Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

Baral, Ranu; Tsampasian, Vasiliki; Dębski, Maciej; Moran, Brendan; Garg, Pankaj; Clark, Allan; Vassiliou, Vassilios

doi:10.1001/jamanetworkopen.2021.3594

Cited by 111 publications

(106 citation statements)

References 77 publications

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“…Angiotensin receptor blockers (ARBs) showed a significant association with increased in-hospital mortality (Supplementary Table S4). Observational studies of renin-angiotensin-aldosterone system inhibitors and association with COVID-19 outcomes have tended to be associated with neutral to reduced risk of COVID-19 hospitalization or mortality rather than increased risk as noted in our analyses [ 37 , 38 ]. However, most of the reviewed studies were not exclusively examining a T2D population, and limited prospective evidence on this topic remains.…”

Section: Discussionmentioning

confidence: 90%

Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States

et al. 2021

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Introduction: Diabetes has been identified as a high-risk comorbidity for COVID-19 hospitalization. We evaluated additional risk factors for COVID-19 hospitalization and in-hospital mortality in a nationwide US database. Methods: This retrospective study utilized the UnitedHealth Group Clinical Discovery Database (January 1, 2019-July 15, 2020) containing de-identified nationwide administrative claims, SARS-CoV-2 laboratory test results, and COVID-19 inpatient admissions data. Logistic regression was used to understand risk factors for hospitalization and in-hospital mortality among people with type 2 diabetes (T2D) and in the overall population. Robustness of associations was further confirmed by subgroup and sensitivity analyses in the T2D population.Results: A total of 36,364 people were identified who were either SARS-CoV-2 ? or hospitalized for COVID-19. T2D was associated with increased COVID-19-related hospitalization and mortality. Factors associated with increased hospitalization risk were largely consistent in the overall population and the T2D subgroup, including age, male sex, and these top five comorbidities: dementia, metastatic tumor, congestive heart failure, paraplegia, and metabolic disease. Biguanides (mainly metformin) were consistently associated with lower odds of hospitalization, whereas sulfonylureas and insulins were associated with greater odds of hospitalization among people with T2D. Conclusion: In this nationwide US analysis, T2D was identified as an independent risk factor for COVID-19 complications. Many factors conferred similar risk of hospitalization across both populations; however, particular diabetes medications may be markers for differential risk. The insights on comorbidities and medications may inform population health initiatives, including prevention efforts for high-risk patient populations such as those with T2D.

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Section: Discussionmentioning

confidence: 90%

Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States

et al. 2021

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“…These patients tend to have positive relation with hypotension at admission and negative relation with hypertension as preexisting disease suggesting a relation between tension regulation and the level of SARS-COV2 in lungs. Recently a meta-analysis showed an association between Renin–Angiotensin–Aldosterone System inhibitors and clinical outcomes in patients with COVID-19 [ 41 ]. Activation of MHC class I antigen processing and presentation during the innate immune response implicated all components of the proteasome, but a particularly pronounced correlation was detected between levels of SARS-CoV-2 RNA and activation of components of the immunoproteasome.…”

Section: Discussionmentioning

confidence: 99%

HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease

et al. 2021

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Background The worldwide pandemic caused by the SARS-CoV-2 virus is characterized by significant and unpredictable heterogeneity in symptoms that remains poorly understood. Methods Transcriptome and single cell transcriptome of COVID19 lung were integrated with deeplearning analysis of MHC class I immunopeptidome against SARS-COV2 proteome. Results An analysis of the transcriptomes of lung samples from COVID-19 patients revealed that activation of MHC class I antigen presentation in these tissues was correlated with the amount of SARS-CoV-2 RNA present. Similarly, a positive relationship was detected in these samples between the level of SARS-CoV-2 and the expression of a genomic cluster located in the 6p21.32 region (40 kb long, inside the MHC-II cluster) that encodes constituents of the immunoproteasome. An analysis of single-cell transcriptomes of bronchoalveolar cells highlighted the activation of the immunoproteasome in CD68 + M1 macrophages of COVID-19 patients in addition to a PSMB8-based trajectory in these cells that featured an activation of defense response during mild cases of the disease, and an impairment of alveolar clearance mechanisms during severe COVID-19. By examining the binding affinity of the SARS-CoV-2 immunopeptidome with the most common HLA-A, -B, and -C alleles worldwide, we found higher numbers of stronger presenters in type A alleles and in Asian populations, which could shed light on why this disease is now less widespread in this part of the world. Conclusions HLA-dependent heterogeneity in macrophage immunoproteasome activation during lung COVID-19 disease could have implications for efforts to predict the response to HLA-dependent SARS-CoV-2 vaccines in the global population.

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“…10 Although it was initially assumed that ACE inhibitors and angiotensin receptor blockers to treat hypertension or cardiovascular conditions might exacerbate COVID-19 infection and lead to worse outcomes, the most recent available meta-analysis did not confirm this higher risk. 11 Finally, it has been suggested that modulating TMPRSS2 expression through specific antibodies or non-coding RNAs could prevent virus entry into host cells, 11 12 but these potential therapeutic options are still under investigation.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for severe outcomes in people with diabetes hospitalised for COVID-19: a cross-sectional database study

et al. 2021

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AimThis study’s objective was to assess the risk of severe in-hospital complications of patients admitted for COVID-19 and diabetes mellitus (DM).DesignThis was a cross-sectional study.SettingsWe used pseudonymised medical record data provided by six general hospitals from the HM Hospitales group in Spain.Outcome measuresMultiple logistic regression analyses were used to identify variables associated with mortality and the composite of mortality or invasive mechanical ventilation (IMV) in the overall population, and stratified for the presence or absence of DM. Spline analysis was conducted on the entire population to investigate the relationship between glucose levels at admission and outcomes.ResultsOverall, 1621 individuals without DM and 448 with DM were identified in the database. Patients with DM were on average 5.1 years older than those without. The overall in-hospital mortality was 18.6% (N=301), and was higher among patients with DM than those without (26.3% vs 11.3%; p<0.001). DM was independently associated with death, and death or IMV (OR=2.33, 95% CI: 1.7 to 3.1 and OR=2.11, 95% CI: 1.6 to 2.8, respectively; p<0.001). In subjects with DM, the only variables independently associated with both outcomes were age >65 years, male sex and pre-existing chronic kidney disease. We observed a non-linear relationship between blood glucose levels at admission and risk of in-hospital mortality and death or IMV. The highest probability for each outcome (around 50%) was at random glucose of around 550 mg/dL (30.6 mmol/L), and the risks flattened above this value.ConclusionThe results confirm the high burden associated with DM in patients hospitalised with COVID-19 infection, particularly among men, the elderly and those with impaired kidney function. Moreover, hyperglycaemia on admission was strongly associated with poor outcomes, suggesting that personalised optimisation could help to improve outcome during the hospital stay.

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Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

Cited by 111 publications

References 77 publications

Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States

Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States

HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease

Risk factors for severe outcomes in people with diabetes hospitalised for COVID-19: a cross-sectional database study

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