Case Report: Hypercoagulopathy as a Severe Long-term Complication of Post SARS-CoV-19 Infection, Autopsy Findings in Three Patients (preprint)

Background: It has been less than two years since the advent of the COVID-19 pandemic, and there are plenty of publications describing the clinical and pathological features of this severe infectious disease, damaging not only lung but also other vital organs. However, the pathologic findings of long-term complications post virus infection have rarely been described. Case presentation: We are reporting three autopsy cases from patients who had COVID-19 one to six months before death. The patients were all SARS-CoV-2 negative at admission but expired shortly. At autopsy, the first patient showed subacute diffuse myocardial ischemic injury with microthrombi in pericardial small vessels, whereas the second patient showed catastrophic acute and subacute pulmonary infarctions with hemothorax leading to respiratory failure. The third patient showed subacute severe cerebral infarcts in the left middle cerebral artery region. Conclusions: : Our findings suggest the hypercoagulopathy and subsequent vital organ damage may persist beyond the active phase of SARS-CoV-2 infection. It is essential to evaluate and continue monitoring the COVID-19 patients after recovery, so as to identify the ones with vital organ injury in a timely manner and to take the steps to prevent severe consequence of COVID-19 complications.

A Bibliometric Analysis of 14,822 Researches on Myocardial Reperfusion Injury by Machine Learning.

Myocardial ischemia is the major cause of death worldwide, and reperfusion is the standard intervention for myocardial ischemia. However, reperfusion may cause additional damage, known as myocardial reperfusion injury, for which there is still no effective therapy. This study aims to analyze the landscape of researches concerning myocardial reperfusion injury over the past three decades by machine learning. PubMed was searched for publications from 1990 to 2020 indexed under the Medical Subject Headings (MeSH) term "myocardial reperfusion injury" on 13 April 2021. MeSH analysis and Latent Dirichlet allocation (LDA) analyses were applied to reveal research hotspots. In total, 14,822 publications were collected and analyzed in this study. MeSH analyses revealed that time factors and apoptosis were the leading terms of the pathogenesis and treatment of myocardial reperfusion injury, respectively. In LDA analyses, research topics were classified into three clusters. Complex correlations were observed between topics of different clusters, and the prognosis is the most concerned field of the researchers. In conclusion, the number of publications on myocardial reperfusion injury increases during the past three decades, which mainly focused on prognosis, mechanism, and treatment. Prognosis is the most concerned field, whereas studies on mechanism and treatment are relatively lacking.

Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart.

We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches, such as a glycocalyx mimetic, were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to-cell communication, in particular, the relevance of extracellular vesicles, such as exosomes, which transport proteins, lipids, non-coding RNAs, and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response.

The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis.

Parameters predicting COVID-19-induced myocardial injury and mortality.

Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.