Thread by @MonicaGandhi9

Wanted to talk to you about our #inoculum hypothesis and may have particular relevance in the vaccine era. Our idea was -after seeing that mitigation procedures like masks didn't always block transmission especially if just cloth or plain surgical, but seemed associated with less

severe disease and more asymptomatic infection - was that if you are exposed to less viral inoculum or dose, more likely to get mild disease. We first explored this hypothesis here and then, given that even asymptomatic or mild infection triggered T cells,
link.springer.com/article/10.100…

we hypothesized that anything that would drive the infection towards asymptomatic or mild (if unlucky enough to be exposed) while awaiting a vaccine was helpful -e.g. nonpharmaceutical interventions (NPIs) like masks nejm.org/doi/full/10.10…

We saw this in a study of a business that never closed (even during surges) but applied masks, distancing and ventilation, and saw very little severe disease (even in places of high incidence at time)
academic.oup.com/ofid/article/8…

We explored this more in this Lancet ID article where we looked at the relationship between inoculum and either developing infection at all or the severity of disease with other pathogens - noting when this is seen & comparing this to COVID-19
thelancet.com/journals/lanin…

Here is additional evidence to support our hypothesis- in Hong Kong study where universal mask wearing adopted, most transmission occurred in households & infections that occurred in masked settings more likely to be asymptomatic
journalofinfection.com/article/S0163-…

So how is this relevant to vaccine era? If severity of infection modulated by host (co-morbidities) but also degree of inoculum, even in half-vaccinated (one-dose), a high inoculum could lead to symptomatic or severe infection (e.g. health care workers in India after 1 dose).

Means masking & mitigation procedures in places with high transmission can be different than in places with low transmission (e.g. unvaccinated inside in public very different risk in SF versus India). And someone nonimmune or partially immune can be overwhelmed by inoculum

And why in places of high transmission, inside, a fitted and high filtration mask is needed to more effectively block transmission (instead of only partially)- cloth+surgical; cloth with filter inside; N95:
sciencedirect.com/science/articl…