Natural history of long-COVID in a nationwide, population cohort study (preprint)

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to adults never infected. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health: 26 symptoms and health-related quality of life, six, 12 and 18 months after the index test. Those previously infected also self-reported current recovery status (fully, partially or not recovered). Here we show that, of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection than among those never infected. Whilst resolution of some symptoms of long-COVID (altered taste/smell and confusion) is reassuring, late onset cough and hearing problems in some individuals merits further investigation.

Long-COVID in Scotland Study: a nationwide, population cohort study (preprint)

BACKGROUNDWith increasing numbers of people infected with SARS-CoV-2, a better understanding of long-COVID is required to inform health and social care support.METHODSA nationwide, ambidirectional, population cohort was constructed of adults in Scotland with a positive SARS-CoV-2 PCR test from April 2020 to May 2021 and a matched, never infected comparison group. Recovery status, symptoms, quality of life, impaired daily activities, hospitalization and death were ascertained via repeated self-completed questionnaires, at 6, 12 and 18-months follow-up, and linkage to hospitalization and death records.RESULTSThe cohort comprised 31,486 symptomatic and 1,795 asymptomatic infected individuals, and 62,957 never infected individuals. Of the former, 1,856 (6%) had not recovered and 13,350 (42%) only partially. Lack of recovery was associated with severe (hospitalized) infection, older age, female sex, deprivation, respiratory disease, depression and multimorbidity. Twenty-four persistent symptoms were independently associated with previous infection including breathlessness (OR 3.44, 95% CI 3.29–3.59), palpitations (OR 2.51, OR 2.37–2.67), chest pain (OR 2.10, 95% CI 1.97–2.24), and confusion (OR 2.93, 95% CI 2.78–3.08). Pre-infection vaccination was associated with reduced risk of seven symptoms. Previous symptomatic infection was also associated with poorer quality of life (EQ-5D median 75 vs 80, p < 0.001) and impairment across all daily activities. Asymptomatic infection was not associated with adverse outcomes.CONCLUSIONSThe sequelae of SARS-CoV-2 infection are wide-ranging and not explained by confounding. The risk of long-COVID is greater following severe infections requiring hospitalization and absent following asymptomatic infection, whilst pre-infection vaccination may be protective.

Risk of myocarditis following sequential COVID-19 vaccinations by age and sex (preprint)

ABSTRACT In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy. Funding Health Data Research UK.

The 4C Initiative (Clinical Care for Cardiovascular disease in the COVID-19 pandemic): monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases in the UK (preprint)

Background: The coronavirus (COVID-19) pandemic affects cardiovascular diseases (CVDs) directly through infection and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects. Methods: We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs (acute coronary syndromes, heart failure, stroke and transient ischaemic attack, venous thromboembolism, peripheral arterial disease and aortic aneurysm) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. Findings: Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. Interpretation: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.