1/Epi studies show striking age differences in #COVID19 cases. In China, only 2% are <20 yrs old (Wu, JAMA). Relative risk is much higher above 30 (Sun, LancetDigHealth). It's likely kids are infected but have mild or no symptoms. We need more data from outside China to confirm.
2/Why are #COVID cases detected more often in adults? Older adults have higher risk due to frailty and aging immune system. But this does not explain increased risk across all adult age groups vs children. One possible explanation might be antibody dependent enhancement (ADE).
3/Dengue #virus is a good example of ADE. There are 4 dengue serotypes, and infection generates protection only against the same serotype (no cross-protection). Later infection with a different serotype is a risk factor for more severe disease: dengue hemorrhagic fever.
4/The idea is that antibodies from earlier infection cross-react and bind viruses without neutralizing. The antibody complexes infect immune cells and cause damage. For dengue, pre-existing antibody level must be within a narrow range for this to occur (Katzelnick, Science 2017).
5/There is evidence for ADE in 2003 SARS. SARS-CoV antibodies increase immune cell infection with SARS virus (Yip VirolJ 2014). In Taiwan, SARS patients with early antibody rise had a higher death rate, possibly due to priming from pre-existing SARS-CoV antibody (Ho, EID 2005).
6/Many people are infected with seasonal CoVs each winter. Most are mild and self-limited. Seasonal CoV antibody titers are higher in adults than children (Schmidt, AJE 1986). SARS-CoV antibody cross-reacts with seasonal CoV 229E but not OC43 (Ksiazek NEJM 2003).
7/Is it plausible that seasonal CoV antibodies (esp 229E) cause ADE and increase #COVID19 risk in adults more than children? Jason Tetro (preproof, Microbes&Inf) argues that ADE may occur due to prior SARS-CoV antibodies. IMO this is unlikely, but seasonal CoV might contribute.
8/It would be great to hear from @VirusWhisperer @florian_krammer @MackayIM and others on this. There is an urgent need for seroepidemiology studies to understand immune response and age, #COVID19 severity. Results will guide public health response and vaccine development. [end]
