key: cord-0990262-7uax2rci
authors: de Brouwer, Remco; van Veldhuisen, Dirk J.; de Boer, Rudolf A.
title: Surviving the first COVID‐19 wave and learning lessons for the second
date: 2020-06-21
journal: Eur J Heart Fail
DOI: 10.1002/ejhf.1938
sha: 4956fbe6c88fddb7f6740815628a2120dbc6b4ef
doc_id: 990262
cord_uid: 7uax2rci

nan

for it to infect a cell 3, 4 . However, other studies have suggested rather the opposite 5, 6 , and the use of ACEi or ARBs in heart failure was not associated with higher ACE2 levels 7 . Bean et al. report in this issue of the Journal the results of their multicentre cohort study aimed at investigating whether chronic treatment with ACEi and ARBs would increase the severity of COVID-19 infections 8 . The authors note that data on the clinical characteristics of hospitalized COVID patients shows an overrepresentation of cardiovascular comorbidities, which suggests an increased risk of severe disease progression among this population. The widespread usage of ACEi and ARBs in western countries is mentioned by the authors as an important reason for investigating the existence of a relationship between chronic usage of these drugs and COVID-19 disease severity, and whether this relationship is a harmful one.

The authors enrolled a cohort of 1200 COVID-19 adult inpatients at King's College Hospital and Princess Royal University Hospital who all tested positive for SARS-Cov2 by RT-PCR. Patients were only included if they were symptomatic at presentation, and the primary endpoint was defined as either death or admission to a critical care unit within 21 days of symptoms onset. Clinical notes, letters, and medication orders were reviewed to determine whether patients were chronically treated with ACEi or ARB, and the primary endpoint was manually verified by a clinician. Of the 1200 patients enrolled, 75% had at least one comorbidity and 33.2% were chronically treated with an ACEi or ARB. While the crude analysis did not show an effect of these drugs on disease severity (OR 0.83 [0.64-1.07]), adjusting for age and sex revealed a significant effect: the patients on ACEi and ARBs appeared to achieve better outcomes than the patients not receiving those drugs (OR 0.70 [0.53-0.91], p<0.01), and additional adjustments based on comorbidities strengthened this effect even further (OR 0.63 [0.47-0.84], p<0.01); results are summarized in figure 1. As the authors note, these findings suggest chronic treatment with ACEi and ARBs does not harm COVID-19 patients and may even have a beneficial effect on disease progression. This is important information: discontinuation of these medications due to fears of increasing the patients' susceptibility to COVID cannot be recommended and may not be without risk. This is not the first article on this topic, but we believe this publication to be particularly relevant for practitioners located in Europe: an ethnically mixed population with significant proportions of the various ethnicities helps ward off bias, and we expect the prevalence of chronic ACEi and ARB usage in two large U.K.-based hospitals to mirror the usage rates of other western countries. The large cohort size allowed the authors to adjust for age and comorbidities, which allows the results to translate to clinical practice more easily. There are several limitations to this study as well: though the cohort was treated at two different hospitals, both are centres located in London which makes it difficult to apply the results to other (more rural) regions. Excluding patients not ill enough to require hospitalisation also means the investigated drugs' possible effects on the disease progression of less severe COVID-19 infections will remain unknown. The authors set out to investigate whether there is a harmful relationship between these drugs and COVID-19 disease severity however, and their results show that both ACEi and ARBs can be safely continued without increasing the risk of a Accepted Article poor outcome. While the authors are quick to mention these retrospective data should be validated in prospective studies before they can become part of common medical practice, the observation that treatment with ACEi and ARB may result in better outcomes in a 'respiratory infection' is still intriguing. At the very least, it challenges the view that COVID-19 is merely a respiratory disease. The possible beneficial effect of these drugs in patients with ARDS, for example due to the hypothesised inhibition of RAS activation 9 , might lead to interesting future ways to treat this syndrome, if supported by future trials.

So on a broader scope, it is our opinion that these results support the inclusion of cardiological expertise to COVID-19 teams. Due to the prevalence of cardiovascular comorbidities and the frequent usage of cardiac medications in older patients, many clinical decisions for patients suffering from COVID-19 will impact cardiovascular health status and medications. Complex CV patients with many comorbidities are difficult to manage as-is, let alone during a viral pandemic. With routine care being set back, it will likely pay off to invest in these patients.

Further, in more general terms, during the height of the first wave, minimizing infections and maximizing treatment capacity were our top priorities, for good reason. However, we should also (no longer) ignore the collateral damage caused by putting routine care on hold -also since we have more data on the direct effects of scaling down routine care 10, 11 . We have learned a certain number of deaths cannot be directly attributed to COVID-19. Though it is possible that part of that excess mortality is still directly caused by COVID-19 cases -persons who were not tested but were infected -it is likely that allocating resources away from routine care in combination with weeks of government-issued bulletins telling people to stay away from public areas like hospitals as much as possible may have caused negative effects on public health by itself. For instance, we have seen a substantial reduction in PCI lab activations across Europe 12, 13 , and attributing this decrease to a lower incidence of STEMI is unrealistic. Similar observations have been made for heart failure: lower admission rates, but a higher incidence of NYHA III or IV symptoms 14, 15 .

So, now that things have appeared to calm down, we should look at our actions during the first wave and try to learn as much as possible from the decisions we have made. As healthcare practitioners, we should strive to continue regular care, if possible, the second time around. And we plea for COVID (crisis) teams to include cardiological expertise. If a second COVID-19 wave does eventually arrive -although we all hope this will not happen -we can and must be better prepared learning from the valuable and costly experiences during the COVID-19 pandemic of 2020.

None Accepted Article Figure 1 : A substantial proportion of the patients in the study of Neal et al. used ACEi or ARBs. But the use of ACEi or ARBs in COVID-19 patients was not associated with an overall unfavorable outcome.

Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme

Multiple Functions of Angiotensin-Converting Enzyme 2 and Its Relevance in Cardiovascular Diseases

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19

Urinary angiotensin-converting enzyme 2 in patients with CKD

Circulating ACE2 activity correlates with cardiovascular disease development

Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors

ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust

Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19

Excess deaths during the Covid-19 pandemic: An international comparison

Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19: the pandemic response causes cardiac collateral damage

Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy

Admission of patients with STEMI since the outbreak of the COVID-19 pandemic. A survey by the European Society of Cardiology

The impact of COVID-19 on heart failure hospitalization and management: report from a Heart Failure Unit in London during the peak of the pandemic

Reductions in Heart Failure Hospitalizations During the COVID-19 Pandemic

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This article is protected by copyright. All rights reserved.Accepted Article