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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311276

ABSTRACT

Purpose: COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay . ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311275

ABSTRACT

Early detection of infections is crucial to limit the spread of coronavirus 2019 disease (COVID-19). Here, we developed a flow cytometry-based assay to detect SARS-CoV-2 Spike protein (S protein) antibodies in COVID-19 patients. The assay detected specific IgM and IgG in COVID-19 patients and also the acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response was significantly higher at a later stage of the infection. Furthermore, asymptomatic COVID-19 patients also developed specific IgM and IgG, with IgG1 as the most dominant subclass. Although the antibody levels were lower in asymptomatic infections, the assay was highly sensitive and detected 97% of asymptomatic infections. These findings demonstrated that the assay could be used for serological analysis of symptomatic patients, and also as a sensitive tool to detect asymptomatic infections, which may go undetected.Funding: Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001, COVID-19RF-007, COVID-19RF-60).Conflict of Interest: The authors declare no competing interests.Ethical Approval: The study design and protocols for COVID-19, recovered SARS and seasonal human CoV patient cohorts were approved by National Healthcare Group (NHG) Domain Specific Review Board (DSRB) and performed, following ethical guidelines in the approved studies 2012/00917, 2020/00091 and 2020/00076 respectively. Healthy donor samples were collected in accordance with approved studies 2017/2806 and NUS IRB 04-140. Written informed consent was obtained from participants in accordance with the Declaration of Helsinki for Human Research.

4.
EMBO Mol Med ; 14(3): e15227, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1643965

ABSTRACT

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1ß and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.


Subject(s)
COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296939

ABSTRACT

Efficient COVID-19 vaccines have been developed in record time. Here, we present findings from a comprehensive and integrated analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 mRNA vaccine. Two vaccine doses induced high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of delta variant was less efficient than that of the Wuhan strain. Age stratified analyses identified a group of low antibody responders where individuals ≥ 60 years were overrepresented. Waning of the antibody and cellular responses was observed in 30% of the vaccinees after six months. However, age did not influence the waning of these responses. Taken together, while individuals ≥ 60 years old took longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at six months post-vaccination. However, the higher proportion of older individuals in the group of antibody low responders and the lower antibody reactivity the Delta variant call for a booster immunization to increase immune responses and protection.

6.
Front Immunol ; 12: 710217, 2021.
Article in English | MEDLINE | ID: covidwho-1555700

ABSTRACT

Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/complications , Cohort Studies , Convalescence , Female , Humans , Male , Middle Aged
7.
J Clin Immunol ; 42(2): 214-229, 2022 02.
Article in English | MEDLINE | ID: covidwho-1544509

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Cytokines/immunology , Host-Pathogen Interactions/immunology , Humans , Inflammation/immunology , Mutation/immunology , Pandemics/prevention & control , T-Lymphocytes/immunology
9.
ACS Nano ; 2021 Jun 16.
Article in English | MEDLINE | ID: covidwho-1270651

ABSTRACT

Rapid and inexpensive immunodiagnostic assays to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroconversion are essential for conducting large-scale COVID-19 epidemiological surveillance and profiling humoral responses against SARS-CoV-2 infections or immunizations. Herein, a colorimetic serological assay to detect SARS-CoV-2 IgGs in patients' plasma was developed using short antigenic epitopes conjugated to gold nanoparticles (AuNPs). Four immunodominant linear B-cell epitopes, located on the spike (S) and nucleocapsid (N) proteins of SARS-CoV-2, were characterized for their IgG binding affinity and used as highly specific biological motifs on the nanoparticle to recognize target antibodies. Specific bivalent binding between SARS-CoV-2 antibodies and epitope-functionalized AuNPs trigger nanoparticle aggregation, which manifests as a distinct optical transition in the AuNPs' plasmon characteristics within 30 min of antibody introduction. Co-immobilization of two epitopes improved the assay sensitivity relative to single-epitope AuNPs with a limit of detection of 3.2 nM, commensurate with IgG levels in convalescent COVID-19-infected patients. A passivation strategy was further pursued to preserve the sensing response in human plasma medium. When tested against 35 clinical plasma samples of varying illness severity, the optimized nanosensor assay can successfully identify SARS-CoV-2 infection with 100% specificity and 83% sensitivity. As the epitopes are conserved within the circulating COVID-19 variants, the proposed platform holds great potential to serve as a cost-effective and highly specific alternative to classical immunoassays employing recombinant viral proteins. These epitope-enabled nanosensors further expand the serodiagnostic toolbox for COVID-19 epidemiological study, humoral response monitoring, or vaccine efficiency assessment.

