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Emerg Infect Dis ; 27(9): 2454-2458, 2021 09.
Article in English | MEDLINE | ID: covidwho-1435936


Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2-specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.

COVID-19 , Antibody Formation , COVID-19/immunology , COVID-19 Serological Testing , Humans , Nasopharynx , SARS-CoV-2 , Seroconversion
PLoS Pathog ; 17(7): e1009761, 2021 07.
Article in English | MEDLINE | ID: covidwho-1315898


T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.

Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , T Follicular Helper Cells/immunology , T Follicular Helper Cells/virology , Adult , Aged , Antibody Specificity , Case-Control Studies , Coronavirus Nucleocapsid Proteins/immunology , Female , Host Microbial Interactions/immunology , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Viral Matrix Proteins/immunology , Young Adult