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Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled
Behrooz Heydari1, Adeleh Sahebnasagh2, Mohammad Ali Omrani3
1Department of Clinical Pharmacy, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Objective:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients.
Methods:
We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model.
Results:
Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242).
Conclusion:
CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.
Insights
Calcineurin inhibitors (CIs) show potential in treating COVID-19 by reducing mortality rates. While CIs inhibit viral replication, they did not significantly increase hospital discharge rates in this systematic review.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing COVID-19, leads to severe multi-organ failure and mortality.
- Vascular Endothelial Growth Factor (VEGF) plays a role in the pathophysiology of COVID-19.
- Calcineurin inhibitors (CIs) are known immunosuppressants with potential anti-VEGF properties.
Purpose of the Study:
- To systematically review the literature on the efficacy of calcineurin inhibitors (CIs) as anti-VEGF agents in COVID-19 patients.
- To evaluate the impact of CIs on clinical outcomes, including mortality and hospital discharge rates.
- To assess the potential therapeutic role of CIs in managing SARS-CoV-2 infection.
Main Methods:
- Systematic literature search across major databases (PubMed, Scopus, Web of Science, Google Scholar, Cochrane, ClinicalTrials.gov) from December 2019 to February 2023.
- Quality assessment of included controlled trials using the Cochrane Collaboration tool.
- Meta-analysis of data from three trials (293 participants) using Comprehensive Meta-Analysis Software and a random-effects model.
Main Results:
- Calcineurin inhibitors (CIs) significantly reduced the mortality rate in COVID-19 patients (RR: 0.598, P=0.010) with low statistical heterogeneity.
- Analysis of two studies (84 patients) indicated that CIs did not significantly increase the rate of hospital discharge (RR: 1.161, P=0.485).
- Low heterogeneity was observed for both mortality and hospital discharge outcomes.
Conclusions:
- Calcineurin inhibitors (CIs) demonstrate a potential therapeutic benefit for COVID-19 patients by inhibiting viral replication.
- CIs can prevent SARS-CoV-2 nucleocapsid protein activity, thus mitigating respiratory tract tissue damage.
- Further research may solidify the role of CIs in COVID-19 treatment strategies.
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