During the COVID-19 pandemic Ayyadurai used social media to spread various conspiracy theories and misinformation about the pandemic. In January 2020 he claimed that the coronavirus was patented by the Pirbright Institute, but the patent he referenced relates to avian coronavirus, which infects birds, not SARS-CoV-2, the virus responsible for the pandemic.[50] Ayyadurai defined COVID-19 as "an overactive dysfunctional immune system that overreacts and that's what causes damage to the body", and claimed that vitamin C could be used to treat it.[51]

He alleged that the coronavirus was spread by the "deep state" and accused Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, of being a "Deep State Plant". Ayyadurai called for Fauci to be fired[52] and his supporters lobbied for Fauci to be replaced by Ayyadurai.[53]

In March 2020 he published an open letter to president Donald Trump where he wrote that a national lockdown was unnecessary and advocated that large doses of vitamins could prevent and cure the disease.[54] In April 2020, Politico and Vanity Fair reported that QAnon supporter DeAnna Lorraine recommended that Shiva be included in coronavirus discussions at Donald Trump's White House.

Going to stick with sane sources if that’s okay