Cardiovascular manifestations in COVID-19 patients: A systematic review and meta-analysis.

Since December 2019, the COVID-19 pandemic has affected the global population, and one of the major causes of mortality in infected patients is cardiovascular diseases (CVDs).For this systematic review and meta-analysis, we systematically searched Google Scholar, Scopus, PubMed, Web of Science, and Cochrane databases for all articles published by April 2, 2020. Observational studies (cohort and cross-sectional designs) were included in this meta-analysis if they reported at least one of the related cardiovascular symptoms or laboratory findings in COVID-19 patients. Furthermore, we did not use any language, age, diagnostic COVID-19 criteria, and hospitalization criteria restrictions. The following keywords alone or in combination with OR and AND operators were used for searching the literature: "Wuhan coronavirus", "COVID-19", "coronavirus disease 2019", "SARS-CoV-2", "2019 novel coronavirus" "cardiovascular disease", "CVD", "hypertension", "systolic pressure", "dyspnea", "hemoptysis", and "arrhythmia". Study characteristics, exposure history, laboratory findings, clinical manifestations, and comorbidities were extracted from the retrieved articles. Sixteen studies were selected which involved 4754 patients, including 2103 female and 2639 male patients. Among clinical cardiac manifestations, chest pain and arrhythmia were found to have the highest incidence proportion. In addition, elevated lactate dehydrogenase (LDH) and D-dimer levels were the most common cardiovascular laboratory findings. Finally, hypertension, chronic heart failure, and coronary heart disease were the most frequently reported comorbidities. The findings suggest that COVID-19 can cause various cardiovascular symptoms and laboratory findings. It is also worth noting that cardiovascular comorbidities like hypertension have a notable prevalence among COVID-19 patients.

Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNß compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNß1a and IFNß1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNß1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNß1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNß1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10-5.17, P-value = 0.031) while the IFNß1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63-3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNß1a group and 30% in the IFNß1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNß1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19.

BACKGROUND: The scientific evidence concerning pathogenesis and immunopathology of the coronavirus disease 2019 (COVID-19) is rapidly evolving in the literature. To evaluate the different tissues obtained by biopsy and autopsy from five patients who expired from severe COVID-19 in our medical center. METHODS: This retrospective study reviewed five patients with severe COVID-19, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and imaging, to determine the potential correlations between histologic findings with patient outcome. RESULTS: Diffuse alveolar damage (DAD) and micro-thrombosis were the most common histologic finding in the lung tissues (4 of 5 cases), and immunohistochemical (IHC) findings (3 of 4 cases) suggested perivascular aggregation and diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes. Two of five cases had mild predominantly perivascular lymphocytic infiltration, single cell myocardial necrosis and variable interstitial edema in myocardial samples. Hypertrophic cardiac myocytes, representing hypertensive cardiomyopathy was seen in one patient and CD4+ and CD8+ T lymphocytes were detected on IHC in two cases. In renal samples, acute tubular necrosis was observed in 3 of 5 cases, while chronic tubulointerstitial nephritis, crescent formation and small vessel fibrin thrombi were observed in 1 of 5 samples. Sinusoidal dilation, mild to moderate chronic portal inflammation and mild mixed macro- and micro-vesicular steatosis were detected in all liver samples. CONCLUSION: Our observations suggest that clinical pathology findings on autopsy tissue samples could shed more light on the pathogenesis, and consequently the management, of patients with severe COVID-19.