The Immune Responses and Immunity to SARS-CoV-2

Immune responses to SARS-CoV-2 involve both the cell-mediated immunity and antibody production and the European Centre for Disease Prevention and Control discussed the following.

Cell-Mediated Immune Response

T-cell responses against the SARS-CoV-2 spike protein have been characterised and correlate well with IgG and IgA antibody titres in coronavirus patients.  This has important implications for vaccine design and long term immune response.

It is currently unknown whether antibody responses or T-cell responses in the infected person confer protective immunity.  If they do, it is also unknown how strong a response is needed for this to occur.

CD8+ T cells are the main inflammatory cells and play a vital role in virus clearance.  Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells and natural killer cells show a significant association with inflammatory status in COVID-19, especially the CD8+ T cells and CD4+, CD8+ ratio.  Decreased absolute numbers of T lymphocytes, CD4+ T cells, and CD8 T cells were observed in both mild cases and severe cases but accentuated in the severe cases.

In multivariate analyses, post-treatment decreases in CD8+ T cells and B cells and an increase in the CD4+, CD8+ ratio were indicated as independent predictors of poor treatment outcomes.  The expression of IFN-γ by CD4+ T cells also tended to be lower in severe cases than in moderate cases.

Antibody-Mediated Immune Response and Protective Immunity

The detection of antibodies to SARS-CoV-2 does not indicate directly protective immunity and correlates of protection for COVID-19 have yet to be established.

Most persons infected with SARS-CoV-2 display an antibody response between day 10 and day 21 after infection.  Detection in mild cases can take longer, up to four weeks or more and in a small number of cases antibodies i.e. IgM, IgG are not detected at all at least during this particular study’s’ timescale. 

Based on the currently available data, IgM and IgG antibodies develop between 6 and 15 days post disease onset.  The median seroconversion time for total antibodies, IgM and IgG were day 11, day 12 and day 14 post symptom onset, respectively.  The presence of antibodies was detected in less than 40% among patients within one week from onset, and rapidly increased to 100% total antibodies, 94.3% IgM and 79.8% IgG from day 15 after onset. 

The longevity of the antibody response is still unknown, but it is known that antibodies to other coronaviruses wane over time, the range being 12-52 weeks from the onset of symptoms and homologous re-infections have been shown. 

SARS-CoV-2 IgM and IgG antibody levels may remain over the course of seven weeks or at least in 80% of cases until day 49.  In comparison, 90% and 50% of SARS-CoV-1 infected patients have been shown to maintain IgG antibodies for two to three years respectively.  In addition, it could be important to detect nasal IgA antibodies, as the serum IgA antibodies were not raised, but IgA persisted in the nasal mucosa one year post-infection for seasonal coronavirus.

Reinfections with all seasonal coronaviruses occur in nature, usually within three years.  However, the elapsed time between infections does not mean that protective immunity lasted for the same period of time, because the reinfection was also dependent on re-exposure. 

Based on the minimum infection intervals and the observed dynamics of antibody waning, the study showed that the duration of protective immunity may last 6 to 12 months.  Primary infection with SARS-CoV-2 was shown to protect rhesus macaques from subsequent challenge and casts doubts on reports that the re-positivity observed in discharged patients is due to re-infection.

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