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1.
Lancet Microbe ; 3(3): e173-e183, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1758019

ABSTRACT

Background: We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein. Methods: Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19-49 years for the GX-19 trial and healthy adults aged 19-54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov. Findings: Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1·5 mg group and 20 [50%] in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p<0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group). Interpretation: GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity. Funding: The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.

2.
J Med Virol ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1718373

ABSTRACT

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327580

ABSTRACT

Natural infection with SARS-CoV-2 or vaccination induces virus-specific immunity protecting hosts from infection and severe disease. While the infection-preventing immunity gradually declines, the severity-reducing immunity is relatively well preserved. Here, based on the different longevity of these distinct immunities, we develop a mathematical model to estimate courses of endemic transition of COVID-19. Our analysis demonstrates that high viral transmission unexpectedly reduces the rates of progression to severe COVID-19 during the course of endemic transition despite increased numbers of infection cases. Our study also shows that high viral transmission amongst populations with high vaccination coverages paradoxically accelerates the endemic transition of COVID-19 with reduced numbers of severe cases. These results provide critical insights for driving public health policies in the era of ‘living with COVID-19’.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320007

ABSTRACT

Memory T-cell responses have been demonstrated after recovery from SARS-CoV-2 infection, but the phenotypes of SARS-CoV-2-specific T cells have not been comprehensively investigated ex vivo. We detected SARS-CoV-2-specific CD8+ T cells by MHC-I multimer staining and examined their phenotypes in relation to their functional capacity in acute and convalescent COVID-19. In the convalescent phase, multimer+ cells exhibited early differentiated effector-memory phenotypes. The frequency of CD127+KLRG1- memory precursor effector cells among multimer+ cells was significantly lower in convalescent individuals with severe disease than those with mild disease. Cytokine-secretion assays combined with MHC-I multimer staining revealed that the proportion of IFN-γ-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to other viruses. Importantly, the proportion of IFN-γ-producing cells was significantly higher in PD-1+ cells than PD-1- cells among multimer+ cells in both the acute and convalescence phases, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our findings provide insights for effective vaccine development.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318062

ABSTRACT

Background: There is insufficient data on the longevity of immunity acquired following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19).Methods: Convalescent blood was collected prospectively from 97 patients who had recovered from COVID-19. The level of humoral immunity to SARS-CoV-2 was measured using the anti-SARS-CoV-2 nucleocapsid immunoglobulin G (IgG) assay and the plaque reduction neutralization test with sera collected at three periods: within 8 weeks, at 9-20 weeks, and at 22-27 weeks after diagnosis. IFN-γ ELISpot assays were conducted using overlapping peptides covering spike, nucleocapsid, and membrane proteins of SARS-CoV-2.Findings: The study population comprised asymptomatic (n=14), symptomatic/non-pneumonic (n=42), and pneumonic (n=41) patients. The anti-SARS-CoV-2 IgG and neutralizing antibody (NAb) titers lasted until six months after diagnosis, with positivity rates of 66·7% and 86·9%, respectively. The level of humoral immunity at six months after diagnosis were significantly higher in the pneumonic group than in the symptomatic/non-pneumonic group. Older age, prolonged viral shedding and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. SARS-CoV-2 specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity.Interpretation: Most (> 85%) patients carries NAb until six months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19.Funding Statement: This study was supported by a grant of the Korea National Institute of Health, Korea Disease Control and Prevention Agency (project number: 2020-ER5314-00), Korea University Guro Hospital (Korea research-driven hospital) (No. O2001061), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI20C0452).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of the Korea University Guro Hospital (approval number: 2020GR0130). All participants provided written informed consent.

7.
Mol Cells ; 44(6): 401-407, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1687545

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4+ and CD8+ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.


Subject(s)
Antibodies, Neutralizing/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/pathogenicity , Antibodies, Viral/biosynthesis , CD4-Positive T-Lymphocytes/classification , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/classification , CD8-Positive T-Lymphocytes/virology , COVID-19/pathology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Convalescence , Cytokines/biosynthesis , Cytotoxicity, Immunologic , Host-Pathogen Interactions/immunology , Humans , Immunity, Humoral , Immunologic Memory , Immunophenotyping , SARS-CoV-2/immunology , Severity of Illness Index
9.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294047

