Viruses

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22 pages, 3342 KiB

Open AccessArticle

Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach

by Anna Maria Fratta Pasini, Chiara Stranieri, Edoardo Giuseppe Di Leo, Lorenzo Bertolone, Antonino Aparo, Fabiana Busti, Annalisa Castagna, Alice Vianello, Fabio Chesini, Simonetta Friso, Domenico Girelli and Luciano Cominacini

Viruses 2025, 17(3), 359; https://doi.org/10.3390/v17030359 - 28 Feb 2025

Viewed by 674

Abstract

This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia [...] Read more.

This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (p < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (p < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (p < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (p < 0.0005, p < 0.05 and p < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (p < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH’s critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort. Full article

(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)

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16 pages, 4916 KiB

Open AccessArticle

Immunogenic Potential of Selected Peptides from SARS-CoV-2 Proteins and Their Ability to Block S1/ACE-2 Binding

by Lara Cristina da Silva Lima, Thiago Demetrius Woiski, Juliana Ferreira de Moura, Roberto Rosati, João Carlos Minozzo, Emeline Huk da Silva, Aline Castro Rodrigues Lucena, Bruno Cezar Antunes, Sérgio Caldas, Myrian Morato Duarte, Maurício Abreu Santos, Rubens Luiz Ferreira Gusso, Erickson Luiz de Moura, Ana Paula Santos Silva, Luciana Potzecki, Daniele Maria Ferreira, Elizabeth Soares Fernandes, Bonald Cavalcante de Figueiredo and Lauro Mera de Souza

Viruses 2025, 17(2), 165; https://doi.org/10.3390/v17020165 - 24 Jan 2025

Viewed by 793

Abstract

The first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the coronavirus disease 2019 (COVID-19), occurred in December 2019. Within a single month, the disease reached other countries, spreading in a rapid and generalized manner worldwide to cause [...] Read more.

The first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the coronavirus disease 2019 (COVID-19), occurred in December 2019. Within a single month, the disease reached other countries, spreading in a rapid and generalized manner worldwide to cause the COVID-19 pandemic. In Brazil, the number of COVID-19 cases surpassed 38 million. This study was conducted to produce antibodies against SARS-CoV-2 and investigate the immunogenic potential of synthetic peptides containing partial sequences of the main proteins (spike, membrane, and nucleocapsid proteins). In addition, we evaluated the ability of the antibodies to impair the interaction between the spike S1 protein and human ACE-2 protein, which is the main route of entry of the virus into host cells. By immunizing horses with synthetic peptides, we obtained hyperimmune sera with specific anti-SARS-CoV-2 antibodies, which were fragmented to release the F(ab’)2 portion that binds to the different SARS-CoV-2 proteins as a recombinant S1-protein and proteins from a viral lysate. The other F(ab’)2 samples also impaired the interaction between S1 protein and ACE-2 proteins, showing high potential to prevent viral spreading. Full article

(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)

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15 pages, 2358 KiB

Open AccessArticle

The Ability of Combined Flavonol and Trihydroxyorganic Acid to Suppress SARS-CoV-2 Reproduction

by Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Vladimir Berezin, Irina Zaitseva, Elmira Omirtaeva, Adolat Manakbayeva, Yergali Moldakhanov, Elmira Anarkulova, Anar Imangazy, Kuralay Akanova, Zhumagali Koshemetov, Nurkul Orazymbetova and Bakyt Umuraliyev

Viruses 2025, 17(1), 37; https://doi.org/10.3390/v17010037 - 30 Dec 2024

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Abstract

The global burden of COVID-19 continues to rise, and despite significant progress in vaccine development, there remains a critical need for effective treatments for the severe inflammation and acute lung injury associated with SARS-CoV-2 infection. In this study, we explored the antiviral properties [...] Read more.

The global burden of COVID-19 continues to rise, and despite significant progress in vaccine development, there remains a critical need for effective treatments for the severe inflammation and acute lung injury associated with SARS-CoV-2 infection. In this study, we explored the antiviral properties of a plant-derived complex consisting of flavonol and hydroxyorganic acid compounds. Our research focused on the ability of the flavonol and hydroxyorganic acid complex to suppress the activity of several key proteins involved in the replication and maturation of SARS-CoV-2. These proteins include ACE2 protein, HRV 3C Protease, and Mpro (Main Protease). It was shown that the plant-based complex effectively inhibited the activity of these viral proteins. In addition to its effects on viral proteins, the flavonol and hydroxyorganic acid complex were shown to suppress viral replication in Vero E6 cells. At a dose of 22 μg/mL, the drug demonstrated maximum antiviral activity, significantly reducing the replication of SARS-CoV-2 in vitro. In preliminary studies, the complex showed both prophylactic and therapeutic potential, suggesting that it may be useful for preventing infection, as well as reducing the severity of disease once an individual has been infected with SARS-CoV-2. Based on the compelling results of this study, we propose the flavonol and hydroxyorganic acid complex as a potential therapeutic compound for SARS-CoV-2. Its ability to inhibit key viral proteins, suppress viral replication and exhibit protective and therapeutic effects positions it as a valuable candidate for further research and clinical evaluation. As the global fight against SARS-CoV-2 continues, plant-based therapies like this complex could complement existing treatments and provide new options for managing and treating the disease. Full article

(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)

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9 pages, 262 KiB

Open AccessCommunication

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

Cited by 2 | Viewed by 1689

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

Open AccessArticle

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 2159

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)

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15 pages, 1958 KiB

Open AccessArticle

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. Show full author list Hide full author list

Viruses 2023, 15(2), 530; https://doi.org/10.3390/v15020530 - 14 Feb 2023

Cited by 4 | Viewed by 3135

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)

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11 pages, 1700 KiB

Open AccessArticle

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 12 | Viewed by 2859

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⁺CD127^low 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⁺CD127^low 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)

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10 pages, 2907 KiB

Open AccessArticle

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 61 | Viewed by 4839

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)

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10 pages, 2414 KiB

Open AccessEditor’s ChoiceCommunication

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 17 | Viewed by 4419

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)

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Graphical abstract

10 pages, 1343 KiB

Open AccessCommunication

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 9 | Viewed by 3590

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)

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Review

Jump to: Research, Other

27 pages, 859 KiB

Open AccessReview

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 34 | Viewed by 7663

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)

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Other

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8 pages, 713 KiB

Open AccessBrief 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

Cited by 4 | Viewed by 1863

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)

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