10.
Open Forum Infect Dis ; 8(6): ofab156, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1258788

ABSTRACT

BACKGROUND: The complications and sequelae of coronavirus disease 2019 (COVID-19) and their effect on long-term health are unclear, and the trajectory of associated immune dysregulation is poorly understood. METHODS: We conducted a prospective longitudinal multicenter cohort study at 4 public hospitals in Singapore. Patients with COVID-19 were monitored for a median of 6 months after recovery from acute infection. Clinical symptoms and radiologic data were collected, along with plasma samples for quantification of immune mediators. The relationship between clinical symptoms and immune cytokine profiles was investigated. RESULTS: Two hundred eighty-eight participants were recruited, and follow-up data were available for 183, 175, and 120 participants at days 30, 90, and 180 postsymptom onset, respectively. Symptoms related to COVID-19 were present in 31 (16.9%), 13 (7.4%), and 14 (11.7%) at days 30, 90, and 180. In a multivariable model, age >65 years, non-Chinese ethnicity, and the severity of acute infection were associated with increased likelihood of persistent symptoms. Recovered COVID-19 patients had elevated levels of proinflammatory interleukin (IL)-17A, stem cell factor, IL-12p70, and IL-1ß and pro-angiogenic macrophage inflammatory protein 1ß, brain-derived neurotrophic factor, and vascular endothelial growth factor at day 180 compared with healthy controls. Higher levels of monocyte chemoattractant protein-1 and platelet-derived growth factor-BB were detected in patients with persistent symptoms, versus symptom-free patients. CONCLUSIONS: Approximately 10% of recovered patients had persistent symptoms 6 months after initial infection. Immune cytokine signatures of the recovered patients reflected ongoing chronic inflammation and angiogenesis. Patients with COVID-19 should be monitored closely for emerging long-term health consequences.

11.
EMBO Mol Med ; 13(6): e14045, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1219070

ABSTRACT

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.


Subject(s)
COVID-19/pathology , Carrier State/immunology , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/metabolism , COVID-19/immunology , COVID-19/virology , Carrier State/pathology , Carrier State/virology , Cytokines/metabolism , Humans , Monocytes/cytology , Monocytes/immunology , Monocytes/metabolism , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Th17 Cells/cytology , Th17 Cells/immunology , Th17 Cells/metabolism , Transcriptome , Up-Regulation , Vascular Endothelial Growth Factor D/metabolism
12.
Clin Transl Immunology ; 10(2): e1241, 2021.
Article in English | MEDLINE | ID: covidwho-1095258

ABSTRACT

OBJECTIVES: The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralise against the G614 variant. METHODS: Antibody profiling against the SARS-CoV-2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS-CoV-2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID-19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). RESULTS: Profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. CONCLUSIONS: Cross-reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS-CoV-2. More importantly, there should be negligible impact towards the efficacy of antibody-based therapies and vaccines that are currently being developed.

13.
Cell Rep Med ; 2(2): 100193, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1069040

ABSTRACT

Early detection of infection is crucial to limit the spread of coronavirus disease 2019 (COVID-19). Here we develop a flow cytometry-based assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antibodies in individuals with COVID-19. The assay detects specific immunoglobulin M (IgM), IgA, and IgG in individuals with COVID-19 and also acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of infection. Furthermore, asymptomatic individuals with COVID-19 also develop specific IgM, IgA, and IgG, with IgG1 being the most dominant subclass. Although the antibody levels are lower in asymptomatic infection, the assay is highly sensitive and detects 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic and asymptomatic infections, which may otherwise remain undetected.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Immunoglobulin Class Switching/physiology , Immunoglobulin G/blood , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Asymptomatic Diseases , COVID-19/immunology , COVID-19/virology , Flow Cytometry , Humans , Immunoglobulin G/immunology , Immunologic Tests/methods , SARS-CoV-2/isolation & purification
15.
Nat Commun ; 11(1): 5243, 2020 10 16.
Article in English | MEDLINE | ID: covidwho-872700

ABSTRACT

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.


Subject(s)
Betacoronavirus/immunology , CD8-Positive T-Lymphocytes/immunology , Neutrophils/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Biomarkers/blood , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Flow Cytometry , Humans , Immunophenotyping/methods , Interleukin-10/blood , Interleukin-6/blood , Lymphocyte Count , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2 , Severity of Illness Index
16.
Lancet ; 396(10251): 603-611, 2020 08 29.
Article in English | MEDLINE | ID: covidwho-719049

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. METHODS: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. FINDINGS: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only. INTERPRETATION: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. FUNDING: National Medical Research Council Singapore.


Subject(s)
Coronavirus Infections/virology , Gene Deletion , Genome, Viral/genetics , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Humans , Hypoxia/etiology , Hypoxia/therapy , Middle Aged , Open Reading Frames , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Prospective Studies , Respiratory Therapy , SARS-CoV-2 , Severity of Illness Index , Singapore/epidemiology , Virus Replication
17.
EBioMedicine ; 58: 102911, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-662643

ABSTRACT

BACKGROUND: Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS: Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. FINDINGS: Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. INTERPRETATION: IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs). FUNDING: Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001) and CCGSFPOR20002. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR.


Subject(s)
B-Lymphocytes/immunology , Coronavirus Infections/diagnosis , Epitopes/immunology , Nucleocapsid Proteins/immunology , Pneumonia, Viral/diagnosis , Spike Glycoprotein, Coronavirus/immunology , Adult , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Epitopes/blood , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Serologic Tests/methods
18.
Nat Commun ; 11(1): 2806, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-459009

ABSTRACT

Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , Coronavirus Infections/blood , Epitopes, B-Lymphocyte , Humans , Immunodominant Epitopes , Immunoglobulin G/blood , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
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