Background There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. Methods We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. Results We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 – 0.77]). Conclusion An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.

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IntroductionThe COVID-19 pandemic is ongoing, yet, due to the lack of a COVID-19-specific tool, clinicians must use pre-existing illness severity scores for initial prognostication. However, the validity of such scores in COVID-19 is unknown.MethodsThe North West Collaborative Organisation for Respiratory Research performed a multicentre prospective evaluation of adult patients admitted to the hospital with confirmed COVID-19 during a 2-week period in April 2020. Clinical variables measured as part of usual care at presentation to the hospital were recorded, including the Confusion, Urea, Respiratory Rate, Blood Pressure and Age Above or Below 65 Years (CURB-65), National Early Warning Score 2 (NEWS2) and Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) scores. The primary outcome of interest was 30-day mortality.ResultsData were collected for 830 people with COVID-19 admitted across seven hospitals. By 30 days, a total of 300 (36.1%) had died and 142 (17.1%) had been in the intensive care unit. All scores underestimated mortality compared with pre-COVID-19 cohorts, and overall prognostic performance was generally poor. Among the ‘low-risk’ categories (CURB-65 score<2, NEWS2<5 and qSOFA score<2), 30-day mortality was 16.7%, 32.9% and 21.4%, respectively. NEWS2≥5 had a negative predictive value of 98% for early mortality. Multivariable logistic regression identified features of respiratory compromise rather than circulatory collapse as most relevant prognostic variables.ConclusionIn the setting of COVID-19, existing prognostic scores underestimated risk. The design of new prognostic tools should focus on features of respiratory compromise rather than circulatory collapse. We provide a baseline set of variables which are relevant to COVID-19 outcomes and may be used as a basis for developing a bespoke COVID-19 prognostication tool.

Type II alveolar epithelial cell (AEC) apoptosis is a prominent feature of fibrotic lung diseases and animal models of pulmonary fibrosis. While there is growing recognition of the importance of AEC injury and apoptosis as a causal factor in fibrosis, the underlying mechanisms that link these processes remain unknown. We have previously shown that targeting the type II alveolar epithelium for injury by repetitively administering diphtheria toxin to transgenic mice expressing the diphtheria toxin receptor off of the surfactant protein C promoter (SPC-DTR) develop lung fibrosis, confirming that AEC injury is sufficient to cause fibrosis. In the present study, we find that SPC-DTR mice develop increased activation of caspase 3/7 after initiation of diphtheria toxin treatment consistent with apoptosis within AECs. We also find evidence of efferocytosis, the uptake of apoptotic cells, by alveolar macrophages in this model. To determine the importance of efferocytosis in lung fibrosis, we treated cultured alveolar macrophages with apoptotic type II AECs and found that the uptake induced pro-fibrotic gene expression. We also found that the repetitive intrapulmonary administration of apoptotic type II AEC or MLE-12 cells induces lung fibrosis. Finally, mice lacking a key efferocytosis receptor, CD36, developed attenuated fibrosis in response to apoptotic MLE-12 cells. Collectively, these studies support a novel mechanism linking AEC apoptosis with macrophage pro-fibrotic activation via efferocytosis and reveal previously unrecognized therapeutic targets.

Background COVID-19 caused by severe acute respiratory syndrome coronavirus 2 most commonly manifests with fever and respiratory illness. The cardiovascular manifestations have become more prevalent but can potentially go unrecognized. We look to describe cardiac manifestations in three patients with COVID-19 using cardiac enzymes, electrocardiograms, and echocardiography. Case summaries The first patient, a 67-year-old Caucasian female with non-ischaemic dilated cardiomyopathy, presented with dyspnoea on exertion and orthopnoea 1 week after testing positive for COVID-19. Echocardiogram revealed large pericardial effusion with findings consistent with tamponade. A pericardial drain was placed, and fluid studies were consistent with viral pericarditis, treated with colchicine, hydroxychloroquine, and methylprednisolone. Follow-up echocardiograms showed apical hypokinesis, that later resolved, consistent with Takotsubo syndrome. The second patient, a 46-year-old African American male with obesity and type 2 diabetes mellitus presented with fevers, cough, and dyspnoea due to COVID-19. Clinical course was complicated with pulseless electrical activity arrest; he was found to have D-dimer and troponin elevation, and inferior wall ST elevation on ECG concerning for STEMI due to microemboli. The patient succumbed to the illness. The third patient, a 76-year-old African American female with hypertension, presented with diarrhoea, fever, and myalgia, and was found to be COVID-19 positive. Clinical course was complicated, with acute troponin elevation, decreased cardiac index, and severe hypokinesis of the basilar wall suggestive of reverse Takotsubo syndrome. The cardiac index improved after pronation and non-STEMI therapy; however, the patient expired due to worsening respiratory status. Discussion These case reports demonstrate cardiovascular manifestations of COVID-19 that required monitoring and urgent intervention.