scholarly journals Immune Responses against SARS-CoV-2—Questions and Experiences

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1342
Author(s):  
Harald Mangge ◽  
Markus Kneihsl ◽  
Wolfgang Schnedl ◽  
Gerald Sendlhofer ◽  
Francesco Curcio ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Immune Reactivity ◽  
Fatigue Syndrome ◽  
Open Questions ◽  
Systemic Symptoms

Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else (“sterilizing” immunity). Others produce antibodies and do not get COVID-19 but transmit the virus to others (“protective” immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune–vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, herein we discuss important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories.

scholarly journals Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

2011 ◽  
Vol 19 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Jin Huk Choi ◽  
Joe Dekker ◽  
Stephen C. Schafer ◽  
Jobby John ◽  
Craig E. Whitfill ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Transduction Efficiency ◽  
Virus Antibody ◽  
Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

scholarly journals Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

2018 ◽  
Author(s):  
Felix G. Delgado ◽  
Karina I. Torres ◽  
Jaime E. Castellanos ◽  
Consuelo Romero-Sánchez ◽  
Etienne Simon-Lorière ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses ◽  
B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

scholarly journals 578. INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S390-S391
Author(s):  
Viviane M Andrade ◽  
Aaron Christensen-Quick ◽  
Joseph Agnes ◽  
Jared Tur ◽  
Charles C Reed ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Stock Options ◽  
Neutralizing Antibodies ◽  
Cell Activity ◽  
Cellular Responses ◽  
Neutralization Assay ◽  
Material Support ◽  
Fold Reduction

Abstract Background Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with increased transmissibility, disease severity, and resistance to neutralization by current vaccines under emergency use authorization (EUA). Here we assessed cross-immune responses of INO-4800 vaccinated subjects against SARS-CoV-2 VOCs. Methods We used a SARS-CoV-2 IgG ELISA and a pseudo neutralization assay to assess humoral responses, and an IFNγ ELISpot to measure cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. Results IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO-4800 (Figure 1a). We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of either 0.5 mg, 1 mg, or 2 mg of INO-4800. Neutralization was detected against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70-729), 295 (range: 46-886), 105 (range: 25-309), and 664 (range: 25-2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant (Figure 1b). Next, we compared cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO-4800 vaccination. We observed similar cellular responses to WT (median = 82.2 IQR = 58.9-205.3), B.1.1.7 (79.4, IQR = 38.9- 179.7), B.1.351 (80, IQR = 40.0-208.6) and P.1 (78.3, IQR = 53.1-177.8) Spike peptides (Figure 2). Conclusion INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested. Disclosures Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Joseph Agnes, PhD, Inovio (Employee, Shareholder) Jared Tur, PhD, Inovio (Employee) Charles C. Reed, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Richa Kalia, MS, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, I have stock options with Inovio Pharmaceuticals as an employee.) Idania Marrero, MD, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Dustin Elwood, PhD, Inovio Pharmaceuticals (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Trevor McMullan, MSc, Inovio (Shareholder) Patrick Pezzoli, BS, Inovio (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Albert Sylvester, MS, Inovio (Employee, Shareholder) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Jean Boyer, PhD, Inovio (Employee) Kate Broderick, PhD, Inovio (Employee)

scholarly journals Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2369-2379
Author(s):  
Tatyana Pozner ◽  
Martin Regensburger ◽  
Tobias Engelhorn ◽  
Jürgen Winkler ◽  
Beate Winner
Keyword(s):  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Lower Limbs ◽  
Pathogenic Variants ◽  
Structural Abnormalities ◽  
Neuronal Systems ◽  
And Function ◽  
The Impact

Abstract Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders.

scholarly journals Sequential Immunization with Universal Live Attenuated Influenza Vaccine Candidates Protects Ferrets against a High-Dose Heterologous Virus Challenge

2018 ◽  
Author(s):  
Irina Isakova-Sivak ◽  
Victoria Matyushenko ◽  
Tatiana Kotomina ◽  
Irina Kiseleva ◽  
Elena Krutikova ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Cd8 T Cell ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Control Group ◽  
High Dose ◽  
T Cell Immune Responses

