Assessment of cardiovascular & pulmonary pathobiology in vivo during acute COVID-19 (preprint)

Importance: Acute COVID19 related myocardial, pulmonary and vascular pathology, and how these relate to each other, remains unclear. No studies have used complementary imaging techniques, including molecular imaging, to elucidate this. Objective: We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID19. Design, Setting and Participants: Consecutive patients presenting with acute COVID19 were recruited during hospital admission in a prospective cross sectional study. Imaging involved computed tomography coronary angiography (CTCA - identified coronary disease), cardiac 2deoxy2[fluorine18]fluoroDglucose positron emission tomography/computed tomography (18F FDG PET/CT identified vascular, cardiac and pulmonary inflammatory cell infiltration) and cardiac magnetic resonance (CMR identified myocardial disease), alongside biomarker sampling. Results: Of 33 patients (median age 51 years, 94% male), 24 (73%) had respiratory symptoms, with the remainder having non-specific viral symptoms. Nine patients (35%, n=9/25) had CMR defined myocarditis. 53% (n=5/8) of these patients had myocardial inflammatory cell infiltration. Two patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with myocarditis (8.4ng/L [IQR 4.0, 55.3] vs 3.5ng/L [2.5, 5.5], p=0.07) or myocardial cell infiltration (4.4ng/L [3.4, 8.3] vs 3.5ng/L [2.8, 7.2], p=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR 5, 31%) and 11% (7, 18%) respectively. Neither were associated with presence of myocarditis. Conclusions and relevance: Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is non-ischaemic, and not due to a vasculitic process.

Risk of hospitalisation with coronavirus disease 2019 in healthcare workers and their households:a nationwide linkage cohort study (preprint)

ObjectiveMany healthcare staff work in high-risk settings for contracting and transmitting Severe Acute Respiratory Syndrome Coronavirus 2. Their risk of hospitalisation for coronavirus disease 2019 (COVID-19), and that of their households, is poorly understood. Design and settings and participantsDuring the peak period for COVID-19 infection in Scotland (1st March 2020 to 6th June 2020) we conducted a national record linkage study to compare the risk of COVID-19 hospitalisation among healthcare workers (age: 18-65 years), their households and other members of the general population. Main outcomeHospitalisation with COVID-19 ResultsThe cohort comprised 158,445 healthcare workers, the majority being patient facing (90,733 / 158,445; 57.3%), and 229,905 household members. Of all COVID-19 hospitalisations in the working age population (18-65-year-old), 17.2% (360 / 2,097) were in healthcare workers or their households. Adjusting for age, sex, ethnicity, socio-economic deprivation and comorbidity, the risk of COVID-19 hospitalisation in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazards ratio [HR] 0.81; 95%CI 0.52-1.26 and 0.86; 95%CI 0.49-1.51 respectively). In models adjusting for the same covariates however, patient facing healthcare workers, compared to non-patient facing healthcare workers, were at higher risk (HR 3.30; 95%CI 2.13-5.13); so too were household members of patient facing healthcare workers (HR 1.79; 95%CI 1.10-2.91). On sub-dividing patient-facing healthcare workers into those who worked in front-door, intensive care and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (HR 2.09; 95%CI 1.49-2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of COVID-19 hospitalisation was less than 0.5% but was 1% and above in older men with comorbidity. ConclusionsHealthcare workers and their households contribute a sixth of hospitalised COVID-19 cases. Whilst the absolute risk of hospitalisation was low overall, patient facing healthcare workers and their households had 3- and 2-fold increased risks of COVID-19 hospitalisation.

Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. (preprint)

Background: Cardiovascular diseases(CVD) increase mortality risk from coronavirus infection(COVID-19), but there are concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both direct, through infection, and indirect, through changes in healthcare. Methods: We used population-based electronic health records from 3,862,012 individuals in England to estimate pre- and post-COVID-19 mortality risk(direct effect) for people with incident and prevalent CVD. We incorporated: (i)pre-COVID-19 risk by age, sex and comorbidities, (ii)estimated population COVID-19 prevalence, and (iii)estimated relative impact of COVID-19 on mortality(relative risk, RR: 1.5, 2.0 and 3.0). For indirect effects, we analysed weekly mortality and emergency department data for England/Wales and monthly hospital data from England(n=2), China(n=5) and Italy(n=1) for CVD referral, diagnosis and treatment until 1 May 2020. Findings: CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy and England during the pandemic. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown, and is still reduced in Italy and England. Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous(peak RR 1.4). For total CVD(incident and prevalent), at 10% population COVID-19 rate, we estimated direct impact of 31,205 and 62,410 excess deaths in England at RR 1.5 and 2.0 respectively, and indirect effect of 49932 to 99865 excess deaths. Interpretation: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the COVID-19 pandemic.