COVID-19 and Cardiovascular Diseases: From Cellular Mechanisms to Clinical Manifestations.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly spread worldwide and led to over 581 million confirmed cases and over 6 million deaths as 1 August 2022. The binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor is the primary mechanism of SARS-CoV-2 infection. Not only highly expressed in the lung, ACE2 is also widely distributed in the heart, mainly in cardiomyocytes and pericytes. The strong association between COVID-19 and cardiovascular disease (CVD) has been demonstrated by increased clinical evidence. Preexisting CVD risk factors, including obesity, hypertension, and diabetes etc., increase susceptibility to COVID-19. In turn, COVID-19 exacerbates the progression of CVD, including myocardial damage, arrhythmia, acute myocarditis, heart failure, and thromboembolism. Moreover, cardiovascular risks post recovery and the vaccination-associated cardiovascular problems have become increasingly evident. To demonstrate the association between COVID-19 and CVD, this review detailly illustrated the impact of COVID-19 on different cells (cardiomyocytes, pericytes, endothelial cells, and fibroblasts) in myocardial tissue and provides an overview of the clinical manifestations of cardiovascular involvements in the pandemic. Finally, the issues related to myocardial injury post recovery, as well as vaccination-induced CVD, has also been emphasized.

Wuhan 3 years after the outbreak of the pandemic-cardiological insights and perspectives.

In November 2019, Wuhan, a city in Central China, became the center of an outbreak of pneumonia of unknown cause, which was later named "coronavirus disease 2019" (COVID-19). COVID-19 is caused by the novel severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection. The emergence of novel SARS-CoV­2 strains and mutations exerted a serious global public health threat. Although various vaccines have been developed, specific anti-SARS-CoV­2 drugs are limited. As cardiologists, we believe that because SARS-CoV­2 can bind to the angiotensin 2 receptor on the surface of cardiomyocytes, it may also lead to cardiac injury. COVID-19-associated cardiac injury is not rare in clinical practice, and most of these cases are mild, while a few might progress to fulminant myocarditis (FM). Overactivated immune response and inflammatory storm represent the core pathogenesis of COVID-19-associated FM. Early identification and diagnosis of COVID-19-associated FM are critical for its treatment. Recently, Wuhan was hit by the Omicron variant again. We proposed managing COVID-19-associated cardiac injury according to the severity, which has had a significant effect on outcome.

The potential effects of DPP-4 inhibitors on cardiovascular system in COVID-19 patients.

With the outbreak of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public healthcare systems are facing great challenges. Coronavirus disease 2019 (COVID-19) could develop into severe pneumonia, acute respiratory distress syndrome and multi-organ failure. Remarkably, in addition to the respiratory symptoms, some COVID-19 patients also suffer from cardiovascular injuries. Dipeptidyl peptidase-4 (DPP-4) is a ubiquitous glycoprotein which could act both as a cell membrane-bound protein and a soluble enzymatic protein after cleavage and release into the circulation. Despite angiotensin-converting enzyme 2 (ACE2), the recently recognized receptor of SARS-CoV and SARS-CoV-2, which facilitated their entries into the host, DPP-4 has been identified as the receptor of middle east respiratory syndrome coronavirus (MERS-CoV). In the current review, we discussed the potential roles of DPP-4 in COVID-19 and the possible effects of DPP-4 inhibitors on cardiovascular system in patients with COVID-19.

Neuraminidase inhibitor treatment is associated with decreased mortality in COVID-19 patients: a retrospective analysis.

