How do we show viral inoculum related to severity of disease? We can't do this with dangerous viruses like SARS-CoV-2 (only animal models like this one): pnas.org/content/117/28…
Don't think this relationship is true of all viruses, but seems to be true of some viruses where human experimentation was possible because they are not as dangerous (e.g. giving human volunteers doses of virus and showing that a higher dose gives more symptoms).
Here are few paper showing this for influenza with 'human inoculation" experiments: pubmed.ncbi.nlm.nih.gov/30770534
More- influenza: Watson. Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans. Virol J. 2015;12:13; Murphy. Dose response of cold-adapted, reassortant influenza A/California/10/78 virus (H1N1) in volunteers. JID 1984;149(5)
Also evidence for respiratory syncytial virus: Lee FE. Experimental infection of humans with A2 respiratory syncytial virus. Antiviral Res. 2004;63(3):191; Mills Experimental RSV infection of adults. Possible mechanisms of resistance to infection and illness. J Immunol. 1971;107
DeVincenzo. Viral load drives disease in humans experimentally infected with RSV. Am J Respir Crit Care Med. 2010;182(10); Couc .Effect hof route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriol Rev. 1966;30
Also papers on viral inoculum and disease severity for rotavirus, rhinovirus. Can only do human infection studies in volunteers with non-deadly viruses so can't be done for SARS-CoV-2: so watch epidemiologically if disease severity goes down with non-pharmaceutical interventions.
Therefore, to end this boring paper-laden thread, we are proposing hypothesis that viral inoculum related to disease severity in COVID-19 and that masks and social distancing decrease viral inoculum. End with one of my favorite epi studies on this: academic.oup.com/cid/advance-ar…
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