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Durable SARS-CoV-2 B cell immunity after mild or severe disease.

ABSTRACT: Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.

SUBMITTER: Ogega CO

PROVIDER: S-EPMC7605583 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Durable SARS-CoV-2 B cell immunity after mild or severe disease.

Ogega Clinton O CO Skinner Nicole E NE Blair Paul W PW Park Han-Sol HS Littlefield Kirsten K Ganesan Abhinaya A Ladiwala Pranay P Antar Annukka Ar AA Ray Stuart C SC Betenbaugh Michael J MJ Pekosz Andrew A Klein Sabra L SL Manabe Yukari C YC Cox Andrea L AL Bailey Justin R JR

medRxiv : the preprint server for health sciences 20201030

Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-speci ...[more]

PMID: 33140070

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Project description:IntroductionThe coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency causing a disparate burden of death and disability around the world. The viral genetic variants associated with outcome severity are still being discovered.MethodsWe downloaded 155 958 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from GISAID. Of these genomes, 3637 samples included useable metadata on patient outcomes. Using this subset, we evaluated whether SARS-CoV-2 viral genomic variants improved prediction of reported severity beyond age and region. First, we established whether including genomic variants as model features meaningfully increased the predictive power of our model. Next, we evaluated specific variants in order to determine the magnitude of association with severity and the frequency of these variants among SARS-CoV-2 genomes.ResultsLogistic regression models that included viral genomic variants outperformed other models (area under the curve = 0.91 as compared with 0.68 for age and gender alone; P < 0.001). We found 84 variants with odds ratios greater than 2 for outcome severity (17 and 67 for higher and lower severity, respectively). The median frequency of associated variants was 0.15% (interquartile range 0.09-0.45%). Altogether 85% of genomes had at least one variant associated with patient outcome.ConclusionNumerous SARS-CoV-2 variants have 2-fold or greater association with odds of mild or severe outcome and collectively, these variants are common. In addition to comprehensive mitigation efforts, public health measures should be prioritized to control the more severe manifestations of COVID-19 and the transmission chains linked to these severe cases.Lay summary: This study explores which, if any, SARS-CoV-2 viral genomic variants are associated with mild or severe COVID-19 patient outcomes. Our results suggest that there are common genomic variants in SARS-CoV-2 that are more often associated with negative patient outcomes, which may impact downstream public health measures.

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Durable SARS-CoV-2 B cell immunity after mild or severe disease.

Publications

Durable SARS-CoV-2 B cell immunity after mild or severe disease.

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