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What role does previous exposure to seasonal coronaviruses play in disease severity for COVID-19?
New paper (great thread from @VirusesImmunity below) provides some evidence, but I don't think it can explain age or sex (or other) variation in disease severity.
Thread https://twitter.com/VirusesImmunity/status/1325085193913462784
New paper (great thread from @VirusesImmunity below) provides some evidence, but I don't think it can explain age or sex (or other) variation in disease severity.
Thread https://twitter.com/VirusesImmunity/status/1325085193913462784
Background
COVID-19 (the disease) is caused by infection w/ SARS-CoV-2, a betacoronavirus. Why does this matter? Because there are 2 other betacoronaviruses that infect humans frequently (OC43 & HKU1) & cause common cold.
COVID-19 (the disease) is caused by infection w/ SARS-CoV-2, a betacoronavirus. Why does this matter? Because there are 2 other betacoronaviruses that infect humans frequently (OC43 & HKU1) & cause common cold.
HUGE Outstanding Q: does infection w/ seasonal coronaviruses provide "protection" against SARS-CoV-2?
Earlier studies showed that immunity against coronaviruses sometimes wanes over 6-12 mo, so full protection is not always long lasting.
@HuangAngkanaT https://www.nature.com/articles/s41467-020-18450-4
Earlier studies showed that immunity against coronaviruses sometimes wanes over 6-12 mo, so full protection is not always long lasting.
@HuangAngkanaT https://www.nature.com/articles/s41467-020-18450-4
Also, it's very clear that pre-existing immunity from seasonal coronaviruses doesn't provide "sterilizing immunity" (preventing infection & disease) against SARS-CoV-2 b/c attack rate sometimes very high ( https://twitter.com/DiseaseEcology/status/1289298074804711425).
But experimental reinfections w/ seasonal coronaviruses were often less severe, raising possibility that even if previous exposure doesn't always provide long lasting sterilizing immunity it might reduce disease severity.
https://www.nature.com/articles/s41467-020-18450-4
https://www.nature.com/articles/s41467-020-18450-4
Also see early @mlipsitch NYT article for layperson-friendly description of coronavirus immunity. https://www.nytimes.com/2020/04/13/opinion/coronavirus-immunity.html
For COVID-19 there is huge variation in disease severity both w/ age (1000x range of fatality: https://twitter.com/DiseaseEcology/status/1252844190070829056) & even w/in same age group. A big outstanding Q is: What causes this variation?
Immunity to seasonal coronaviruses has been proposed as 1 possibility. But it's not a simple explanation. Most people have been exposed to all 4 seasonal coronaviruses by the time they are teenagers ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593164/). So why don't we all have some immunity to SARS-CoV-2?
Here's data for all 4 seasonal coronaviruses (fitted models are very strange - focus on the data).
https://www.nature.com/articles/s41467-020-18450-4
https://www.nature.com/articles/s41467-020-18450-4
One possibility is that we get exposed to seasonal coronaviruses when young which gives robust immune response (that might be protective against SARS-CoV-2) but this fades over time so kids are protected but older people aren't.
New paper looking at presence of antibodies (Ab) from seasonal coronaviruses that are cross-protective against SARS-CoV-2 suggests this might be the case. Thread above by @VirusesImmunity covers several issues; I'll focus on one key issue here... https://science.sciencemag.org/content/early/2020/11/05/science.abe1107
Prevalence of cross-reactive Ab was high for 6-16, but lower for 17+ & 0-5 (N small in 0-5).
This *could* explain lower susceptibility & disease severity in fraction of kids 6-16 & possibly lower infectiousness if cross-immunity lowers infectiousness. But...
This *could* explain lower susceptibility & disease severity in fraction of kids 6-16 & possibly lower infectiousness if cross-immunity lowers infectiousness. But...
prevalence of infection w/ seasonal coronaviruses is 2x higher in 0-4 than 5-15yr & infection similar for all ages >5yr (Left: https://wellcomeopenresearch.org/articles/5-52/v1). Thus it's puzzling why cross-reactive Ab would be higher in 11-16 than adults which have same infection prev as all ages >5yr.
In other words, it can't be as simple as: exposure to seasonal coronaviruses is higher in kids than adults so kids have higher cross-immunity Ab. Age of higher infection (0-4y) & highest cross immunity (6-16y) doesn't line up.
Also why doesn't similar inf. prev in adults 45-65+ as 5-44yr provide similar protection in these groups? 1 possibility is differential response to seasonal coronavirus infection across ages. But diff immune response could explain age-specific disease severity independently, so..
previous exposure to seasonal coronaviruses wouldn't be needed as explanation. It could contribute; it could be irrelevant. Same for explanation of variation in disease severity w/in age group. Only 5% of adults have cross-reactive Ab. Occam's razor would lean against it.
Thus, while this new study ( https://science.sciencemag.org/content/early/2020/11/05/science.abe1107) shows that some people (20-60% in 0-16y; 5% in 17-76y) have cross-reactive Ab against SARS-CoV-2 from exposure to seasonal coronaviruses I don't think it explains age- or sex-specific or w/in age group variation in COVID-19.
If I've missed something or misunderstood something here please let me know. @MackayIM @datcummings @HuangAngkanaT
