Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐19

Pan, Michael; Vasbinder, Alexi; Anderson, Elizabeth; Catalan, Toniemarie; Berlin, Hanna; Padalia, Kishan; O’Hayer, Patrick; Meloche, Chelsea; Azam, Tariq U.; Khaleel, Ibrahim; Michaud, Erinleigh; Blakely, Pennelope; Bitar, Abbas; Huang, Yiyuan; Zhao, Lili; Pop‐Busui, Rodica; Loosen, Sven H.; Chalkias, Athanasios; Tacke, Frank; Giamarellos‐Bourboulis, Evangelos J.; Reiser, Jochen; Eugen‐Olsen, Jesper; Hayek, Salim S.

doi:10.1161/jaha.121.023535

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…Some studies have shown a significant association between ACEi or ARB use and risk of SARS-CoV-2 infection and severity of health outcomes. (21, 22) In contrast to that, our study did not find any association, positive or negative, between ACEi or ARB use and serostatus. This suggests that use of ACEi or ARB may not affect vaccine efficacy, even if their use has the potential to influence risk of disease or its severity.…”

Section: Discussioncontrasting

confidence: 99%

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

Amraotkar

Bushau-Sprinkle

Keith

et al. 2022

Preprint

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Background: The impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. Methods: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated participants recruited between April 2021 through August 2021 in 18 years and older residents of Jefferson County, Kentucky, USA. Serostatus was determined by measuring SARS-CoV-2 Spike protein specific immunoglobulin (Ig) G (Spike IgG) antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. Results: Of the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) (OR=13.49; 95% CI: 4.88, 37.3; P<0.0001) and autoimmune disease (OR=11.34; 95% CI: 5.21, 24.69; P<0.0001) showed highest association with negative serostatus in fully vaccinated participants. The absence of any CHC was strongly associated with positive serostatus (OR=0.37; 95% CI: 0.19, 0.73; P=0.003). The risk of negative serostatus increased in the presence of two CHCs (OR=2.82; 95% CI: 1.14, 7) to three or more CHCs (OR=4.52; 95% CI: 1.68, 12.14). Similarly, use of 2 or more CHC related medications was significantly associated with seronegative status (OR=6.08; 95%: 2.01, 18.35). Conclusions: Presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response post-vaccination. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

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Section: Discussioncontrasting

confidence: 99%

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

Amraotkar

Bushau-Sprinkle

Keith

et al. 2022

Preprint

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“…Leisman et al and Ofosu-Barko et al reported that angiotensin-II treatment was associated with rapid improvement in multiple physiologic indices [38, 51]. The rationale for angiotensin-II therapy is based on decreasing the expression of the ACE2 receptors, which can reduce the entry of the COVID-19 virus into cells [61, 62]. However, the progressive loss of ACE2 shifts the system to an overall higher angiotensin level due to the impaired ability of ACE2 to degrade it, which may explain the initial hemodynamic stability of patients with COVID-19 [63].…”

Section: Discussionmentioning

confidence: 99%

Association of vasopressors with mortality in critically ill patients with COVID-19: A systematic review and meta-analysis

Mermiri

Mavrovounis

Laou

et al. 2022

Preprint

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Purpose: The effect of vasopressors on mortality of critically ill patients with COVID-19 has not been studied extensively. Methods: A systematic search of PubMed, Scopus, and clinicaltrials.gov was conducted for relevant articles until January 2022. Eligibility criteria were randomized controlled and non-randomized trials. The primary outcome was all-cause mortality at 28 days or 30 days. The quality of studies was assessed using the MINORS tool. Paired meta-analysis was used to estimate the pooled risk ratios along with their 95% Confidence Interval. Results: In total, 33 studies were included. Twenty-one studies with a total population of 7900 individuals provided data on mortality. Patients who received vasopressors were statistically significantly more likely to die compared to those who did not receive vasopressor therapy [RR (95%CI): 4.26 (3.15, 5.76); p<0.001]. This result remained statistically significant regardless of the in-hospital setting. In-hospital and 30-day mortality were statistically significantly higher in patients who received vasopressors [RR (95%CI): 4.60 (2.47, 8.55); p<0.001 and RR (95%CI): 2.97 (1.72, 5.14); p<0.001, respectively]. Four studies provided data on specific vasopressors; the highest mortality rate was observed in patients treated with vasopressin or epinephrine, while patients receiving angiotensin-II as a sole or second-line vasopressor agent had the lowest mortality rate. Also, analysis of 10 studies with a total population of 3519 individuals revealed that patients who received vasopressors were statistically significantly more likely to experience acute kidney injury [RR (95%CI): 3.17 (2.21, 4.54); p<0.001]. Conclusion: Vasopressors have detrimental effect on survival of critically ill patients with COVID-19.

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“… 16 , 17 An increase in suPAR levels can be triggered by various stimuli, including SARS‐CoV‐2, and suPAR is highly expressed in lung tissue, 18 which may be critical for disease progression. Indeed, suPAR has been recently implicated in the evolution of COVID‐19 and its associated complications 12 , 19 , 20 and represents the inflammatory biomarker that is most reflective of the hyperinflammatory state in patients with comorbidities. 3 , 12 , 21 …”

Section: Discussionmentioning

confidence: 99%

“…16,17 An increase in suPAR levels can be triggered by various stimuli, including SARS-CoV-2, and suPAR is highly expressed in lung tissue, 18 which may be critical for disease progression. Indeed, suPAR has been recently implicated in the evolution of COVID-19 and its associated complications 12,19,20 and represents the inflammatory biomarker that is most reflective of the hyperinflammatory state in patients with comorbidities. 3,12,21 The WHO-CPS score was developed in response to the needs of the rapidly evolving COVID-19 outbreak, including a measure of viral burden, a measure of patient survival, and a measure of patient progression.…”

Section: Discussionmentioning

confidence: 99%

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Papagiannakis

Tourlakopoulos

Pagonis

et al. 2022

Eur J Clin Investigation

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Background COVID‐19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID‐19. Methods The primary outcome measure in this international, multi‐centre, prospective, observational study with adult patients hospitalized primarily for COVID‐19 was the association of WHO Clinical Progression Scale (WHO‐CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin‐6. Admission plasma suPAR levels were determined using the suPARnostic ® ELISA and suPARnostic ® Turbilatex assays. Results Seven hundred and sixty‐seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log‐suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point ( p < .001). All the other markers were also correlated with WHO‐CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47–3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO‐CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759–0.836). Conclusions suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

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Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐19

Cited by 21 publications

References 37 publications

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

Association of vasopressors with mortality in critically ill patients with COVID-19: A systematic review and meta-analysis

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

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