watanabe, Koichi Takayama, Takaaki Nakaya and Yoko Nukui
Viruses 2024, 16(5), 718; https://doi.org/10.3390/v16050718 - 30 Apr 2024
Viewed by 603
Abstract
Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [...] Read more.
Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapies have considerable clinical implications. We present a patient who independently acquired a T21I mutation in the 3CL protease after nirmatrelvir exposure. The T21I mutation in the 3CL protease is one of the most frequent mutations responsible for nirmatrelvir resistance. However, limited reports exist on actual cases of SARS-CoV-2 with T21I and other mutations in the 3CL protease. The patient, a 55 year-old male, had COVID-19 during chemotherapy for multiple myeloma. He was treated with nirmatrelvir early in the course of the disease but relapsed, and SARS-CoV-2 with a T21I mutation in the 3CL protease was detected in nasopharyngeal swab fluid. The patient had temporary respiratory failure but later recovered well. During treatment with remdesivir and dexamethasone, viruses with the T21I mutation in the 3CL protease showed a decreasing trend during disease progression while increasing during improvement. The impact of drug-resistant SARS-CoV-2 on the clinical course, including its severity, remains unknown. Our study is important for examining the clinical impact of nirmatrelvir resistance in COVID-19. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
Show Figures

Figure 1

Back to TopTop