Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals

Therapeutic InfectiologyVirology
Robbiani DF et al

Main result

Between April 1 and May 8, 2020, 157 eligible participants enrolled in the study. Of these, 111 (70.7%) were individuals diagnosed with SARS-CoV-2 infection by RT-PCR (cases), and 46 (29.3%) were close contacts of individuals diagnosed with SARS-CoV-2 infection (contacts). . While inclusion criteria allowed for enrollment of asymptomatic participants, 8 contacts that did not develop symptoms were excluded from further analyses. The 149 cases and contacts were free of symptoms suggestive of COVID-19 for at least 14 days at the time of sample collection. Only one individual who tested positive for SARS-CoV-2 infection by RT-PCR remained asymptomatic. The other 148 participants reported symptoms suggestive of COVID-19 with an average onset of approximately 39 days (range 17 to 67 days) before sample collection.

Plasma samples were tested for binding to the SARS-CoV-2 RBD and trimeric spike (S) proteins by a validated ELISA using anti-IgG or -IgM secondary antibodies for detection. Overall, 78% and 70% of the plasma samples tested showed anti-RBD and anti-S IgG AUCs that were at least 2 standard deviations above the control. In contrast, only 15% and 34% of the plasma samples showed IgM responses to anti-RBD and anti-S that were at least 2 standard deviations above control, respectively.

The overall level of neutralizing activity in the cohort, as measured by the half-maximal neutralizing titer (NT50) was generally low, with 33% less than 50 and 79% below 1,000, while only 2 individuals reached NT50s above 5,000.

Antibody sequencing revealed enlarged clones of RBD-specific memory B cells expressing closely related antibodies in different individuals.

To determine whether the monoclonal antibodies have neutralizing activity, they were tested against the SARS-CoV-2 pseudovirus. Among 89 RBD binding antibodies tested, 52 were found to neutralize SARS-CoV-2 pseudovirus with nanogram per milliliter half-maximal inhibitory concentrations (IC50s) ranging from 3 to 709. A subset of the most potent of these antibodies were also tested against authentic SARS-CoV-2 and neutralized with IC50s of less than 5 ng/ml. Only two of the antibodies which cross-reacted with the RBD of SARS-CoV showed significant neutralizing activity against SARS-CoV pseudovirus.


Most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specifc antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Strength of evidence Weak

- Monocentric cohort study
- N=149


To study antibodies against SARS-CoV-2 in 149 patients recovering from COVID-19.


Study participants were recruited at the Rockefeller University Hospital in New York from April 1 through May 8, 2020. . Eligible participants were adults aged 18-76 years who were either diagnosed with SARS-CoV-2 infection by RT-PCR and were free of symptoms of COVID-19 for at least 14 days (cases), or who were close contacts with someone who had been diagnosed with SARS-CoV-2 infection by RT-PCR and were free of symptoms suggestive of COVID-19 for at least 14 days (contacts). Exclusion criteria included presence of symptoms suggestive of active SARS-CoV-2 infection, or hemoglobin < 12 g/dL for males and < 11 g/dL for females.

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