Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (Covid-19)

Mehta N, Kalra A, Nowacki AS et al 

JAMA Cardiol 2020, May 5  doi:10.1001/jamacardio.2020.1855 [Published online]

The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the Covid-19 pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use.

This study examined the association between the use of ACEIs/ARBs with the likelihood of testing positive for Covid-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of Covid-19 (eg. hospitalisation, intensive care unit admission and requirement for mechanical ventilation).

This retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. It included all patients tested for Covid-19 between March 8 and April 12, 2020 with a history of taking ACEIs or ARBs at the time of Covid-19 testing.

A total of 18,472 patients were tested for Covid-19. The mean (SD) age was 49 (21) years, 7,384 (40%) were male, and 12,725 (69%) were white. Of 18,472 patients who underwent Covid-19 testing, 2,285 (12.4%) were taking either ACEIs or ARBs. A positive Covid-19 test result was observed in 1,735 of 18, 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with Covid-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95%CI, 0.81 to 1.15).

In conclusion, this study found no association between ACEI or ARB use and Covid-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the Covid-19 pandemic. However, further study in larger numbers of hospitalised patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of Covid-19 severity.

Association of hypertension and antihypertensive treatment with Covid-19 mortality: a retrospective observational study 

Gao C, Cai Y, Zhang K et al 

Eur Heart J 2020, June 4;  ehaa433   doi: 10.1093/eurheartj/ehaa433 [Online ahead of print]

It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with Covid-19.

This is a retrospective observational study of all patients admitted with Covid-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of Covid-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. 

Among 2,877 hospitalised patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% versus 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17 to 3.82, p = 0.013].

 Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% versus 3.2%, adjusted HR 2.17, 95% CI 1.03 to 4.57, p = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% versus 3.6%, adjusted HR 0.85, 95% CI 0.28 to 2.58, p = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45 to 0.94, p = 0.20).

While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, the authors did not detect any harm of RAAS inhibitors in patients infected with Covid-19. However, the results should be considered as exploratory and interpreted cautiously.

Diagnosis, prevention and treatment of thromboembolic complications in Covid-19: Report of the National Institute for Public Health of the Netherlands

Oudkerk M, Büller HR, Kuijpers D et al

Report of the National Institute for Public Health of the Netherlands. Radiology, 2020, Apr 23; 201629
doi: 10.1148/radiol.2020201629

A potential link between mortality, D-dimer values and a prothrombotic syndrome has been reported in patients with Covid-19 infection. The National Institute for Public Health of the Netherlands asked a group of Radiology and Vascular Medicine experts to provide guidance for the imaging workup and treatment of these important complications. This report summarises evidence for thromboembolic disease, potential diagnostic and preventive actions as well as recommendations for patients with Covid-19 infection.

Summary recommendations from the report: 

Prophylactic-dose low-molecular-weight heparin should be initiated in all patients with (suspected) Covid-19 admitted to the hospital, irrespective of risk scores (eg. Padua score)

A baseline (non-contrast) chest CT should be considered in all patients with suspected Covid-19 who have an indication for hospital admission (Dutch Healthcare)

In patients with suspected Covid-19 as well as a high clinical suspicion for pulmonary embolism (eg. based on haemoptysis, unexplained tachycardia or signs/symptoms of deep vein thrombosis, acute deterioration on moving patient), CT pulmonary angiography should be considered if the D-dimer level is elevated. The D-dimer threshold used should follow locally used algorithms, ie. ≥ 500mg/L, age-adjusted threshold, or ≥ 1,000mg/L when no YEARS criteria are present. If PE is confirmed, therapeutic anticoagulation is indicated

In patients with Covid-19 admitted to hospital, routine D-dimer testing on admission and serially during hospital stay should be considered for prognostic stratification with additional imaging as available at local level:

a. In patients with a D-dimer < 1,000µg/L on admission and no significant increase during follow-up, prophylactic anticoagulation should be continued

b. In patients with a D-dimer < 1,000µg/L on admission but a significant increase during hospital stay to levels > 2,000-4,000µg/L, imaging for DVT or PE should be considered, in particular when signs suggestive of clinically-relevant hypercoagulability such as venous congestion/thrombosis are present on chest CT, clotting of extracorporeal circuits, or when patients deteriorate clinically (eg. refractory hypoxemia or unexplained new-onset tachycardia or hypotension). When imaging is not feasible, therapeutic-dose low-molecular weight heparin without imaging can be considered when the risk of bleeding is acceptable

c. For patients with D-dimer values of 1,000 to 2,000µg/L, there is no clear-cut guidance other than institution of prophylactic anticoagulation. These patients may suffer from venous thromboembolism and where possible this should be excluded. Close monitoring of D-dimer in combination with clinical findings should lead to further decision making along the lines of low versus strongly increased D-dimer levels

d. In patients with a strongly increased D-dimer on admission (eg. 2,000 to 4,000µg/L), caution is warranted. D-dimer testing should be repeated within 24 to 48 hours to detect further increases, in which case imaging for DVT or PE should be considered as outlined above.

Conscious proning: an introduction of a proning protocol for non-intubated, awake, hypoxic emergency department Covid-19 patients

Jiang LG, LeBaron J, Bodnar D et al

Acad Emerg Med 2020, May 27   doi: 10.1111/acem.14035 [Online ahead of print]

A major cause of morbidity and mortality due to Covid-19 has been the worsening hypoxia which, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, as it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. The authors created a system-wide multi-institutional (New York-Presbyterian Hospital enterprise) protocol for placing awake, non-intubated, emergency department patients with suspected or confirmed Covid-19 in the prone position. In this piece, they describe the background literature and the approach they have taken at the institution as they care for a high burden of Covid-19 cases with respiratory symptoms.