Comparative Study of the Myocardium of Patients from Four COVID-19 Waves.

BACKGROUND: Few studies have compared COVID-19 patients from different waves. This study aims to conduct a clinical and morphological analysis of patients who died from COVID-19 during four waves. METHODS: The study involved 276 patients who died from COVID-19 during four waves, including 77 patients in the first wave, 119 patients in the second wave, and 78 patients in the third wave. We performed a histological examination of myocardium samples from autopsies and additionally analyzed the samples by PCR. We conducted immunohistochemistry of the myocardium for 21 samples using antibodies against CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, enteroviral VP1, and SARS-CoV-2 spike protein. We also did immunofluorescent staining of three myocardial specimens using VP1/SARS-CoV-2 antibody cocktails. Further, we ran RT-ddPCR analysis for 14 RNA samples extracted from paraffin-embedded myocardium. Electron microscopic studies of the myocardium were also performed for two samples from the fourth wave. RESULTS: Among the 276 cases, active myocarditis was diagnosed in 5% (15/276). Of these cases, 86% of samples expressed VP1, and individual cells contained SARS-CoV-2 spike protein in 22%. Immunofluorescence confirmed the co-localization of VP1 and SARS-CoV-2 spike proteins. ddPCR did not confidently detect SARS-CoV-2 RNA in the myocardium in any myocarditis cases. However, the myocardium sample from wave IV detected a sub-threshold signal of SARS-CoV-2 by qPCR, but myocarditis in this patient was not confirmed. Electron microscopy showed several single particles similar to SARS-CoV-2 virions on the surface of the endothelium of myocardial vessels. A comparison of the cardiovascular complication incidence between three waves revealed that the incidence of hemorrhage (48 vs. 24 vs. 17%), myocardial necrosis (18 vs. 11 vs. 4%), blood clots in the intramural arteries (12 vs. 7 vs. 0%), and myocarditis (19 vs. 1 vs. 6%) decreased over time, and CD8-T-killers appeared. Immunohistochemistry confirmed the presence of endotheliitis in all 21 studied cases. CONCLUSIONS: This study compared myocardial damage in patients who died during three COVID-19 waves and showed a decrease in the incidence of endotheliitis complications (thrombosis, hemorrhage, necrosis) and myocarditis over time. However, the connection between myocarditis and SARS-CoV-2 infection remains unproven.

Анализ влияния коморбидной сердечно-сосудистой патологии на течение и Ð¸ÑÑ Ð¾Ð´Ñ‹ COVID-19 у Ð³Ð¾ÑÐ¿Ð¸Ñ‚Ð°Ð»Ð¸Ð·Ð¸Ñ€Ð¾Ð²Ð°Ð½Ð½Ñ‹Ñ Ð¿Ð°Ñ†Ð¸ÐµÐ½Ñ‚Ð¾Ð² в первую и вторую волну пандемии в Евразийском регионе.

Цель:  Ð˜Ð·ÑƒÑ‡ÐµÐ½Ð¸Ðµ особенностей клинического течения новой коронавирусной инфекции и  влияния сопутствующих заболеваний на исход заболевания у госпитализированных больных с инфекцией SARS-CoV-2 в первую и вторую волны пандемии.Методы и результаты.  Для оценки особенностей течения COVID-19 в Евразийском регионе были созданы международные регистры АКТИВ 1 и во время второй волны пандемии АКТИВ 2. Набор больных в регистр АКТИВ 1 проводили с 29.06.20 по 29.10.20, набрано 5 397 пациентов. Прием пациентов на учет в АКТИВ 2 проводили с 01.11.20 до 30.03.21, набрано 2 665 больных.Результаты. Госпитальная летальность снизилась в  Ð¿ÐµÑ€Ð¸Ð¾Ð´ второй волны пандемии и  ÑÐ¾ÑÑ‚Ð°Ð²Ð¸Ð»Ð° 4,8 % против 7,6 % в  Ð¿ÐµÑ€Ð¸Ð¾Ð´ первой волны. В  Ð¿ÐµÑ€Ð¸Ð¾Ð´ второй волны пациенты были старше, имели больше сопутствующих заболеваний и поступали в стационар в более тяжелом состоянии, пациенты имели более высокий уровень полиморбидности. В период второй волны пандемии увеличилась заболеваемость бактериальной пневмонией и сепсисом, но реже встречались тромбозы глубоких вен и «Ñ†Ð¸Ñ‚Ð¾ÐºÐ¸Ð½Ð¾Ð²Ñ‹Ð¹ шторм¼. Наиболее неблагоприятными для прогноза смертности, как в первую, так и во вторую волны эпидемии были сочетания сопутствующих заболеваний: артериальная гипертензия (АГ) + хроническая сердечная недостаточность (ХСН) + сахарный диабет (СД) + ожирение, АГ + ишемическая болезнь сердца (ИБС) + ХСН + СД, АГ + ИБС + ХСН + ожирение.Заключение. Ð£ пациентов во вторую волну пандемии наблюдалось более обширное поражение ткани легких, чаще возникала фебрильная лихорадка, были выше уровни С-реактивного белка и  Ñ‚Ñ€Ð¾Ð¿Ð¾Ð½Ð¸Ð½Ð°, ниже уровни гемоглобина и лимфоцитов. Это, вероятно, связано с различной тактикой госпитализации пациентов в первую и вторую волны пандемии в странах, принявших участие в формировании регистров АКТИВ 1 и АКТИВ 2.

Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study.

BACKGROUND: Bromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection. METHODS: In a single-centre randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollment of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; and adverse events. RESULTS: The rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs. 5/25; P=0.02). CONCLUSION: Although the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or COVID-19 (ClinicalTrials.gov number, NCT04405999).

Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study.

Background and aims: Limited data exist on the cardiovascular manifestations and risk factors in people hospitalized with COVID-19 from low- and middle-income countries. This study aims to describe cardiovascular risk factors, clinical manifestations, and outcomes among patients hospitalized with COVID-19 in low, lower-middle, upper-middle- and high-income countries (LIC, LMIC, UMIC, HIC). Methods: Through a prospective cohort study, data on demographics and pre-existing conditions at hospital admission, clinical outcomes at hospital discharge (death, major adverse cardiovascular events (MACE), renal failure, neurological events, and pulmonary outcomes), 30-day vital status, and re-hospitalization were collected. Descriptive analyses and multivariable log-binomial regression models, adjusted for age, sex, ethnicity/income groups, and clinical characteristics, were performed. Results: Forty hospitals from 23 countries recruited 5,313 patients with COVID-19 (LIC = 7.1%, LMIC = 47.5%, UMIC = 19.6%, HIC = 25.7%). Mean age was 57.0 (±16.1) years, male 59.4%, pre-existing conditions included: hypertension 47.3%, diabetes 32.0%, coronary heart disease 10.9%, and heart failure 5.5%. The most frequently reported cardiovascular discharge diagnoses were cardiac arrest (5.5%), acute heart failure (3.8%), and myocardial infarction (1.6%). The rate of in-hospital deaths was 12.9% (N = 683), and post-discharge 30 days deaths was 2.6% (N = 118) (overall death rate 15.1%). The most common causes of death were respiratory failure (39.3%) and sudden cardiac death (20.0%). The predictors of overall mortality included older age (≥60 years), male sex, pre-existing coronary heart disease, renal disease, diabetes, ICU admission, oxygen therapy, and higher respiratory rates (p < 0.001 for each). Compared to Caucasians, Asians, Blacks, and Hispanics had almost 2-4 times higher risk of death. Further, patients from LIC, LMIC, UMIC versus. HIC had 2-3 times increased risk of death. Conclusions: The LIC, LMIC, and UMIC's have sparse data on COVID-19. We provide robust evidence on COVID-19 outcomes in these countries. This study can help guide future health care planning for the pandemic globally.

Correction: Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study.

[This corrects the article DOI: 10.5334/gh.1128.].

The worldwide impact of telemedicine during COVID-19: current evidence and recommendations for the future.

During the COVID-19 pandemic, telemedicine has emerged worldwide as an indispensable resource to improve the surveillance of patients, curb the spread of disease, facilitate timely identification and management of ill people, but, most importantly, guarantee the continuity of care of frail patients with multiple chronic diseases. Although during COVID-19 telemedicine has thrived, and its adoption has moved forward in many countries, important gaps still remain. Major issues to be addressed to enable large scale implementation of telemedicine include: (1) establishing adequate policies to legislate telemedicine, license healthcare operators, protect patients' privacy, and implement reimbursement plans; (2) creating and disseminating practical guidelines for the routine clinical use of telemedicine in different contexts; (3) increasing in the level of integration of telemedicine with traditional healthcare services; (4) improving healthcare professionals' and patients' awareness of and willingness to use telemedicine; and (5) overcoming inequalities among countries and population subgroups due to technological, infrastructural, and economic barriers. If all these requirements are met in the near future, remote management of patients will become an indispensable resource for the healthcare systems worldwide and will ultimately improve the management of patients and the quality of care.