Immune System Responses

Long-lived Bone Marrow Plasma Cells

In May 2021, "SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans", published in the medical journal Nature, analyzed bone marrow samples to find that people who have recovered from even mild Covid symptoms have robust, antigen-specific immunity in the form of long-lived bone marrow plasma cells (‘BMPC's). Levels of antibodies decrease during the months after infection, as the immune system transitions from "antibody-generating short-lived plasmablasts" to the long-lived BMPCs that are quiescent and “a persistent and essential source of protective antibodies”. “After re-exposure to an antigen, memory B cells rapidly expand and differentiate into antibody-secreting plasmablasts.” This article, by Turner et al. at the Washington University Medical Center, reports the first direct evidence of this immunity mechanism for a viral infection in humans.

In July 2020, "SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls", published in Nature by Le Bert et al. at Duke-NUS Medical School in Singapore, showed that patients "who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that ... displayed robust cross-reactivity to the N protein of SARS-CoV-2", "17 years after the outbreak of SARS in 2003." The article notes that previous work has shown that "SARS-CoV-specific antibodies dropped below the limit of detection within 2-3 years, whereas T cells were detected 11 years after SARS."

In Jan 2021, "Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection" published in Science by Dan et al. at the La Jolla Institute for Immunology, found that for 188 cases of Covid-19 with varying severity from accross the U.S., antibodies against SARS-COV-2 declined moderately and memory B cells increased over 6-8 months. The spike IgA antibody was still present in "the large majority of subjects" at 6 to 8 months. CD4+ T Cell memory was detected in 93% of the subjects at 1 month after infection, and in 92% at 6-8 months. Subjects, 80 male and 108 female, ranged from 19 to 81 years old. Consistent with the general distribution of symptomatic disease severity in the U.S., most of the subjects had a "mild" case of Covid-19, 3% were asymptomatic and 7% were hospitalized, some of whom required ICU care. The results show that "simple serological tests for SARS-CoV-2 antibodies do not reflect the durability of immune memory to SARS-CoV-2."

In April 2021, corroborating results for ~250 convalescents in Atlanta and Seattle were reported in "Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection..." by Cohen et al. This paper also notes that the "spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells."

Further corroborating results for ~75 convalescents with varying disease severity in China are reported in "One-year sustained cellular and humoral immunities of COVID-19 convalescents", published in Clinical Infectious Diseases (Oct 2021) by Zhang et al. at the China CDC. They found SARS-CoV-2-specific IgG antibodies in 95% of the convalescents at 6 and 12 months, but with lower levels at 12 months. SARS-CoV-2-specific T-cell responses to at least one of the virus antigen (S1, S2, M and N) proteins were found in 93% of convalescents at 6 months and in 92% at 12 months. T-cell responses to SARS-CoV-2 were also found in 36% of 28 healthy controls included in the study, indicating possible cross reactivity to common cold coronaviruses in the population. T-cell responses in asymptomatic cases were lower than in the convalescents that had mild, moderate or severe symptoms. T-cell memory against the S protein was correlated with antibody responses at 12 months.

In the Aug 2021 study, "Large-scale study of antibody titer decay..." by a team at the Leumit Research Institute in Israel, antibody titers were measured for 2,653 fully vaccinated individuals who had no history of Covid-19 infection, and for 4,361 SARS-CoV-2 convalescents who did not receive the vaccine. Initially the fully vaccinated had higher SARS-CoV-2 IgG antibody levels, but their levels decreased by up to 40% each subsequent month, while the naturally immune decreased by less than 5% per month. After 6 months, 16% of the fully vaccinated had antibody levels below the threshold for seropositivity, whereas 9 months after infection 11% of the naturally immune were below threshold. Note that, per the April 2021 study above, long-lived BMPCs are generated during the slow decline in antibodies after Covid recovery.