Susceptibility to and severity of SARS-CoV-2 infection according to prescription drug use-an observational study of 46,506 Danish healthcare workers

Abstract

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers. SARS-CoV-2 positivity was defined as a positive PCR/ELISA test throughout 2020 and severe COVID-19 as any above 48-hour hospitalization within 14 days after infection. Patient characteristics came from online surveys while data on SARS-CoV-2, drugs and hospitalizations came from Danish Health Registers. Infected individuals were matched with uninfected controls based on age, sex, and chronic diseases. Drug exposure was defined as any prescription redemption in the past six and one month(s) before infection for each drug class. Models assessing the risk of infection (conditional logistic regression) and severe COVID-19 (logistic regressions) versus drug usage were adjusted for BMI, smoking, alcohol, education, region, and patient contact when possible. We matched 5,710 SARS-CoV-2-infected cases with 57,021 controls. The odds of infection were reduced by calcium channel blocker (adjusted odds ratio (aOR) 0.81, 95% Confidence Interval (CI): 0.66-1.00) and vasoprotective drug (aOR 0.77, CI: 0.62-0.95) usage during the six months before infection compared to no usage. Exposure to antibacterials in the past month increased the odds of infection (aOR 1.27, CI: 1.09-1.48). Among infected participants, the odds of severe COVID-19 were higher with usage of almost any investigated drug, especially, diuretics (crude odds radio (OR) 4.82, CI:2.15-10.83), obstructive airway disease drugs (OR 4.49, CI: 2.49-8.08), and antibacterials (OR 2.74 CI:1.62-4.61). In conclusion, antibacterials were associated with more SARS-CoV-2 infections and calcium channel blockers with less. Once infected, users of prescription drugs had higher odds of developing severe COVID-19. These findings suggest a need for studies to clarify interactions between specific drug groups, behaviour, known risk factors, and disease susceptibility/severity.

Fig 1. Flowchart of the inclusion process.

Flowchart of the inclusion process of healthcare workers. *Defined based on PCR tests only. Severe COVID-19 was defined as any hospital admission longer than 48 hours with time of admission within 14 days after the positive SARS-CoV-2 test result. **Defined based on PCR tests and ELISA tests. Abbreviations: PCR, polymerase chain reaction. SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2.

Fig 2. Adjusted odds ratios of SARS-CoV-2 positivity according to prescription drug use.

Adjusted odds ratios for having a positive SARS-CoV-2 test (PCR or ELISA) according to use of prescription drugs (yes/no) in the six months before date of infection, compared to controls matched on sex, age and chronic diseases. Prescription drug categories are based on the Anatomical Therapeutic Chemical Classification System as defined by the World Health Organization (codes are listed in parenthesis). The analysis was adjusted for body mass index (BMI) (<18.5, 18,5–25,25–30, >30 kg/m², missing), smoking (yes, no, former smoker, missing), alcohol intake (0, 0–7, 7–15, >15 units per week, missing), educational level (none or short, middle, long, missing), patient contact (none, partly, full time, missing), and region of employment (Capital Region or Region Zealand). *) Indicates SARS-CoV-2 positive fraction in percent of drug users and no-drug users, respectively. Abbreviations: Adj., adjusted. OR, odds ratio. PCR, polymerase chain reaction. SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2.

Fig 3. Odds ratios of severe COVID-19 according to prescription drug use among 4,114 infected participants.

Crude odds ratios of a severe COVID-19 infection when comparing use versus no use (reference) of prescription drugs in the six months prior to a PCR SARS-CoV-2 positive test. Severe COVID-19 was defined as hospitalization for more than 48 hours with time of admission within 14 days of a positive SARS-CoV-2 PCR test.