Clara Gitahy Falcao Faria, eta al.

Med Hypotheses . 2021 Jan 24;148:110508. doi: 10.1016/j.mehy.2021.110508. Online ahead of print.

Some studies demonstrate that psychoactive drugs may protect from SARS-CoV-2 infection. H1 antihistamines and cationic amphiphilic drugs (CAD) have been identified as potentially effective against coronavirus. CAD lead to intracellular trafficking disturbances, which disrupt viral entry and replication.

Many antihistamines are also CAD, acting on both virus entry and exerting a negative regulation on IL-6 release from human lung macrophages, which are secreted in great amounts during the cytokine-storm of COVID-19.

H1 antihistamines in general and phenothiazines and derivates, in particular, can represent a useful strategy against SARS-CoV-2 at different stages, from the prophylaxis to complications’ prevention. Also, a sample of 219000 health records demonstrated that three antihistamines (azelastine, diphenhydramine, and hydroxyzine) were associated with reduced incidence of SARS-CoV-2 in people older than 61.

Although more recent studies suggest that a psychiatric disorder can increase the risk of COVID-19 or developing a severe form, the authors came to the assumption that mental health patients, once hospitalized due to COVID-19, have their risk increased due to the possible reduction or interruption of medications with a potential effect against SARS-CoV-2.

In conclusion, the best tolerated drugs with few side effects can become prophylactic candidates to reduce the risk of infection by SARS-CoV-2 in the general population. However, the benefit-risk should always be assessed.

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