RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.

Background: No studies have investigated the association between self-rated health (SRH) and high-sensitivity C-reactive protein (hs-CRP) levels in South Koreans. We explored this association and analyzed differences between sexes. Methods: Using cross-sectional data from the 2015-2017 Korea National Health and Nutrition Examination Survey, we analyzed the association between SRH and high hs-CRP levels (>1.0 mg/L) in 14,544 Koreans aged ≥19 years who responded to the SRH survey and had hs-CRP test results. Differences in sociodemographic factors were analyzed using Pearson's chi-square test for categorical variables or the Mann-Whitney U test for continuous variables. Multiple logistic regression analysis was used to measure the association between hs-CRP levels and SRH according to sex while adjusting for other possible confounders. Results: The percentage of having a very poor to poor SRH was higher in the high hs-CRP level group (22.4%) than in the low hs-CRP level group (17.66%). Among men, the risk of a high hs-CRP level increased with worse SRH (adjusted for confounders; P for trend <0.001). After adjusting for all confounders, including chronic diseases, men with a very poor SRH showed a higher odds ratio (OR) for high hs-CRP levels than those with a very good SRH (fully adjusted OR, 1.74; 95% con dence interval, 1.04-2.90). Signi cant correlations were absent among women. Conclusions: A poor SRH was correlated with low-grade in ammation (high hs-CRP level) among male Korean adults. The ndings could be useful for developing health improvement programs and in goal setting at a national scale. Background Self-rated health (SRH) is an index utilized worldwide to summarize how patients perceive their overall health status [1]. SRH is an independent predictor of mortality and disease morbidity, even after adjusting for demographic, sociological, and medical risk factors [2]. Despite criticisms that SRH is assessed based on a single question, it is known to be a strong predictor in both healthy and unhealthy individuals. SRH is not only a predictor of previously diagnosed disease but also a predictor of reactions associated with the progression of disease in the premorbid stage; it encapsulates recent or sporadic health issues that may be missed by one-time objective testing, and it also re ects behavioral and emotional factors [2, 3]. C-reactive protein (CRP) is produced by hepatocytes following acute tissue injury or infection. Though CRP levels are generally elevated in cases of severe in ammation, high-sensitivity CRP (hs-CRP) levels increase nonspeci cally in the event of in ammation in the body. In particular, hs-CRP is used as an indicator to assess the risk of cardiovascular disease (CVD), and several studies have suggested hs-CRP as a predictor of mortality. In assessing CVD risk, the American Heart Association (AHA) and Centers for Disease Control and Prevention (CDC) de ned hs-CRP levels of >3.0 mg/L as indicating high risk, 1.0-3.0 mg/L as indicating average risk, and <1.0 mg/L as indicating low risk...

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG), known to regulate bone mass by inhibiting osteoclast differentiation and activation, might also play a role in vascular calcification. Increased circulating OPG levels in patients with CKD are associated with aortic calcification and increased mortality. We assessed the predictive role of OPG for all-cause and cardiovascular mortality in patients with CKD stages 3–5 over a 5-year follow-up period. We evaluated the relationship between OPG and all-cause and cardiovascular mortality in 145 CKD patients (stages 3–5) in a prospective observational follow-up study. Inflammation markers, including high-sensitivity C-reactive protein, standard echocardiography, and estimation of intima-media thickness in the common carotid artery, were assessed at baseline, and correlations with OPG levels were determined. The cutoff values for OPG were defined using ROC curves for cardiovascular mortality. Survival was assessed during follow up lasting for up to 5.5 years using Fine and Gray model. A total of 145 (89 men; age 58.9 ± 15.0 years) were followed up. The cutoff value for OPG determined using ROC was 10 pmol/L for general causes mortality and 10.08 pmol/L for CV causes mortality. Patients with higher serum OPG levels presented with higher mortality rates compared to patients with lower levels. Aalen–Johansen cumulative incidence curve analysis demonstrated significantly worse survival rates in individuals with higher baseline OPG levels for all-cause and cardiovascular mortality (p < 0.001). In multivariate analysis, OPG was a marker of general and cardiovascular mortality independent of sex, age, CVD, diabetes, and CRP levels. When CKD stages were included in the multivariate analysis, OPG was an independent marker of all-cause mortality but not cardiovascular mortality. Elevated serum OPG levels were associated with higher all-cause and cardiovascular mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD.

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to present with pulmonary and extra‐pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS‐CoV‐2 infection is likely to lead to more severe disease, with multi‐organ effects, including cardiovascular disease. SARS‐CoV‐2 has been associated with acute and long‐term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS‐CoV‐2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS‐CoV‐2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1‐like macrophage infiltration in the cardiac tissues of COVID‐19 patients. The DNA damage present in the SARS‐CoV‐2 patient samples, were further confirmed by γ‐H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon‐stimulated genes, in particular interferon and complement pathways, when compared with COVID‐19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS‐CoV‐2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra‐pulmonary organs, including the cardiovascular system of COVID‐19 patients, to delineate the immunopathobiology of SARS‐CoV‐2 infection, and long term impact on health.