Evidence for Functional, Persistent SARS-CoV-2-Specific Immune Memory

Hands of a laboratory worker holding positive test tube for COVID-19 coronavirus
Researchers sought to determine whether individuals recovered from mildly symptomatic COVID-19 develop and sustain immunological memory against the SARS-CoV-2 virus.

In a preprint article posted to Research Square, investigators reported evidence that mild coronavirus disease 2019 (COVID-19) elicits a functional and persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response.

To determine the extent of persistent immune memory induced by cases of mild symptomatic COVID-19, investigators performed a longitudinal assessment of individuals recovered from mildly symptomatic cases. They collected plasma and peripheral blood mononuclear cells from 15 recovered individuals. The median age of recovered individuals was 47 years, and these participants reported mild symptoms lasting a median of 13 days. Participants returned for a second blood draw a median of 86 days after the onset of symptoms.

Researchers compared covered samples with samples collected at 2 time points representing a similar sampling interval in a group of 17 healthy control participants. They also included historical negative plasma samples collected before the first human SARS-CoV-2 infection (2016-2019) as controls.

Investigators reported that recovered individuals developed SARS-CoV-2-specific immunoglobulin (Ig)G antibody and neutralizing plasma, as well as virus-specific memory B (MBC) and T (MTC) cells. These persisted and even increased numerically in some individuals over the 3 months after symptom onset. The SARS-CoV-2-specific memory lymphocytes also exhibited characteristics associated with potent antiviral immunity. The MTCs secreted interferon (IFN) γ and expanded upon reencountering antigen- and MBC-expressed receptors capable of neutralizing virus when expressed as antibodies.

Until a vaccine is available, investigators believe, “natural infection-induced herd immunity could play a key role in reducing infections and deaths.”

In this study, they reported the presence of SARS-CoV-2-specific immune mediators in recovered individuals, including neutralizing antibodies, IgG+T-betlo classical MBCs, circulating cytokine-producing CXCR5+ T follicular helper (Tfh)1 cells, proliferating CXCR3+ cluster of differentiation (CD)4+ memory cells, and IFNγ-producing CD8+ T cells, all of which were maintained to at least 3 months beyond postsymptom onset.

Investigators therefore concluded, “This study predicts that these recovered individuals will be protected from a second SARS-CoV-2 infection and, if so, suggests that Th1 memory should be the target of vaccine elicited memory.”

Investigators acknowledged that additional studies are required in order to understand the variability of responses in a larger cohort and to determine how long the immune memory to SARS-CoV-2 is truly maintained.

Disclosure: Several authors have filed a patent under the provisional serial no. 63/063,841. Please see the original reference for a full list of authors’ disclosures.


Pepper M, Rodda L, Netland J, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. [published online August 13, 2020]. Res Sq. doi:10.21203/rs.3.rs-57112/v1