A team of scientists from Canada and Spain recently evaluated the durability of antigen-specific immune responses in coronavirus disease 2019 (COVID-19) recovered individuals. They have also identified potential host factors associated with robust and long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity.

The study –conducted by researchers at the University of Alberta and the Gregorio Marañón University General Hospital – is currently available on the bioRxiv* preprint server.

Background

The intensity and persistence of COVID-19 symptoms primarily depend on the robustness of host immune responses. To protect the global population from COVID-19, it is vital to develop anti-SARS-CoV-2 immunity via natural infection or vaccination. However, in COVID-19 recovered individuals, a sharp decline in humoral immunity has been observed after 6 – 8 months of symptom onset. The short durability of anti-SARS-CoV-2 immunity is the primary cause of viral reinfection and COVID-19 recurrence.

Regarding cell-mediated immunity, studies have shown that a robust T cell-specific immune response is vital for SARS-CoV-2 clearance and long-lasting immunity development. In the case of SARS-CoV infection – a betacoronavirus in the same subgenus as SARS-CoV-2 – the presence of memory T cells has been observed in sera even after 11 years post-infection.

In the current study, the scientists have examined the durability of anti-SARS-CoV-2 immune responses in COVID-19 recovered individuals. They have also investigated the host factors that may modulate the strength and durability of anti-COVID-19 immunity.

Study design

The scientists collected blood samples from 35 COVID-19 recovered individuals 12 – 305 days after infection onset. Among participants, 29 had mild symptoms, 2 had moderate symptoms, and 4 were asymptomatic. About 94% of participants did not require hospitalization due to COVID-19, whereas 6% were hospitalized with moderate symptoms.   

Peripheral blood mononuclear cells isolated from the participants were stimulated with SARS-CoV-2-derived spike, nucleocapsid, and membrane proteins (peptide pool) to determine memory T cell response and spike-specific antibodies in plasma.

Important observations

By estimating cytokine expression levels in peripheral blood mononuclear cells, the scientists observed significantly higher frequencies of IFN-γ- and TNF-α-producing CD4+ T-cells in peptide pool-stimulated cells compared to that in non-stimulated cells. These observations indicate the presence of SARS-CoV-2-specific T cells in COVID-19 recovered individuals. However, no induction of IL-17A- and IL-4-producing CD4+ or CD8+ T-cells was observed in response to SARS-CoV-2-derived peptide pool.

With further analysis, the scientists detected that viral membrane protein induced the strongest CD4+ memory T cell response, followed by spike protein and nucleocapsid protein. The induction of CD4+ memory T cell immunity in response to the viral peptide pool was observed in almost all participants.

By analyzing the duration between onset and clearance of infection, the scientists observed that recovery from viral infection occurred in participants between 6 and 30 days after viral detection. They also observed a positive correlation between the duration of active infection and TNF-α specific T cell response to membrane and nucleocapsid proteins. A similar correlation was observed for plasma levels of IgG-specific anti-S1 and anti-receptor binding domain (RBD) antibodies.

By examining immune responses after 10 months of infection, the scientists observed that the levels of anti-RBD antibodies decreased significantly over time. By analyzing T cell-specific immune responses in participants, they observed that the frequency of individuals with TNF-α/CD4+ T-cell response to spike and nucleocapsid proteins reduced significantly over time. Meanwhile, the T cell response to membrane protein remained unchanged.

Factors associated with clinical outcomes

By analyzing various host factors associated with SARS-CoV-2 infection susceptibility, the scientists established a positive correlation between age and time required for viral clearance. Moreover, they observed that participants with A+ blood group required significantly higher time (23 days) for viral clearance than those with O+ blood group (13 days).

Furthermore, they observed significantly higher levels of IgG-specific anti-A antibodies in asymptomatic participants compared to that in mildly symptomatic participants. Similarly, among participants with O+ blood group, they observed significantly higher levels of IgG-specific anti-B antibodies in participants with a low viral load than those with a high viral load.

With further analysis, they observed that the incidence of lymphopenia (low lymphocyte count) was more frequent in participants with the A-blood group. Importantly, they observed that although initially presented with robust cellular and humoral immunity, participants with the A-blood group showed a gradual reduction in immune response over time. In contrast, participants with the O-blood group showed exactly the opposite trend with long-lasting immunity against COVID-19.

Study significance

The study findings confirm the presence of SARS-CoV-2 specific T cell, and antibody responses in COVID-19 recovered individuals after 10 months of infection. Moreover, the study highlights the importance of the ABO blood group system in shaping humoral and cellular immunity against COVID-19.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.