ABSTRACT

Background We investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein. Methods Two open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19–55 years. GX-19 trial participants received two vaccine injections (1·5 mg or 3·0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3·0 mg vaccine injections four weeks apart. Findings Between June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52·5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1·5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85·74, 144·20, and 201·59 in the 1·5 mg, 3·0 mg GX-19 groups and the 3·0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variants Interpretation GX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants. Funding This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea). Research in context Evidence before this study To overcome the COVID-19 outbreak, the development of safe and effective vaccines is crucial. Despite the successful clinical efficacy of the approved vaccines, concerns exist regarding emerging new SARS-CoV-2 variants that have mutated receptor binding domains in the spike protein. We searched PubMed for research articles published up to May 1, 2021, using various combinations of the terms “COVID-19” or “SARS-CoV-2”, “vaccine”, and “clinical trial”. No language or data restrictions were applied. We also searched the ClinicalTrials.gov registry and World Health Organization (WHO) draft landscape of COVID-19 candidate vaccines for ongoing trials of COVID-19 vaccines up to May 1, 2021. Ten DNA-based vaccines, including the vaccine candidate reported here, are in ongoing clinical trials. Among these, safety and immunogenicity results were reported from only one phase 1 trial of a DNA vaccine against SARS-CoV-2 (INO-4800). INO-4800 demonstrated favorable safety and tolerability and was immunogenic, eliciting humoral and/or cellular immune responses in all vaccinated subjects. There is only one ongoing clinical trial of a vaccine against SARS-CoV-2 variants (mRNA-1273.351). Added value of this study This is the first-in-human phase 1 trial in healthy adults of a recombinant DNA vaccine for COVID-19 (GX-19N) containing the coding regions of both the spike and nucleocapsid proteins. This trial showed that GX-19N is safe, tolerated, and able to induce both humoral and cellular responses. A two-dose vaccination of 3·0 mg GX-19N (on days 1 and 29) induced significant humoral a d cellular responses. The neutralizing geometric mean titers in individuals vaccinated with GX-19N were lower than those of human convalescent sera. However, the GX-19N group showed increased T cell responses, which was similar to those analyzed using convalescent PBMCs. Furthermore, GX-19N induced not only SARS-CoV-2 spike-specific T cell responses but also broad nucleocapsid-specific T cell responses, which were also specific to SARS-CoV-2 variants. Implications of all the available evidence It is important to note that GX-19N contains a plasmid encoding both the spike and nucleocapsid proteins, and that it showed broad SARS-CoV-2-specific T cell responses, which may allow cross-reactivity with emerging SARS-CoV-2 variants. Based on these safety and immunogenicity findings, GX-19N was selected for phase 2 immunogenicity trials.

10.
J Med Virol ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1506221

ABSTRACT

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

11.
International Journal of Antimicrobial Agents ; 58:N.PAG-N.PAG, 2021.
Article in English | Academic Search Complete | ID: covidwho-1440062
13.
Signal Transduct Target Ther ; 6(1): 203, 2021 05 22.
Article in English | MEDLINE | ID: covidwho-1387226
15.
J Infect Dis ; 224(5): 754-763, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1381010

ABSTRACT

BACKGROUND: There is insufficient data on the longevity of immunity acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19). The study population comprised asymptomatic (n = 14), symptomatic/nonpneumonic (n = 42), and pneumonic (n = 41) patients. RESULTS: The anti-SARS-CoV-2 immunoglobulin class G and neutralizing antibody (NAb) titers lasted until 6 months after diagnosis, with positivity rates of 66.7% and 86.9%, respectively. Older age, prolonged viral shedding, and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. Severe acute respiratory syndrome coronavirus 2-specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity. CONCLUSIONS: In conclusion, most (>85%) patients carry NAb until 6 months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/virology , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G/immunology , Longitudinal Studies , Male , Middle Aged , Prospective Studies , T-Lymphocytes/immunology , Virus Shedding
16.
Am J Trop Med Hyg ; 105(2): 395-400, 2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1374604

ABSTRACT

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Severity of Illness Index , T-Lymphocytes/immunology , Acute Disease , Adult , Aged , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19/pathology , Convalescence , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Interferon-gamma/analysis , Kinetics , Male , Middle Aged , Prospective Studies
17.
Cell Mol Immunol ; 18(10): 2325-2333, 2021 10.
Article in English | MEDLINE | ID: covidwho-1366812

ABSTRACT

In 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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , Immunologic Memory , Lymphocyte Activation , Lymphocyte Count
18.
J Allergy Clin Immunol ; 148(4): 996-1006.e18, 2021 10.
Article in English | MEDLINE | ID: covidwho-1330917

ABSTRACT

BACKGROUND: Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. OBJECTIVE: We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. METHODS: We performed RNA sequencing and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved PBMCs. RESULTS: In RNA-sequencing analysis, the NK cells exhibited distinctive features compared with healthy donors, with significant enrichment of proinflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg NK-cell population expanded in cryopreserved PBMCs from patients with COVID-19 regardless of disease severity, accompanied by decreased NK-cell cytotoxicity. The NK-cell population was rapidly normalized alongside the disappearance of unconventional CD56dimCD16neg NK cells and the recovery of NK-cell cytotoxicity in patients with mild COVID-19, but this occurred slowly in patients with severe COVID-19. CONCLUSIONS: The current longitudinal study provides a deep understanding of the NK-cell biology in COVID-19.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , Lymphocyte Activation , SARS-CoV-2/immunology , Adult , COVID-19/pathology , Humans , Killer Cells, Natural/pathology , Longitudinal Studies , Male , Middle Aged , Prospective Studies , RNA-Seq
19.
Nat Commun ; 12(1): 4043, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1290767

ABSTRACT

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma/blood , Vaccination
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