AIMS: The aim of this study was to investigate the effects of Neuraminidase inhibitors (NI) on COVID-19 in a retrospective study. METHODS AND RESULTS: The study included an overall COVID-19 patients (n = 3267) and a 1:1 propensity score-matched patients (n = 972). The levels of plasma N-acetylneuraminic acid and neuraminidase expression were further evaluated in a panel of hospitalized and 1-month post-infection recovered COVID-19 subjects. The mortality rate in the overall patients was 9.6% (313/3267) and 9.2% (89/972) in the propensity-score matched patients. The NI treatment lowered the mortality rate (5.7% vs. 10.3%) and the critically ill conversion rate (14.1% vs. 19.7%) compare to those in the non-NI group in the overall patients and evaluated in the propensity score-matched patients when applying the multivariate Cox model for adjusting imbalanced confounding factors. Furthermore, NI treatment was associated with attenuated cytokine storm levels and acute heart injury but not liver or kidney injuries. Further analysis in a small panel of patients found the levels of N-acetylneuraminic acid and neuraminidase (dominantly the NEU3 isoform) were elevated in the hospitalized COVID-19 subjects and recovered at the 1-month post-infection stage, suggesting increasing desialylation in COVID-19 patients. CONCLUSION: These results suggest that NI treatment is associated with decreased mortality in COVID-19 subjects, especially for those subjects with acute heart injury.

Case Report: COVID-19 Vaccination Associated Fulminant Myocarditis.

Herein, we describe a novel finding of fulminant myocarditis (FM) in two subjects the day after administration of the first dose of the currently available inactivated SARS-CoV-2 vaccine (Vero cell). Cardiac magnetic resonance imaging revealed extensive myocardial edema and necrosis. A pathologic evaluation of the endocardial biopsy tissues revealed inflammatory cell (lymphocytes) infiltration and interstitial edema, myocyte necrosis, and focal areas of fibrosis. A life-support-based comprehensive treatment regimen comprising mechanical circulatory support using intra-aortic balloon pulsation and immunomodulatory therapy-glucocorticoids and intravenous immunoglobulin-was used to treat the patients with FM; eventually, the patients recovered and were discharged. To our knowledge, these are the first two reported cases of FM, with no other identified cause or associated illness, after receiving the inactivated SARS-CoV-2 vaccine (Vero cell). These findings suggest a novel pathogenesis of myocarditis which mentions to pay more attention to this rare, but lethal complication of COVID-19 vaccination.

Statin Use and In-hospital Mortality in Patients with COVID-19 and Coronary Heart Disease.

The worsening progress of coronavirus disease 2019 (COVID-19) is attributed to the proinflammatory state, leading to increased mortality. Statin works with its anti-inflammatory effects and may attenuate the worsening of COVID-19. COVID-19 patients were retrospectively enrolled from two academic hospitals in Wuhan, China, from 01/26/2020 to 03/26/2020. Adjusted in-hospital mortality was compared between the statin and the non-statin group by CHD status using multivariable Cox regression model after propensity score matching. Our study included 3133 COVID-19 patients (median age: 62y, female: 49.8%), and 404 (12.9%) received statin. Compared with the non-statin group, the statin group was older, more likely to have comorbidities but with a lower level of inflammatory markers. The Statin group also had a lower adjusted mortality risk (6.44% vs. 10.88%; adjusted hazard ratio [HR] 0.47; 95% CI, 0.29-0.77). Subgroup analysis of CHD patients showed a similar result. Propensity score matching showed an overall 87% (HR, 0.13; 95% CI, 0.05-0.36) lower risk of in-hospital mortality for statin users than nonusers. Such survival benefit of statin was obvious both among CHD and non-CHD patients (HR = 0.30 [0.09-0.98]; HR = 0.23 [0.1-0.49], respectively). Statin use was associated with reduced in-hospital mortality in COVID-19. The benefit of statin was both prominent among CHD and non-CHD patients. These findings may further reemphasize the continuation of statins in patients with CHD during the COVID-19 era.

Cardiovascular Involvement in Patients with 2019 Novel Coronavirus Disease.

2019 novel coronavirus disease (COVID-19) is caused by the infection of severe acute respiratory syndrome novel coronavirus (SARS-CoV-2). It is characterized by substantial respiratory symptoms and complicated with widespread other organ injuries. Cardiovascular impairment is one of the notable extrapulmonary manifestations, in terms of the deterioration of pre-existing cardiovascular diseases and newly onset acute events. We hereby review the high-quality reports about cardiovascular involvement in COVID-19 and summarize the main clinical characteristics of cardiac relevance for the all the first line clinical physicians. Additionally, the possible underlying mechanisms and the rationale for the application of specific medications, such as renin-angiotensin-aldosterone system inhibitors and hydroxychloroquine are also discussed.

