COVID-19—Deliberating beyond Steroids in 2021

Mahendran, AJ; Gupta, Neeraj; Gupta, Nitesh; Kumar, Rohit; Ish, Pranav

doi:10.5603/arm.a2021.0114

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…A recent systematic review of 150 studies with 33,805 patients showed that COVID-19 increased the risk of developing MACE. These complications were more frequently documented in patients with pre-existing cardiovascular comorbidities and disease severity [ 46 ]. However, a recent report by Xie et al .…”

Section: Discussionmentioning

confidence: 99%

Major adverse cardiovascular events are associated with necroptosis during severe COVID-19

et al. 2023

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Background The mechanisms used by SARS-CoV-2 to induce major adverse cardiac events (MACE) are unknown. Thus, we aimed to determine if SARS-CoV-2 can induce necrotic cell death to promote MACE in patients with severe COVID-19. Methods This observational prospective cohort study includes experiments with hamsters and human samples from patients with severe COVID-19. Cytokines and serum biomarkers were analysed in human serum. Cardiac transcriptome analyses were performed in hamsters' hearts. Results From a cohort of 70 patients, MACE was documented in 26% (18/70). Those who developed MACE had higher Log copies/mL of SARS-CoV-2, troponin-I, and pro-BNP in serum. Also, the elevation of IP-10 and a major decrease in levels of IL-17ɑ, IL-6, and IL-1rɑ were observed. No differences were found in the ability of serum antibodies to neutralise viral spike proteins in pseudoviruses from variants of concern. In hamster models, we found a stark increase in viral titters in the hearts 4 days post-infection. The cardiac transcriptome evaluation resulted in the differential expression of ~ 9% of the total transcripts. Analysis of transcriptional changes in the effectors of necroptosis (mixed lineage kinase domain-like, MLKL) and pyroptosis (gasdermin D) showed necroptosis, but not pyroptosis, to be elevated. An active form of MLKL (phosphorylated MLKL, pMLKL) was elevated in hamster hearts and, most importantly, in the serum of MACE patients. Conclusion SARS-CoV-2 identification in the systemic circulation is associated with MACE and necroptosis activity. The increased pMLKL and Troponin-I indicated the occurrence of necroptosis in the heart and suggested necroptosis effectors could serve as biomarkers and/or therapeutic targets. Trial registration Not applicable.

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Section: Discussionmentioning

confidence: 99%

Major adverse cardiovascular events are associated with necroptosis during severe COVID-19

et al. 2023

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“…To conclude, COVID-19 spread across the globe in pandemic proportions and caused huge morbidity and mortality. The sudden spurt in cases led to widespread fear, exhaustion of health-care resources and multiple treatment regimens in India 7 ; evidence-based treatment approach for treatment could hardly be realised. However, till evidence for efficacy and safety is generated, indiscriminate use of any drug should be discouraged.…”

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confidence: 99%

Newer oral antivirals for COVID-19: Are they the real game changer?

et al. 2022

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Necroptosis Drives Major Adverse Cardiovascular Events During Severe COVID-19

Wiscovitch-Russo

Ibáñez-Prada

Serrano-Mayorga

et al. 2023

Preprint

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Background The mechanisms used by SARS-CoV-2 to induce major adverse cardiac events (MACE) are unknown. Thus, we aimed to determine if SARS-CoV-2 can infect the heart to kill cardiomyocytes and induce MACE in patients with severe COVID-19. Methods This observational prospective cohort study includes experiments with hamsters and human samples from patients with severe COVID-19. Cytokines and serum biomarkers were analyzed in human serum. Cardiac transcriptome analyses were performed in hamsters' hearts. Results From a cohort of 70 patients, MACE was documented in 26% (18/70). Those who developed MACE had higher Log copies/mL of SARS-CoV-2, troponin-I, and pro-BNP in serum. Also, the elevation of IP-10 and a major decrease in levels of IL-17ɑ, IL-6, and IL-1rɑ were observed. No differences were found in the ability of serum antibodies to neutralize viral spike proteins in pseudoviruses from variants of concern. In hamster models, we found a stark increase in viral titers in the hearts 4 days post-infection. The cardiac transcriptome evaluation resulted in the differential expression of ~ 9% of the total transcripts. Analysis of transcriptional changes of the effectors of necroptosis (mixed lineage kinase domain-like, MLKL) and pyroptosis (gasdermin D) showed necroptosis, but not pyroptosis, to be elevated. Active form of MLKL (phosphorylated MLKL, pMLKL) was elevated in hamster hearts and, most importantly, in the serum of MACE patients. Conclusion SARS-CoV-2 can reach the heart during severe COVID-19 and induce necroptosis in the heart of patients with MACE. Thus, pMLKL could be used as a biomarker of cardiac damage and a therapeutic target. Trial registration: Not applicable.

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COVID-19—Deliberating beyond Steroids in 2021

Cited by 3 publications

References 7 publications

Major adverse cardiovascular events are associated with necroptosis during severe COVID-19

Major adverse cardiovascular events are associated with necroptosis during severe COVID-19

Newer oral antivirals for COVID-19: Are they the real game changer?

Necroptosis Drives Major Adverse Cardiovascular Events During Severe COVID-19

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