Can sartans improve clinical outcomes in hypertensive patients with COVID-19?

Influencing RAS Activity in COVID-19

Currently, there is still no specific and effective treatment for COVID-19. The risk of severe course is especially prevalent among older individuals with cardiovascular (CV) diseases, including hypertension. RAS plays an important role in regulating electrolyte balance and blood pressure, involving two pathways [ACE/Ang II/AT₁R and ACE2/Ang (1–7)/Mas], which are in dynamic equilibrium under physiological conditions.

It is hypothesized that the SARS-CoV-2 virus, similar to SARS, penetrates the host cell through the ACE2 receptor. Reduced ACE2 expression due to SARS infection leads to an imbalance between the ACE/Ang II/AT₁R axis and the ACE2/Ang (1–7)/Mas axis. Targeting the ACE/Ang II/AT₁R axis represents a therapeutic strategy for treating hypertension using RASi. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are used.

It is still unclear whether RASi treatment affects clinical outcomes in patients with COVID-19. Therefore, Chinese doctors conducted a retrospective analysis of medical records of COVID-19 patients admitted to the Third People's Hospital of Shenzhen from January 11 to February 23, 2020.

Retrospectively Evaluated Population

417 patients were admitted. Hypertension was found in 51 (12.23%) individuals. Nine (17.6%) patients who did not use any antihypertensives during hospitalization were excluded from further analysis. The remaining 42 (82.4%) were divided into 2 groups based on the medication used: 17 patients used ACEi or ARBs (ACEi/ARBs group), and 25 patients were treated with other antihypertensives. There were no significant differences in the degree of hypertension between the two groups. Comorbidities (type 2 diabetes mellitus or coronary artery disease) were noted in 8 (32%) patients in the group without ACEi/ARBs and 5 (29.41%) in the ACEi/ARBs group.

The aim of the analysis was to compare clinical, inflammatory, immunological, and viral findings in both groups.

Findings

Disease Course During Hospitalization

More severe cases occurred in the group treated with antihypertensives other than ACEi/ARBs compared to the group treated with ACEi/ARBs. In the subgroup with severe symptoms, there were 12 (48%) patients from the group without ACEi/ARBs, with 1 patient dying. In the ACEi/ARBs group, only 4 (23.5%) patients had severe cases, and none died.

Laboratory Findings

A trend towards lower levels of the cytokine IL-6 in peripheral blood was observed in the ACEi/ARBs group. There was a significant increase in the absolute number of CD3⁺ and CD8⁺ T lymphocytes compared to the group without ACEi/ARBs. No differences were observed in the number of CD4⁺ T cells. The groups did not differ significantly in C-reactive protein (CRP) levels.

Viral Load

Both groups were admitted to the hospital with the same viral load. During hospitalization, the maximum viral load was significantly lower in the group treated with ACEi/ARBs compared to the group using other antihypertensives.

Conclusion

This is the first clinical evidence that RAS inhibitors improve clinical outcomes in hypertensive patients infected with the SARS-CoV-2 coronavirus. The analysis suggests that these patients may benefit from persistent or preferential use of ACEi or ARBs. These drug groups regulate immune functions and inhibit inflammatory responses through an unknown mechanism, which needs to be clarified by further in vitro and in vivo studies.

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Source: Meng J., Xiao G., Zhang J. et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect 2020; 9 (1): 757–760, doi: 10.1080/22221751.2020.1746200.