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Major adverse cardiovascular events are associated with necroptosis during severe COVID-19.
Wiscovitch-Russo, Rosana; Ibáñez-Prada, Elsa D; Serrano-Mayorga, Cristian C; Sievers, Benjamin L; Engelbride, Maeve A; Padmanabhan, Surya; Tan, Gene S; Vashee, Sanjay; Bustos, Ingrid G; Pachecho, Carlos; Mendez, Lina; Dube, Peter H; Singh, Harinder; Reyes, Luis Felipe; Gonzalez-Juarbe, Norberto.
  • Wiscovitch-Russo R; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Ibáñez-Prada ED; Unisabana Center for Translational Science, Universidad de La Sabana, Chía, Colombia.
  • Serrano-Mayorga CC; Clinica Universidad de La Sabana, Chía, Colombia.
  • Sievers BL; Unisabana Center for Translational Science, Universidad de La Sabana, Chía, Colombia.
  • Engelbride MA; Clinica Universidad de La Sabana, Chía, Colombia.
  • Padmanabhan S; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Tan GS; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Vashee S; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Bustos IG; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Pachecho C; Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, 92037, USA.
  • Mendez L; Infectious Diseases and Genomic Medicine Group, J Craig Venter Institute, 9605 Medical Center Drive Suite 150, Rockville, MD, 20850, USA.
  • Dube PH; Unisabana Center for Translational Science, Universidad de La Sabana, Chía, Colombia.
  • Singh H; Unisabana Center for Translational Science, Universidad de La Sabana, Chía, Colombia.
  • Reyes LF; Clinica Universidad de La Sabana, Chía, Colombia.
  • Gonzalez-Juarbe N; Clinica Universidad de La Sabana, Chía, Colombia.
Crit Care ; 27(1): 155, 2023 04 20.
Article in English | MEDLINE | ID: covidwho-2305739
ABSTRACT

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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cardiovascular Diseases / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Crit Care Year: 2023 Document Type: Article Affiliation country: S13054-023-04423-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cardiovascular Diseases / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Crit Care Year: 2023 Document Type: Article Affiliation country: S13054-023-04423-8