Association of benzodiazepines with SARS-CoV-2 positivity and clinical outcomes in three patient groups

To date, the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed more than six million lives worldwide. It has dramatically affected the global economy and the healthcare system. A range of symptoms is associated with SARS-CoV-2 infection, such as asymptomatic, mild, moderate, and severe. 

Scientists have indicated that individuals aged 65 years or above and those with comorbidities, such as chronic obstructive pulmonary disease (COPD), hypertension, asthma, cardiovascular disease, chronic kidney disease, diabetes, obesity, cancer, etc., are at a higher risk to develop severe SARS-Cov-2 infection.

Benzodiazepines and respiratory illness

Previous studies have reported that individuals who use benzodiazepines (BZD) and BZD receptor agonists are at a higher risk of suffering severe pneumonia and death due to pneumonia. These studies have also indicated an increased possibility of developing respiratory depression in people who use BZD and have pre-existing respiratory problems. Similarly, COPD patients who use BZD have been found to be at an increased risk.

Although few studies have focussed on evaluating the role of BZD in COVID-19 patients, the results have been inconsistent. BZD is a commonly used medicine for sedation or used in the treatment of anxiety and other mental illness. Hence, it is important to investigate the influence of BZD on the clinical outcomes of SARS-CoV-2 patients. 

Benzodiazepines and COVID-19: a new study 

A new study currently posted to the Research Square* preprint server while under consideration for publication at the BMC One Health Outlook journal has evaluated the association of BZD use with the clinical outcomes of SARS-CoV-2 positive patients.

In this study, scientists utilized nationwide cohort data from South Korea and evaluated three groups of COVID-19 patients. These groups were (a) those who required hospital admission, (b) those with severe symptoms requiring intensive unit care (ICU), and (b) those who died due to severe disease.

Scientists obtained National Health Information Database (NHID)-COVID data from National Health Insurance Service (NHIS) between 2015 and 2020. The study cohort, which comprised a total of 328,373 individuals, was divided into two groups, i.e., individuals who did not use BZD and individuals who used BZD. These two groups were matched via propensity scores.

Scientists reported that 44·4% of the study cohort were men and 55·6% were women. The majority of participants were around 20–39 years of age. Additionally, researchers estimated that 59·1% of the study cohort had various comorbidities. Interestingly, in a nationwide cohort study from South Korea, scientists reported that 87·7% of BZD prescriptions were related to non-psychiatric diagnoses.

In this study, scientists identified the association between BZD use and the risk of SARS-CoV-2 positivity. After propensity score matching (PSM), they reported that the association between BZD use and the risk of SARS-CoV-2 positivity was not detected. Interestingly, models also predicted that there were no associations between chronic BZD use and the risk of SARS-CoV-2 positivity.

The authors reported that 5·5% of the BZD use group died while 10·3% required ICU or invasive ventilation support. 87·4% of COVID-19 patients who used BZD had required hospitalization. Importantly, scientists observed that after adjusting for potential confounding variables, the BZD use group was at a higher risk of requiring hospitalization due to COVID-19 compared to those who did not use BZD.

Implications

Scientists revealed that the chronic use of BZD resulted in an increase in the risk of requiring hospitalization among COVID-19 patients. They further highlighted that the use of BZD did not significantly influence the risk of SARS-CoV-2 infection, severe outcomes, or mortality.

The findings of this study are in line with previous research that reported BZD use increased susceptibility to superinfections associated with influenza-infected animals and humans.

Scientists revealed that the underlying mechanisms of this association could be related to the effects of BZD on the immune system. The main advantage of this study is that it could aid in developing strategies for managing COVID-19 patients associated with chronic BZD usage, i.e., who are at a higher risk of hospitalization.

Limitations

The authors highlighted some of the limitations of this study, which include possible miscalculations regarding the estimates of hospitalization of COVID-19 patients under BZD medication. Owing to the unavailability of data related to the BZD dosage and hospitalization period, scientists failed to make a full assessment. Additionally, as new data on clinical outcomes were not included, the effect of SARS-CoV-2 variants infection in individuals under BZD use could not be analyzed.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.