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1.
Emerg Infect Dis ; 27(9): 2454-2458, 2021 09.
Article in English | MEDLINE | ID: covidwho-1435936

ABSTRACT

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.


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

ABSTRACT

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.


Subject(s)
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
3.
iScience ; 24(3): 102254, 2021 Mar 19.
Article in English | MEDLINE | ID: covidwho-1122297

ABSTRACT

Epidemiological data showing increased severity and mortality of COVID-19 in men suggests a potential role for androgen in SARS-CoV-2 infection. Here, we present evidence for the transcriptional regulation of SARS-CoV-2 host cell receptor ACE2 and TMPRSS2 by androgen in mouse and human cells. Additionally, we demonstrate the endogenous interaction between TMPRSS2 and ACE2 in human cells and validate ACE2 as a TMPRSS2 substrate. Furthermore, camostat-a TMPRSS2 inhibitor-blocked the cleavage of pseudotype SARS-CoV-2 surface Spike without disrupting TMPRSS2-ACE2 interaction, thus providing evidence for the first time of a direct role of TMPRSS2 in priming the SARS-CoV-2 Spike, required for viral fusion to the host cell. Importantly, androgen-deprivation, anti-androgens, or camostat attenuated the SARS-CoV-2 S-mediated cellular entry. Together, our data provide a strong rationale for clinical evaluations of TMPRSS2 inhibitors and androgen-deprivation therapy/androgen receptor antagonists alone or in combination with antiviral drugs as early as clinically possible to prevent COVID-19 progression.

4.
Cell Rep Med ; 2(1): 100164, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-957488

ABSTRACT

Convalescent plasma (CP) is widely used to treat COVID-19, but without formal evidence of efficacy. Here, we report the beneficial effects of CP in a severely ill COVID-19 patient with prolonged pneumonia and advanced chronic lymphocytic leukemia (CLL), who was unable to generate an antiviral antibody response of her own. On day 33 after becoming symptomatic, the patient received CP containing high-titer (ID50 > 5,000) neutralizing antibodies (NAbs), defervesced, and improved clinically within 48 h and was discharged on day 37. Hence, when present in sufficient quantities, NAbs to SARS-CoV-2 have clinical benefit even if administered relatively late in the disease course. However, analysis of additional CP units revealed widely varying NAb titers, with many recipients exhibiting endogenous NAb responses far exceeding those of the administered units. To obtain the full therapeutic benefits of CP immunotherapy, it will thus be important to determine the neutralizing activity in both CP units and transfusion candidates.


Subject(s)
COVID-19/therapy , Aged , Antibodies, Neutralizing/administration & dosage , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Female , Humans , Immunization, Passive , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lung/diagnostic imaging , SARS-CoV-2/isolation & purification , Severity of Illness Index , Tomography, X-Ray Computed
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