Genome-wide Association Study of Long COVID (preprint)

Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction(3-5). The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative(6,7) to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity(6), lung function(8), and cancers(9), suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.

Analysing the psychosocial and health impacts of Long COVID in Pakistan: A cross sectional study (preprint)

Long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness. The study aimed to analyze impacts of long COVID on the general health and psychosocial well-being of the Pakistani population. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychological impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). Symptoms such as decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. Majority of the participants (83.3%) had moderate level of perceived stress while moderate to severe levels of stress was observed in 17.3% of the individuals. Moreover, a high level positive mental wellbeing was also observed.

The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections (preprint)

BackgroundPoor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence causality between the chronic effects of poor sleep and respiratory infection risk. In light of the ongoing COVID-19 pandemic and potential future disease outbreaks, understanding the risk factors for these infections is of great importance. AimOur goal was to understand if chronic poor sleep could be identified as a causal risk factor for respiratory infections including influenza, upper respiratory infections and COVID-19. MethodsWe used population cohorts from the UK Biobank (N {approx} 231,000) and FinnGen (N {approx} 327,000) with ICD-10 based electronic health records and obtained diagnoses of insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital settings. We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and used summary statistics from genome-wide association studies of insomnia, influenza, URI and COVID-19 to perform Mendelian randomization analyses and assess causality. FindingsUtilizing 23 years of registry data and follow-up, we saw that insomnia diagnosis associated with increased risk for infections in FinnGen and in UK Biobank (FinnGen influenza HR = 5.32 [4.09, 6.92], P = 1.02x10-35, UK Biobank influenza HR = 1.54 [1.37, 1.73], P = 2.49x10-13). Mendelian randomization indicated that insomnia causally predisposed to influenza (OR = 1.59, P = 6.23x10-4), upper respiratory infections (OR = 1.71, P = 7.60x10-13), COVID-19 infection (OR = 1.08, P = 0.037) and risk of hospitalization from COVID-19 (OR = 1.47, P = 4.96x10-5). ConclusionsOur findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens as suggested by earlier work. As the current COVID-19 pandemic has increased the number of people suffering from poor sleep, safe interventions such as sleep management and treating individuals with insomnia could be promoted to reduce infections and save lives.