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SARS-CoV-2-reactive T cells are detected in some healthy unexposed individuals. Human studies indicate these T cells could be elicited by the common cold coronavirus OC43. To directly test this assumption and define the role of OC43-elicited T cells that are cross-reactive with SARS-CoV-2, we develop a model of sequential infections with OC43 followed by SARS-CoV-2 in HLA-B*0702 and HLA-DRB1*0101 Ifnar1−/− transgenic mice. We find that OC43 infection can elicit polyfunctional CD8+ and CD4+ effector T cells that cross-react with SARS-CoV-2 peptides. Furthermore, pre-exposure to OC43 reduces subsequent SARS-CoV-2 infection and disease in the lung for a short-term in HLA-DRB1*0101 Ifnar1−/− transgenic mice, and a longer-term in HLA-B*0702 Ifnar1−/− transgenic mice. Depletion of CD4+ T cells in HLA-DRB1*0101 Ifnar1−/− transgenic mice with prior OC43 exposure results in increased viral burden in the lung but no change in virus-induced lung damage following infection with SARS-CoV-2 (versus CD4+ T cell-sufficient mice), demonstrating that the OC43-elicited SARS-CoV-2 cross-reactive T cell-mediated cross-protection against SARS-CoV-2 is partially dependent on CD4+ T cells. These findings contribute to our understanding of the origin of pre-existing SARS-CoV-2-reactive T cells and their effects on SARS-CoV-2 clinical outcomes, and also carry implications for development of broadly protective betacoronavirus vaccines. The origin of SARS-CoV-2 cross-reactive T cells in unexposed humans is unclear. Here, the authors use HLA transgenic mouse models of sequential infections with human coronavirus OC43 and SARSCoV-2 and show that OC43 elicits cross-protective immunity against SARS-CoV-2, which partially depends on CD4 + T cells.

Published in Nature Communications (Jan. 26, 2024):

https://doi.org/10.1038/s41467-024-45043-2 

New evidence suggests that people who have had COVID-19 may be immune to SARS-CoV-2, the virus that causes it, for at least 5–7 months, if not longer. Recent alleged cases of reinfection with SARS-CoV-2, the coronavirus that causes COVID-19, have raised concerns that the human immune system may only provide short-term protection against the virus. In addition, scarce research has suggested that the number of antibodies in a person’s bloodstream that is capable of disabling the virus declines sharply after an initial infection. However, scientists at the University of Arizona (UArizona) College of Medicine in Tucson have now found evidence of long lasting immunity in people who have had COVID-19. 

They tested for the presence of antibodies to the virus in nearly 6,000 individuals and then followed them up for several months. “We clearly see high quality antibodies still being produced 5–7 months after SARS-CoV-2 infection,” says Dr. Deepta Bhattacharya, an associate professor of immunobiology at the university, who co-led the research.  “Many concerns have been expressed about immunity against COVID-19 not lasting. We used this study to investigate that question and found immunity is stable for at least 5 months.”  Bhattacharya points out that people who contracted the SARS-CoV virus responsible for the 2002–2004 outbreak of SARS were still immune 12–17 years after infection. This virus is very similar to SARS-CoV-2.  “If SARS-CoV-2 is anything like the first one, we expect antibodies to last at least 2 years, and it would be unlikely for anything much shorter,” he says.  In their paper, published in the journal Immunity, the scientists also note that out of nearly 30 million cases of COVID-19 since December 2019, there have been only about 10 confirmed cases of reinfection...

Study published in Immunity (Oct. 13, 2020):

https://doi.org/10.1016/j.immuni.2020.10.004

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