Early on in the COVID-19 pandemic, in March 2020, researchers based in the United States discovered that SARS-CoV-2 (the virus that causes COVID-19 infection) uses the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry to its hosts’ cells.
This was a watershed moment but it also raised concerns over the safety of using renin-angiotensin system (RAS) blockers, since these could increase the expression of ACE2 — the hypothesis being that this could lead to an increased risk of acquiring COVID-19.
With media attention, these safety concerns were spread widely, and many patients taking RAS blockers on a long-term basis started to call into their pharmacy, worried about continuing their medication.
Amid a dearth of evidence, this posed a dilemma for our pharmacist colleagues. We needed data, and fast. So, this is where the evidence synthesis started for our team of pharmacist researchers from across the UK (Huddersfield, Leeds, Birmingham and Sheffield) and the world (Malaysia, Australia and Italy).
From our literature review, we found that the increased expression of ACE2 is not a consistent finding with the use of RAS blocker, and that ACE2 may be protective towards lung injuries induced by the virus. After risk-benefit assessments, we concluded that RAS blockers shouldn’t be stopped merely to avoid the unfounded fear of acquiring COVID-19.
Later, with more evidence published on COVID-19 patients, we produced a thorough systematic review and meta-analysis analysing more than 50 studies that evaluated the effect of RAS blockers in COVID-19, which discredited the safety concerns associated with the use of RAS blockers altogether.
Next, we investigated chloroquine and hydroxychloroquine, with or without combination with azithromycin. These existing drugs were touted in the media as potentially life-saving in COVID-19 infection, and we foresaw how this could result in them being hoarded unnecessarily and kept from the patients who need them — particularly patients with rheumatic diseases.
Again, we critically reviewed the clinical and scientific evidence around the use of antimalarials in COVID-19, producing a narrative review on the topic, in which we recommended that the use of antimalarials should be evaluated in the setting of clinical trials. We also strongly urged pharmacists across the world to dispense the drugs responsibly.
The next concern was corticosteroids. Later in March 2020, the World Health Organization (WHO) recommended against the routine use of systemic corticosteroids in the clinical management of COVID-19, citing the fear of the delay in viral clearance and other potential harms. As a result, there were concerns over the continued use of inhaled and oral corticosteroids in patients with asthma and chronic obstructive pulmonary disease (COPD).
But with our previous experience in dealing with the rapid escalation of safety concerns around RAS blockers, our research team was among the first few to synthesise available evidence on the use of these drugs in this group of patients. Our risk-benefit assessment led us to conclude that the benefits of continuing corticosteroid treatment outweigh the uncertain risks in the context of the COVID-19 pandemic. We therefore recommended that asthma and COPD should continue to be managed in the usual way.
In COVID-19-infected patients, however, WHO recommended that the routine use of systemic corticosteroids should be avoided. But when we scrutinised the evidence WHO cites as the basis of its recommendation, we found that the findings on the efficacy of systemic corticosteroids in COVID-19 were inconclusive. We believe that it may be too early to discard corticosteroid therapy in our armory against COVID-19.
To this end, we synthesised evidence related to the use of systemic corticosteroids in COVID-19, proposing that systemic corticosteroids may be worth a trial in COVID-19 patients who develop acute respiratory distress syndrome (ARDS). We were also the first to report pooled mortality estimates in COVID-19 patients with ARDS in our meta-analysis. Our research work was cited by
BMJ Best Practice
to substantiate their similar recommendation. The WHO later overturned their previous recommendation to recommend systemic corticosteroid use in patients with severe COVID-19.
As well as these important research works, we have synthesised evidence on many aspects of care in COVID-19, including the use of proton pump inhibitors and statins in COVID-19 patients; and this evidence has also been cited by BMJ Best Practice. We also produced evidence-based practical guides on the use of cardiovascular drugs in COVID-19 patients, the use of antidiabetic drugs in hospitalised COVID-19 patients and the management of co-medications in COVID-19 patients with atrial fibrillation.
All in all, between March 2020 and November 2020, we produced more than 50 articles, including evidence-based reviews, commentaries on published studies, systematic reviews, meta-analysis and original studies — with a cumulative impact factor (of the journals that published our work) of more than 190. More than two-thirds of our articles have featured in Q1 and Q2 journals — those that are ranked in the top half of scientific publications.
Although 2020 has given us unprecedented temptation to overrule the evidence-based approach, we have been steadfast to uphold it. As pharmacists — the guardians of safe medicine use — it’s our duty to defend evidence-based medicine, even amid the uncertainty in 2020.
Syed Shahzad Hasan, PhD, Department of Pharmacy, University of Huddersfield
Chia Siang Kow, BPharm, School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
Our COVID-19 research papers are available at: https://www.researchgate.net/project/COVID-19-and-the-use-of-medicines
Acknowledgments: Hamid Merchant, University of Huddersfield, UK; Toby Capstick, Leeds Teaching NHS Hospital, UK; Syed Tabish Razi Zaidi, University of Leeds, UK; Wendy Sunter, Calderdale and Huddersfield NHS Foundation Trust, UK; Muhammad Abdul Hadi, University of Birmingham, UK; Kaeshaelya Thiruchelvam, University of Newcastle, Australia; Faizan Mazhar, UniversitÃ degli Studi di Milano, Italy; Mamoon Aldeyab, University of Huddersfield; Amie Bain and Sallianne Kavanagh, Sheffield Teaching Hospital and University of Huddersfield, UK