Saving critically ill COVID-19 patients with mechanical circulatory support.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing public health crisis that has led to many deaths due to multiple organ dysfunction syndromes (MODS). This article describes the clinical characteristics, management, and outcomes of critically ill COVID-19 patients who survived the disease through mechanical circulatory support (MCS). METHODS: We studied 25 critically ill COVID-19 patients who underwent MCS from January 20, 2020, to April 10, 2020, at the Tongji Hospital of Huazhong University of Science and Technology. RESULTS: Thirteen (52%) of the 25 patients survived with MCS support, while 12 (48%) died. At the time of their hospital admission, we identified significant differences in their peak cardiac troponin I (cTnI) and interleukin 6 (IL-6) levels, as well as in their lymphocyte count and C-reactive protein (CRP) levels. Cox proportional hazards regression model revealed that receipt of renal replacement therapy (RRT) was associated with an approximately 20-fold improvement in survival [hazard ratio (HR) =0.049, 95% confidence interval (CI) =0.008 to 0.305]. The number of days spent on extracorporeal membrane oxygenation (ECMO) support and the use of hydrogen (pH) at the time of MCS was also associated with an increase in survival. This contrasted with high-sensitivity C-reactive proteins (hs-CRP) and lactate, associated with a decrease in survival during MCS. Further analysis of the determinants relating to a COVID-19 patient's chance of survival on/after MCS was also indicated by levels of IL-6 (ß=0.009, P=0.006), IL-8 (ß=0.031, P=0.020), and TNF-α (ß=0.107, P=0.014), which saw a significant increase in the 12 patients who died. This contrasts with the non-significant decrease in IL-6, IL-8, and TNF-α levels in the 13 patients who survived. CONCLUSIONS: These results indicate that pH, lactate, hs-CRP, ECMO duration, and RRT are important clinical determinants for assessing how MCS can increase the chances of critically ill COVID-19 patients surviving the disease.

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

The SARS-CoV-2 induced targeted amino acid profiling in patients at hospitalized and convalescent stage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced an ongoing global health crisis. Here we utilized a combination of targeted amino acids (AAs) and clinical biochemical profiling to analyze the plasma of coronavirus disease 2019 (COVID-19) subjects at the hospitalization stage and 1-month post-infection convalescent stage, respectively, to investigate the systematic injury during COVID-19 disease progress. We found the virus-induced inflammatory status and reduced liver synthesis capacity in hospitalized patients, which manifested with increased branched-chain AAs (BCAAs), aromatic AAs (AAAs), one-carbon related metabolites, and decreased methionine. Most of these disturbances during infection recover except for the increased levels of medium-chain acylcarnitines (ACs) in the convalescent subjects, implying the existence of incomplete fatty acids oxidation during recovery periods. Our results suggested that the imbalance of the AA profiling in COVID-19 patients. The majority of disturbed AAs recovered in 1 month. The incomplete fatty acid oxidation products suggested it might take longer time for convalescent patients to get complete recovery.

Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation caused by SARS-CoV-2.

The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

Association of glycosylated haemoglobin HbA1c levels with outcome in patients with COVID-19: A Retrospective Study.

