Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers.

Critically ill COVID-19 patients with pleural effusion experience longer hospitalization, multisystem inflammatory syndrome, and higher rates of mortality. Generally, pleural effusion can serve as a diagnostic value to differentiate cytokine levels. This study aimed to evaluate the pleural effusions of COVID-19 deceased patients for 182 protein markers. Olink® Inflammation and Organ Damage panels were used to determine the level of 184 protein markers, e.g., ADA, BTC, CA12, CAPG, CD40, CDCP1, CXCL9, ENTPD2, Flt3L, IL-6, IL-8, LRP1, OSM, PD-L1, PTN, STX8, and VEGFA, which were raised significantly in COVID-19 deceased patients, showing over-stimulation of the immune system and ravaging cytokine storm. The rises of DPP6 and EDIL3 also indicate damage caused to arterial and cardiovascular organs. Overall, this study confirms the elevated levels of CA12, CD40, IL-6, IL-8, PD-L1, and VEGFA, proposing their potential either as biomarkers for the severity and prognosis of the disease or as targets for therapy. Particularly, this study reports upregulated ADA, BTC, DPP6, EDIL3, LIF, ENTPD2, Flt3L, and LRP1 in severe COVID-19 patients for the first time. Pearson's correlation coefficient analysis indicates the involvement of JAK/STAT pathways as a core regulator of hyperinflammation in deceased COVID-19 patients, suggesting the application of JAK inhibitors as a potential efficient treatment.

Morphological changes without histological myocarditis in hearts of COVID-19 deceased patients.

Objective. Patients with underlying heart diseases have a higher risk of dying from Covid-19. It has also been suggested that Covid-19 affects the heart through myocarditis. Despite the rapidly growing research on the management of Covid-19 associated complications, most of the ongoing research is focused on the respiratory complications of Covid-19, and little is known about the prevalence of myocarditis. Design. This study aimed to characterize myocardial involvement by using a panel of antibodies to detect hypoxic and inflammatory changes and the presence of SARS-CoV-2 proteins in heart tissues obtained during the autopsy procedure of Covid-19 deceased patients. Thirty-seven fatal COVID-19 cases and 21 controls were included in this study. Results. Overall, the Covid-19 hearts had several histopathological changes like the waviness of myocytes, fibrosis, contract band necrosis, infiltration of polymorphonuclear neutrophils, vacuolization, and necrosis of myocytes. In addition, endothelial damage and activation were detected in heart tissue. However, viral replication was not detected using RNA in situ hybridization. Also, lymphocyte infiltration, as a hallmark of myocarditis, was not seen in this study. Conclusion. No histological sign of myocarditis was detected in any of our cases; our findings are thus most congruent with the hypothesis of the presence of a circulating endothelium activating factor such as VEGF, originating outside of the heart, probably from the hypoxic part of the Covid-19 lungs.

Severe features during outbreak but low mortality observed immediately before and after a March-May 2020 COVID-19 outbreak in Stockholm, Sweden.

OBJECTIVES: The aim of this study was to estimate how well the excess mortality reflected the burden of coronavirus disease 2019 (COVID-19)-related deaths during the March-May 2020 COVID-19 outbreak in Stockholm, Sweden, and whether the excess mortality during the outbreak might have resulted in a compensatory reduced mortality after the outbreak. METHODS: Using previous 10-year or 5-year average mortality rates as a baseline, the excess mortality estimates before, during, and after the COVID-19 outbreak in March-May 2020 in Stockholm were compared. RESULTS: Weekly death estimates revealed that the immediate pre-outbreak and post-outbreak all-cause mortality did not exceed to excess mortality regardless of whether previous 10-year or 5-year average mortality was used. Forty-three days after the start of the outbreak, 74.4% of the total excess mortality was reportedly explained by known COVID-19-related deaths, and the present study reports an update, showing that 15 weeks after the start of the outbreak, the reported COVID-19-related deaths explained >99% of the total excess mortality. CONCLUSIONS: An exceptional outbreak feature of rapid excess mortality was observed. However, no excess but similarly low mortality was observed immediately prior to the outbreak and post-outbreak, thus emphasizing the severity of the first wave of the COVID-19 outbreak in Stockholm.

Estimating Total Excess Mortality During a Coronavirus Disease 2019 Outbreak in Stockholm, Sweden.

Total excess mortality peaked during a coronavirus disease 2019 (COVID-19) outbreak in Stockholm, but 25% of these deaths were not recognized as COVID-19 related nor occurred in hospitals. Estimate of total excess mortality may give a more comprehensive picture of the total disease burden during a COVID-19 outbreak, and may facilitate managing future outbreaks.

Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of COVID-19 death.

Most COVID-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was COVID-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163 + macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelium, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced COVID-19 ARDS.