The development of universal influenza vaccines, i.e. vaccines that can provide broad protection against seasonal and potentially pandemic influenza viruses, has been a priority for more than 20 years. Several approaches have been proposed that redirect the adaptive immune responses from immunodominant hypervariable regions to low-immunogenic but highly conserved regions of viral proteins. Here we induced broadly reactive anti-hemagglutinin (HA) stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HA (cHA). These vaccines contained the HA stalk domain from H1N1pdm09 virus but antigenically unrelated globular head domains from avian influenza viruses H5N1, H8N4 and H9N2. In addition, the source of the viral nucleoprotein (NP) of the LAIV strains was changed from A/Leningrad/17 master donor virus (MDV) to wild-type (WT) H1N1pdm09 virus, in order to induce CD8 T-cell immune responses more relevant to current infections. To avoid any difference in protective effect of the various anti-neuraminidase (NA) antibodies, all LAIVs were engineered to contain the NA gene of Len/17 MDV. Naïve ferrets were immunized with three doses of (i) classical LAIVs containing non-chimeric HA and NP from MDV (LAIVs (NP-MDV)); (ii) cHA-based LAIVs containing NP from MDV (cHA LAIVs (NP-MDV)); and (iii) cHA-based LAIVs containing NP from H1N1pdm09 virus (cHA LAIVs (NP-WT)). A high-dose challenge with H1N1pdm09 virus induced significant pathology in the control, non-immunized ferrets, including high virus titers in respiratory tissues, clinical signs of disease and histopathological changes in nasal turbinates and lung tissues. All three vaccination regimens protected animals from clinical manifestations of disease: immunized ferrets did not lose weight or show clinical symptoms, and their fever was significantly lower than in the control group. Further analysis of virological and pathological data revealed the following hierarchy in the cross-protective efficacy of the vaccines: cHA LAIVs (NP-WT) > cHA LAIVs (NP-MDV) > LAIVs (NP-MDV). This ferret study showed that prototype universal LAIVs that combine the two approaches of inducing anti-HA stalk antibody and more relevant CD8 T-cell immune responses are highly promising candidates for further clinical development.

scholarly journals Coronavirus Disease 2019 (COVID-19): Pathogenesis, Immune Responses, and Treatment Options

2020 ◽  
Author(s):  
Nandini Eswaran ◽  
Shwetha Krishna
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Defense Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Evolutionary Process ◽  
Effective Vaccine ◽  
Novel Coronavirus

Background: The emergence and the spread of the novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating impact on the economy and has become a pressing issue globally. Due to the significant increase in the number of confirmed cases and death tolls worldwide, and certain countries reporting second waves, there is an immediate need for an effective vaccine or other therapeutic intervention to control the spread of the disease. Improving our understanding on the host’s anti-viral immune response on SARS-CoV-2 infection, the potential immune evasion mechanisms adopted by the virus, and the speculated role of antibody dependent enhancement (ADE) in coronavirus disease 2019 (COVID-19) pathogenesis will aid in identifying and designing effective therapeutics. Aim: This review aims to provide an in-depth view of the current knowledge available on the range of host defense mechanisms activated by SARS-CoV-2 infection and various immune evasion mechanisms utilized by the virus. In addition, it also highlights the postulated role of ADE in viral pathogenesis and covers the different preventive and therapeutic options available for the treatment of COVID-19 based on current literature. Discussion: The ongoing COVID-19 pandemic serves as a timely reminder on the constant evolutionary process the virus undergoes to emerge as a novel strain and to spread undetected within the population. Similar to other infectious diseases, the host defence mechanism is triggered, and it plays a central role in dampening viral replication by recruiting immune cells and activating anti-viral mechanisms to control the spread of infection by SARS-CoV-2. However, the virus has adopted different immune evasion mechanisms to circumvent host surveillance to successfully establish infection. Hence, understanding the host’s immune responses triggered by SARS-CoV-2 infection is critical for identifying and designing novel and effective therapeutics. Currently, over 70% of the population are either asymptomatic or they showcase mild to moderate symptoms and reasons for why some people can mount immune responses more quickly than others are unknown. However, a growing body of research speculates that the ADE mechanism may facilitate the SARS-CoV-2 entry and can contribute to severe clinical manifestations. With the constant rise in the number of confirmed cases, there is an immediate need for an effective vaccine to mitigate the spread of the virus. Presently, there is no treatment for COVID-19 although several vaccine candidates are in clinical trials. Therefore, preventive measures like social distancing, isolation, and travel restrictions, may be the key to controlling the rapid spread of COVID-19.

