Repurposing Candidate Drugs to Prevent SARS-CoV-2: A PharmLines Test-Negative Case-Control Study

Area of Science:

• Infectious Diseases
• Pharmacology
• Public Health

Background:

• Emerging SARS-CoV-2 variants necessitate accessible, low-cost COVID-19 prevention strategies.
• Drug repurposing is a time-efficient approach, but clinical data for existing drugs is limited.
• The PharmLines Initiative enabled assessment of 42 candidate drugs' association with COVID-19 infection.

Purpose of the Study:

• To evaluate the association between 42 candidate drugs and COVID-19 infection.
• To investigate potential effect modification by SARS-CoV-2 variants and vaccination status.

Main Methods:

• Test-negative case-control study using Lifelines cohort and IADB.nl dispensing data.
• Matched cases (RT-PCR positive) and controls (RT-PCR negative) for age, sex, and testing date.
• Multivariable conditional logistic regression with subgroup analyses for variant and vaccination effects.

Main Results:

• None of the 42 drugs were associated with protection against SARS-CoV-2 infection.
• Chronic use of calcium channel blockers, diuretics, and metformin showed increased risk for original strain SARS-CoV-2 infection.
• No significant associations were found when stratified by COVID-19 vaccination status.

Conclusions:

• No studied drugs demonstrated protective associations against SARS-CoV-2 infection.
• Certain antihypertensives and metformin were associated with an increased risk of infection.
• Findings do not support off-label use of these drugs for COVID-19 prophylaxis in the general population.