CYP2D6 and CYP3A4 variants influence the risk and outcome of COVID-19 infection among rheumatoid arthritis patients maintained on hydroxychloroquine.

OBJECTIVES

Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA).

METHODS

A total of 60 patients were genotyped for CYP2D62XN, CYP2D64, CYP3A41B and CYP3A52. They were receiving HCQ for the treatment of RA. The patients were evaluated clinically for fever and dry cough, radiologically via chest computed tomography (CT) and immunologically via anti-Covid-19 IgG and IgM titers.

RESULTS

Variants in CYP2D6 significantly affected the grade of ground glass (CYP2D64 AA carriers showed the higher risk for grade 3) and the risk of positive anti-Covid-19 IgM (CYP2D62XN CC and CYP3A4*1B AA had the lowest risk), the duration of HCQ, the use of corticosteroids or gender did not affect the Covid-19 status significantly.

CONCLUSIONS

In general, the outcome of the studied patients receiving HCQ was good (no deaths, no intubation needed). CYP2D6 variants could affect the outcome of Covid-19 infection.