scholarly journals Interdependencies between cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination

2021 ◽  
Author(s):  
Moritz M Hollstein ◽  
Lennart Muensterkoetter ◽  
Michael P Schoen ◽  
Armin Bergmann ◽  
Thea M Husar ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Booster Vaccination ◽  
Antibody Avidity ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune

Background: Homologous and heterologous SARS-CoV-2-vaccinations yield different spike protein-directed humoral and cellular immune responses. However, their interdependencies remain elusive. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received homologous vaccination with Astra (ChAdOx1-S; AstraZeneca) or BNT (BNT162b2; Biontech/Pfizer) or heterologous vaccination with Astra/BNT. We assessed the humoral (anti-spike-RBD-IgG, neutralizing antibodies, antibody avidity) and cellular (spike-induced T cell interferon-y release) immune response in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Findings: Initial vaccination with Astra resulted in lower anti-spike-RBD-IgG responses compared to BNT (70+/-114 vs. 226+/-279 BAU/ml, p<0.01) at T1, whereas T cell activation did not differ significantly. Booster vaccination with BNT proved superior to Astra at T2 (anti-spike-RBD-IgG: Astra/BNT 2387+/-1627 and BNT/BNT 3202+/-2184 vs. Astra/Astra 413+/-461 BAU/ml, both p<0.001; spike-induced T cell interferon-y; release: Astra/BNT 5069+/-6733 and BNT/BNT 4880+/-7570 vs. Astra/Astra 1152+/-2243 mIU/ml, both p<0.001). No significant differences were detected between BNT-boostered groups at T2. For Astra, we observed no booster effect on T cell activation. We found associations between anti-spike-RBD-IgG levels (Astra/BNT and BNT/BNT) and T cell responses (Astra/Astra and Astra/BNT) from T1 to T2. There were also links between levels of anti-spike-RBD-IgG and T cell at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Interpretation: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. Funding: Deutsche Forschungsgemeinschaft (DFG), ER723/3-1

scholarly journals CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

2021 ◽  
Author(s):  
Yiru Long ◽  
Jianhua Sun ◽  
Tingting Liu ◽  
Feng Tang ◽  
Xinxin Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Herd Immunity ◽  
Peptide Vaccine ◽  
Cell Responses ◽  
High Efficient ◽  
T Cell Immune Responses ◽  
Cellular Immune

AbstractSafe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+ T cell responses and Th1-biased CD4+ T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro.One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods

2021 ◽  
Vol 21 ◽  
Author(s):  
Faroogh Marofi ◽  
Ramyar Azizi ◽  
Roza Motavalli ◽  
Ghasem Vahedi ◽  
Maryam Nasimi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Skin Color ◽  
Color Change ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Diagnostic Techniques ◽  
Diagnostic Methods ◽  
World Health ◽  
Therapeutic Approaches

: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via angiotensin-converting enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to the human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the acute respiratory distress syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people with the help of sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

scholarly journals Activation or exhaustion of CD8+ T cells in patients with COVID-19

2021 ◽  
Author(s):  
Min-Seok Rha ◽  
Eui-Cheol Shin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Absolute Number ◽  
T Cell Memory ◽  
Checkpoint Receptors ◽  
Functional Analyses ◽  
Inhibitory Immune Checkpoint

AbstractIn addition to CD4+ T cells and neutralizing antibodies, CD8+ T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8+ T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8+ T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8+ T cells from patients with COVID-19. However, whether CD8+ T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8+ T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8+ T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8+ T cells and discuss long-term SARS-CoV-2-specific CD8+ T-cell memory.

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