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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312509

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 (ID 50 >5,000) neutralizing antibodies (NAbs), defervesced and improved clinically within 48 hours, and was discharged on day-37. Hence, when present in sufficient quantities, NAbs to SARS-CoV-2 have curative potential even if administered relatively late in the disease course.

2.
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
3.
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
4.
Emerg Infect Dis ; 27(9): 2454-2458, 2021 09.
Article in English | MEDLINE | ID: covidwho-1291007

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
5.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: covidwho-1197299

ABSTRACT

Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.


Subject(s)
Coronavirus Infections/veterinary , Macaca mulatta/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Vaccines, DNA/therapeutic use , Viral Vaccines/therapeutic use , Animals , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Injections, Intradermal , Middle East Respiratory Syndrome Coronavirus/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
6.
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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