Study shows that older adults can generate robust, long-lived memory against SARS-CoV-2 following infection

In a recent study published in The Lancet Health Longevity, researchers reported on the benefit of immunity developed by previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for overcoming the age-associated decline in coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE).

Study: Natural immunity helps overcome the age-related decline of SARS-CoV-2 vaccine immunogenicity. Image Credit: Perfect Wave/Shutterstock
Study: Natural immunity helps overcome the age-related decline of SARS-CoV-2 vaccine immunogenicity. Image Credit: Perfect Wave/Shutterstock

Background

COVID-19 vaccines have been developed to prevent SARS-CoV-2 infections; however, natural immunity gained by previous SARS-CoV-2 infections is especially beneficial for older individuals in whom the efficacy of COVID-19 vaccines is low. Previous studies have supported the notion, as greater antibody titers have been observed among individuals with prior COVID-19 history compared to COVID-19 vaccine recipients without prior COVID-19 history.

It has been found that VE of COVID-19 vaccines against SARS-CoV-2 infections post-second vaccine dose among adults without prior COVID-19 reduces from 85% (post-30 days to 60 days) to 51% after about nine months. On the other hand, VE remains at 90% even after nine months among those with prior COVID-19. In addition, previous SARS-CoV-2 exposure has been found to protect against COVID-19 severity, indicating higher adaptive immune responses involving a cluster of differentiation 8 (CD8) cytotoxic and CD4 helper T-lymphocytes.

About the study

In the present study, researchers highlighted the benefits of previous SARS-CoV-2 infection among older adults with reduced VE of COVID-19 vaccines.

The study comprised about 500 staff members <65 years and residents >65 years old (of whom 80% were aged above 80 years). The study cohort received the second dose of either the BNT162b2 (BioNTech–Pfizer) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines and the titers of antibodies against the SARS-CoV-2 spike (S) protein post second COVID-19 vaccination were assessed. In addition, the effect of the second COVID-19 vaccination on SARS-CoV-2 neutralization was evaluated.

To evaluate the cell-mediated (T lymphocyte) immune responses, peripheral blood mononuclear cells (PMBCs) that produced interferon-gamma (IFN-γ) were quantified. Further, the expression of cytokines such as tumor necrosis factor (TNF) and chemokines such as C-X-C motif chemokine ligand 10 (CXCL10) was evaluated among the two groups. Subsequently, the cytokines were stained intracellularly to particularly quantify IFN-γ- and interleukin 2 (IL-2)-producing CD4 T lymphocytes.

Results

The second vaccination with either BNT162b2 or ChAdOx1 nCoV-19 vaccines significantly boosted anti-S titers and enhanced the neutralization of SARS-CoV-2. The effects were substantially higher among staff than residents. However, the findings were true only for the study participants with no prior COVID-19 history; previously seropositive residents [with antibody titers against the SARS-CoV-2 nucleocapsid (N) protein] demonstrated similar titers as the staff group. Importantly, both groups demonstrated almost 100% SARS-CoV-2 neutralization.

T lymphocyte or cell-mediated immune responses were similar to their humoral or antibody-mediated counterparts, although prior COVID-19 history provided less beneficial effects on the immunity of the staff group individuals. Prior COVID-19 history was associated with substantially higher expression of TNF and CXCL10 after stimulation with S protein ex vivo.

Differences in frequencies of IFN-γ- and IL-2-producing CD4 lymphocytes were not substantially apparent based on the status of SARS-CoV-2 infections; however, the central memory CD4 T lymphocyte frequency was double in individuals with prior COVID-19 history. On the contrary, T lymphocytes that featured a phenotype with terminal differentiation were lower by four-fold among those with prior COVID-19 history compared to those without prior COVID-19 history.

Conclusions

Overall, the study findings showed that elder and frail adult individuals could generate robust and long-term memory anti-SARS-CoV-2 responses following COVID-19, comparable to younger adult individuals. The present study adds knowledge essential to understanding age-related differences in the immunological system.

In addition, the study findings provide potential clues to mechanisms by which natural immunity developed due to previous SARS-CoV-2 infection could support COVID-19 vaccine responses. The study results indicate a potential role of central memory CD4 T lymphocytes and IFN-γ-releasing memory CD8 T lymphocytes in the immune benefits of previous SARS-CoV-2 infection. The CD4 and CD8 lymphocytes could support mucosal defense against SARS-CoV-2 infections by the activation of cells of innate immunity while causing chemokine-mediated stimulation of effectors.

The study findings could inform policymakers to identify individuals at the high priority of preventive measures against COVID-19. However, further research must be conducted to evaluate the extent to which natural SARS-CoV-2 infections provide immune protection against future SARS-CoV-2 variants in older adults and elucidate the mechanisms of such immune protection.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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