Patients with hyperglycemia tend to be susceptible to Coronavirus disease 2019 (COVID-19). However, the association of HbA1c level with outcome of COVID-19 patients was unclear. We performed a retrospective study of 2880 cases of COVID-19 admitted in Tongji Hospital, Wuhan, China, among which 922 had detected the HbA1c levels. We found that COVID-19 patients with either lower levels of HbAlc (3%-4.9%) or higher levels of HbAlc (≥6%) were associated with elevated all-cause mortality. Meanwhile, we observed that HbAlc levels were highly correlated with haemoglobin (Hb) and total cholesterol (TC) (P < .0001), moderately correlated with albumin (ALB) and high-sensitive C reaction protein (hs-CRP) (0.0001 < P<.001), and relatively low correlated with low-density lipoprotein cholesterol (LDL-C) (.001 < P<.01). These associated cofactors might together contribute to the clinical outcome of COVID-19 patients. Furthermore, the mortality was higher in COVID-19 patients with newly diagnosed diabetes mellitus (DM) compared with COVID-19 patients with history of DM. Moreover, in patients with history of DM, the mortality was decreased in patients treated with anti-hyperglycaemic drugs. In summary, our data showed that the in-hospital mortality was increased in COVID-19 patients with lower or higher levels of HbAlc. Meanwhile, initiation of appropriate anti-hyperglycaemic treatment might improve the clinical outcome in COVID-19 patients.

Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease.

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

The Association of Low Molecular Weight Heparin Use and In-hospital Mortality Among Patients Hospitalized with COVID-19.

PURPOSE: To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients. METHODS: We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score. RESULTS: Overall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09-0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10-0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02-0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15-0.65), as well as among the elderly patients' age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level. CONCLUSIONS: Among hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.

Insulin Treatment Is Associated with Increased Mortality in Patients with COVID-19 and Type 2 Diabetes.

COVID-19 caused by SARS-COV-2 infection can lead to multi-organ injuries and significant mortality in severe and critical patients, especially among those individuals with type 2 diabetes (T2D) as a comorbidity. While attenuated mortality was observed with aggressive glucose control, it was unclear whether therapeutic regimens including insulin treatment were beneficial for patients with COVID-19 and T2D. This retrospective study investigated 689 patients with COVID-19 and T2D from a cohort of 3,305 cases from Wuhan, China. Unexpectedly, we found that insulin treatment for patients with COVID-19 and T2D was associated with a significant increase in mortality (27.2% versus 3.5%; adjusted HR, 5.38 [2.75-10.54]). Further analysis showed that insulin treatment was associated with enhanced systemic inflammation and aggravated injuries of vital organs. Therefore, insulin treatment for patients with COVID-19 and T2D should be used with caution.

Mortality and Pre-Hospitalization use of Renin-Angiotensin System Inhibitors in Hypertensive COVID-19 Patients.

Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10th to March 30th, 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15-0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non-RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non-RAS inhibitors group. The RAS inhibitors group compared with non-RAS inhibitors group had lower levels of C-reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin-6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta-analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre-hospitalization use of RAS inhibitors on mortality in hypertensive COVID-19 patients; which might be associated with reduced inflammatory response.

Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized COVID-19 patients.

BACKGROUND: Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. METHODS: We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. RESULTS: Median age was 63 years (first to third quartile 51-70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p < 0.001), with increased mortality during hospitalization (38.4% vs. 0%, p < 0.001). Among critically ill patients, non-survivors (N = 183) had a continuous increase in hs-cTnI levels during hospitalization, while survivors (N = 293) showed a decrease in hs-cTnI level between day 4 and 7 after admission. Specifically, cardiac injury is an independent marker of mortality among critically ill patients at admission, day 4-7 and 8-14. Consistent positive correlations between hs-cTnI and interleukin (IL)-6 on admission (r = 0.59), day 4-7 (r = 0.66) and day 8-14 (r = 0.61; all p < 0.001) and d-dimer (at the same timepoints r = 0.54; 0.65; 0.61, all p < 0.001) were observed. A similar behavior was observed between hs-cTnI and most of other biomarkers of inflammation and coagulation. CONCLUSIONS: Cardiac injury commonly occurs in critically ill COVID-19 patients, with increased levels of hs-cTnI beyond day 3 since admission portending a poor prognosis. A consistent positive correlation of hs-cTnI with IL-6 and d-dimer at several timepoints along hospitalization could suggest nonspecific cytokine-mediated cardiotoxicity.