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Immunological memory to SARS-CoV-2 assessed for greater than six months after infection

Our take —

This study, which has not been peer reviewed, measures components of immune memory at various time points from COVID-19 symptom onset. Despite a small number of repeated measurements, they provide preliminary data that SARS-CoV-2 infection — assuming that it behaves similarly to other pathogens that induce analogous immune responses — can induce sustained immunity to either prevent or lessen the severity of subsequent infection.

Study design

Cross-sectional; Prospective Cohort

Study population and setting

This preprint used cross-sectional data from 185 individuals and longitudinal data from 38 of those individuals to measure SARS-CoV-2-induced antibodies, memory B cells, memory CD8+ T cells, and memory CD4+ T cells from six to 240 days after COVID-19 symptom onset (median 90.5 days). Participants had a documented history of SARS-CoV-2 infection via PCR, serodiagnostics, or both, and lived mostly in California or New York in the United States. Only 7% of participants were hospitalized with COVID-19, 2% of patients were asymptomatic, their ages ranged from 19-81, and participants were more likely to be female than male (57% vs 43%). The authors measured circulating antibody (IgG and IgA), memory B-cells (including surface immunoglobulin isotype), CD8+ T cells, and CD4+ T cells specific to various components of the SARS-CoV-2 virus via assays that included negative and positive controls for each immune component of interest. They created lines of best fit via linear regression or kinetic models for both cross-sectional and longitudinal data and assessed differential immune memory by gender with ANCOVA to assess trends in immune memory after SARS-CoV-2 infection.

Summary of Main Findings

They found that IgG antibody titers tended to decrease slightly from symptom onset with 90% being seropositive at 6-8 months vs 98% at 1 month, regardless of antigen specificity type, although there was high variability in antibody titers across individuals. Memory B cells increased steadily the further individuals got from COVID-19 symptom onset regardless of the antigen type, plateauing around 150 days, with immunoglobulin isotype switching to predominantly IgG+ memory B cells as time progressed. Memory CD8+ and CD4+ T cells, on the other hand, were detectable in a higher percentage of people at earlier measurements (61% and 94% at one month respectively), after which they decreased marginally to 50% and 89% respectively among the 18 participants with data available after six months from COVID-19 symptom onset. These trends seem to hold in individuals who provided data at more than one time point across all immune components. They further homed in on CD4+ T follicular helper cells — cells essential for activating memory B cells that then produce antibodies in response to an antigen — which were stable among tested individuals for at least six months from symptom onset. Finally, they found no significant differences in immune memory by gender or hospitalization status.

Study Strengths

This study provides an in-depth assessment of both circulating antibodies and memory B- and T-cells following symptom onset of natural COVID-19 infection. A subset of their participants provided data at more than one time point, which allowed for comparisons across time in individuals.

Limitations

It appears that in calculating lines of best fit for various antibodies and immune cells, the authors combined data from participants who only provided data at one time point with those who provided data at more than one time point. This introduces data points that are not independent from one another, which biases the lines of best fit in unforeseen ways. Furthermore, it is difficult to compare antibody or immune cell titers across time in different individuals, since, as the authors note, each person’s immune system reacts to pathogens (such as SARS-CoV-2) differently. The small sample size used also makes it difficult to generalize these data to all individuals infected with SARS-CoV-2. Lastly, it is also unknown how immunological responses to SARS-CoV-2 will differ between those who are naturally infected and individuals who are vaccinated.

Value added

The authors provide evidence, through a rather thorough examination of various immune cell subtypes and responses, for persistent SARS-CoV-2 immunity or reduced disease severity following SARS-CoV-2 infection.

This review was posted on: 20 November 2020