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Journal ArticleDOI

Adaptive immune responses to SARS-CoV-2.

01 May 2021-Advanced Drug Delivery Reviews (Elsevier BV)-Vol. 172, pp 1-8
TL;DR: In this paper, a review of adaptive immune responses against SARS-CoV-2, the coronavirus that causes COVID-19, is presented, focusing on the role of antibody and T-cell responses.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2021-05-01 and is currently open access. It has received 6 citations till now. The article focuses on the topics: Immune system.
Citations
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Journal ArticleDOI
TL;DR: In this article , a cross-sectional and longitudinal study, blood-derived MBC and MTC responses were evaluated in 68 anti-spike IgG-positive mild coronavirus disease 2019 (COVID-19) convalescents at visit 1, between 1 and 7 months (median 4.1 months) after disease onset.

18 citations

Journal ArticleDOI
TL;DR: How cellular immunity is the axis around which the rest of the immune system components revolve is discussed, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells.
Abstract: Two years after the appearance of the SARS-CoV-2 virus, the causal agent of the current global pandemic, it is time to analyze the evolution of the immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity and the resolution of infection. The early appearance, breadth and magnitude of SARS-CoV-2 specific T cell response has been correlated with disease severity and it has been thought that T cell responses may be sufficient to clear infection with minimal disease in COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia. However, our knowledge of the phenotypic and functional diversity of CD8+ cytotoxic lymphocytes, CD4+ T helper cells, mucosal-associated invariant T (MAIT) cells and CD4+ T follicular helper (Tfh), which play a critical role in infection control as well as long-term protection, is still evolving. It has been described how CD8+ cytotoxic lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ and TNF-α) and directly killing infected cells, negatively correlating with stages of disease progression. In addition, CD4+ T helper cells have been reported to be key pieces, leading, coordinating and ultimately regulating antiviral immunity. For instance, in some more severe COVID-19 cases a dysregulated CD4+ T cell signature may contribute to the greater production of pro-inflammatory cytokines responsible for pathogenic inflammation. Here we discuss how cellular immunity is the axis around which the rest of the immune system components revolve, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells. This review also analyses the critical role of cellular immunity in modulating the development of high-affinity neutralizing antibodies and germinal center B cell differentiation in memory and long-lived antibody secreting cells. Finally, since there is currently a high percentage of vaccinated population and, in some cases, vaccine booster doses are even being administered in certain countries, we have also summarized newer approaches to long-lasting protective immunity and the cross-protection of cellular immune response against SARS-CoV-2.

16 citations

Journal ArticleDOI
01 May 2022-Vaccines
TL;DR: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response, and related to a trained immunity profile.
Abstract: Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 108 CFU or one dose of 1 × 105 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4+ and CD8+ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.

8 citations

Journal ArticleDOI
TL;DR: Understanding the crosstalk between RNF proteins and SARS‐CoV‐2 infection would help design potential novel targets for COVID‐19 treatment and discuss the diverse antiviral mechanisms of R NF proteins and viral immune evasion in an RNF protein‐dependent manner.
Abstract: The pandemic coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is currently the most formidable challenge to humankind. Understanding the complicated virus‐host interplay is crucial for fighting against viral infection. A growing number of studies point to the critical roles of RING (really interesting new gene) finger (RNF) proteins during SARS‐CoV‐2 infection. RNF proteins exert direct antiviral activity by targeting genome and envelope glycoproteins of SARS‐CoV‐2. Additionally, some RNF members serve as potent regulators for antiviral innate immunity and antibody‐dependent neutralization of SARS‐CoV‐2. Notably, SARS‐CoV‐2 also hijacks the RNF proteins‐mediated ubiquitination process to evade host antiviral innate immunity and enhance viral replication. In this mini‐review, we discuss the diverse antiviral mechanisms of RNF proteins and viral immune evasion in an RNF proteins‐dependent manner. Understanding the crosstalk between RNF proteins and SARS‐CoV‐2 infection would help design potential novel targets for COVID‐19 treatment.

4 citations

Journal ArticleDOI
TL;DR: A dendritic cell-based vaccine for SARS-CoV-2 has the potential to be an effective vaccine that solves existing problems and is summarized by summarizing the crucial role of dendedritic cells in the formation of T cell immunity.
Abstract: Finding a vaccine that can last a long time and effective against viruses with high mutation rates such as SARS-CoV-2 is still a challenge today. The various vaccines that have been available have decreased in effectiveness and require booster administration. As the professional antigen presenting cell, Dendritic Cells can also activate the immune system, especially T cells. This ability makes dendritic cells have been developed as vaccines for some types of diseases. In SARS-CoV-2 infection, T cells play a vital role in eliminating the virus, and their presence can be detected in the long term. Hence, this condition shows that the formation of T cell immunity is essential to prevent and control the course of the disease. The construction of vaccines oriented to induce strong T cells response can be formed by utilizing dendritic cells. In this article, we discuss and illustrate the role of dendritic cells and T cells in the pathogenesis of SARS-CoV-2 infection and summarizing the crucial role of dendritic cells in the formation of T cell immunity. We arrange the basis concept of developing dendritic cells for SARS-CoV-2 vaccines. A dendritic cell-based vaccine for SARS-CoV-2 has the potential to be an effective vaccine that solves existing problems.

1 citations

References
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Journal ArticleDOI
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.

36,578 citations

Journal ArticleDOI
01 Apr 2020-Nature
TL;DR: Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
Abstract: Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

5,840 citations

Journal ArticleDOI
TL;DR: The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production, which may be of importance due to their correlation with disease severity in COVID-19.
Abstract: BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

3,488 citations

Journal ArticleDOI
25 Jun 2020-Cell
TL;DR: Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS.

3,043 citations

Journal ArticleDOI
TL;DR: It is suggested that SARS-CoV2-specific IgG or IgM seroconversion occurs within 20 days post symptom onset and may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.
Abstract: We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

2,473 citations