Increased Prevalence of Myocardial Injury in Patients with SARS-CoV-2 Viremia

Siddiqi, Hasan K.; Weber, Brittany; Zhou, Guohai; Regan, James; Fajnzylber, Jesse; Coxen, Kendyll; Corry, Heather; Yu, Xu G.; DiCarli, Marcelo F.; Li, Jonathan Z.; Bhatt, Deepak L.

doi:10.1016/j.amjmed.2020.09.046

Cited by 19 publications

(25 citation statements)

References 13 publications

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“…Although our results show that direct infection of CMs may not be required to elicit cytotoxic effects in cardiac tissue, there is an increasing body of evidence supporting cardiomyocytes being directly infected by SARS-CoV-2 in patients with COVID-19 ( 21 , 22 , 59 ). SARS-CoV-2 can spread from lung epithelia to other organs through plasma, and viremia in COVID-19 has been closely associated with cardiac damage ( 60 ). Observing viral particles in autopsy tissue has been well documented in SARS-CoV and SARS-CoV-2 infection ( 61 , 62 ).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection of human iPSC–derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19

et al. 2021

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Although coronavirus disease 2019 (COVID-19) causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human induced pluripotent stem cell (iPSC)-derived heart cells to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural genes corroborates adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and nuclear disruption. Human autopsy specimens from patients with COVID-19 reflected similar alterations, particularly sarcomeric fragmentation. These striking cytopathic features in cardiomyocytes provide insights into SARS-CoV-2-induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise concerns about the long-term consequences of COVID-19 in asymptomatic as well as severe cases.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection of human iPSC–derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19

et al. 2021

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“…Individuals with quantifiable SARS-CoV-2 viral load at the time of ED presentation were older, had higher rates of diabetes, and had clinical laboratory values consistent with higher disease severity, including lower lymphocyte count and higher creatinine, C-reactive protein (CRP), and troponin (Table 1). Median time between symptom onset and ED presentation was 7 days (IQR [4][5][6][7][8][9][10][11] and was comparable between individuals with viral load above and below the limit of quantification (Figure 2B and Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI148635DS1). Quantified SARS-CoV-2 viral load at the time of ED presentation was correlated with older age; lower lymphocyte count; higher inflammatory markers, including CRP, D-dimer, and lactate dehydrogenase; and both renal and liver dysfunction (Figure 2C).…”

mentioning

confidence: 86%

SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes

Li¹,

Schneider²,

Mehta³

et al. 2021

Journal of Clinical Investigation

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With coronavirus disease 2019 causing over 2 million deaths globally by early 2021 (1), there remains an urgent need to elucidate disease pathogenesis to improve clinical management and treatment. There is increasing evidence that COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), frequently manifests pathology beyond the pulmonary tract (2-4). In both immunocompromised and immunocompetent hosts, SARS-CoV-2 nucleic acids have been detected across a broad range of extrapulmonary sites, including spleen, heart, liver, and intestinal tract (5-9). In addition, endothelial cells are known to express ACE2, and some reports have suggested that direct infection of endothelial cells may be leading to a hypercoagulable state with vascular and downstream organ damage. Furthermore, viremia has been implicated in transplacental transmis-BACKGROUND. SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive. METHODS.We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform. RESULTS.This study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways. CONCLUSION.These results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.

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“…For instance, troponin elevations during COVID19 hospitalizations were associated with preexisting cardiovascular morbidity, including hypertension, diabetes, chronic kidney disease, atrial fibrillation, coronary artery disease, and heart failure 135,[159][160][161] . SARS-CoV-2 viremia has also associated with higher troponin levels 162 .…”

Section: E Predictors Of Cardiovascular Involvement In Covid19mentioning

confidence: 99%