In a new study published on the preprint server medRxiv*, researchers investigate a number of drugs that are believed to potentially worsen outcomes in patients with coronavirus disease 2019 (COVID-19). To this end, the researchers used a rapid systematic review and meta-analysis approach to identify and assess any potentially deleterious drug groups in COVID-19 susceptibility and prognosis.
Study: Deleterious drugs in COVID-19: a rapid systematic review and meta-analysis. Image Credit: VonaUA / Shutterstock.com
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Interestingly, when looking for these drugs, the researchers found that individuals on prior medication with angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) required little care when infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which is the causative agent of COVID-19.
Taken together, none of the drugs assessed in the current study increased the severity of related afflictions with COVID-19. The study reports there was minimal high quality or consistent evidence showing that any of the drug groups increased susceptibility, severity, or mortality in COVID-19.
Background
Since December 2019, SARS-CoV-2 has infected over 231 million individuals and caused over 4.74 million deaths globally. Along with the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 is one of three zoonotic human beta coronaviruses that has emerged in the last 20 years.
SARS-CoV and SARS-CoV-2 enter the human host cell via the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of host cells. As a result, ACE2 has received renewed attention as a possible target for anti-viral therapeutics. To this end, it has been hypothesized that drugs that upregulate ACE2 may increase the risk of severe SARS-CoV-2 infection.
Many studies observed that a number of drugs alter the progression of COVID-19 in both positive and negative ways. For example, negative effects of drugs can increase the likelihood of COVID-19 patients developing acute respiratory distress syndrome (ARDS), require mechanical ventilation (MV), or complications such as multi-organ failure, often requiring intensive care unit (ICU) in severe cases.
Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immunosuppressants, ACEIs, and ARBs have been in use to treat COVID-19 with conflicting inferences and observations. Additionally, scientific papers published prior to peer review rushed in a lot of information, which led to questions on their scientific validity.
In this context, the current study sheds light on understanding the gaps in the research and notes the effects of the drugs in COVID-19.
“We aimed to identify, critically appraise and synthesize the evidence on drugs which may be deleterious in COVID-19."
About the study
In the current study, the researchers performed a rapid systematic review of primary studies investigating drugs identified as potentially deleterious. To this end, Medline, Embase, and WHO (World Health Organization) COVID-19 database, and NIH iSearch COVID-19 portfolio were used to find papers and preprints for the study, using the Population, Exposure, Comparison, Outcome, Study (PECOS) format.
Because new research on this topic is published at an exponential rate, the researchers adopted a rapid review methodology following the Cochrane rapid review protocol, with the aim of producing reliable results in a timely fashion.
First, the researchers tried to amass a list of drugs hypothesized as potentially harmful in COVID-19. Second, they used terms to capture evidence in the WHO database related to all the drugs identified. Primary outcomes were defined as direct measures of susceptibility to infection, disease severity, and mortality.
Overall, the researchers identified 63 papers with primary data related to these drugs. Of these, 49 papers measured at least one primary outcome included in the study. Notably, 51% of these papers were from China.
Principal findings
The researchers identified eight drug groups that were hypothesized to be deleterious in COVID-19. These comprised ACEIs, ARBs, corticosteroids, immunosuppressants, mineralocorticoid receptor antagonists (MCRAs), NSAIDs, statins, and thiazolidinediones (TZDs).
This study suggests that individuals without COVID-19 should not discontinue their medications to reduce their risk of contracting the virus, as there is no evidence for this. Similarly, immunosuppressants should also be not stopped, as they may lead to a flare of the person’s underlying condition, which can result in an increased risk of infection.
“Furthermore, the withdrawal of any necessary medications could cause harm from the disease the drug was being used to treat, as well as from a potentially severe form of COVID-19 for people with hypertension and diabetes who are already at increased risk.”
ACEIs and ARBs together are referred to as renin-angiotensin-aldosterone blockers (RAASBs). Individuals on RAASBs were found to have quick viral clearance and reduced hospital stay. The study also highlighted the gaps in the research, such as the lack of randomized controlled trials (RCTs) and mortality data for NSAIDs, immunosuppressants, and long-term steroid use.
While discussing the best available evidence obtained in this study, the researchers also highlighted the limitations here, most of which stemmed from the quick publications and rapid analysis methodologies.
*Important notice: medRxiv 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.
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