ABSTRACT
Background: Systemic hyperinflammation is key to the pathogenesis of severe, acute COVID-19. However, few studies have analysed inflammatory profiles in adults with mild/moderate COVID-19, or in those with post-acute sequelae of COVID-19 (PASC). We aimed to i) describe trajectories of cytokines in a prospective cohort of adults with mild to severe COVID-19, compared to uninfected, healthy controls and ii) identify early (< 4 weeks after illness onset onset) predictors of ongoing PASC and inflammation at 6 months after illness onset. Method(s): RECoVERED is a prospective cohort of adults with laboratoryconfirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24. Participants completed monthly symptom questionnaires. PASC was defined as having at least one ongoing symptom that originated < 1 month of illness onset. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We performed random forest regression to identify early predictors of PASC and raised CRP/IL-6 at 24 weeks, using Shapley additive explanation values as measures of importance for the different predictors. Result(s): Of 349 RECoVERED participants, 186 (53%) had >=2 serum samples and were included in current analyses. Of these, 101 (54%: 45/101 [45%] female, median age 55 years [IQR=45-64]) reported PASC at 12 weeks after illness onset, of whom none recovered by 24 weeks. We included 37 uninfected controls (17/37 [46%] female, median age 49 years [IQR=40-56]). At 4 weeks after illness onset, levels of IP10, IL10, IL17, IL1beta, IL6 and TNFalpha were significantly elevated among participants infected with SARS-CoV-2 compared to controls. Ongoing PASC was independently associated with raised CRP at 24 weeks. Early raised IL1beta and sCD14 levels and greater BMI at illness onset were the strongest predictors of PASC at 24 weeks. Those with higher early sCD14 or IL1beta and TNFalpha levels were also more likely to have persistently raised CRP and IL6, respectively, at 24 weeks (Fig.1). Conclusion(s): Differences in cytokine concentrations between individuals with COVID-19 and uninfected controls largely were greatest < 4 weeks after illness onset. In our study, ongoing PASC was associated with persistently elevated CRP at 24 weeks. Early immune dysregulation was, alongside BMI, an important determinant for persistent PASC. Further investigation of individuals with PASC and long-term aberrant cytokine levels may help improve our understanding of the condition. (Figure Presented).
ABSTRACT
Background: Myocarditis without myositis has been described following mRNA SARS-CoV-2 vaccination. The literature on post-vaccine antibody mediated myositis is limited and to date no case series have been reported with a distinct clinical syndrome and a single myositis specific antibody, related to SARS-CoV-2 mRNA vaccination or COVID-19. Over a 6-month period in 2021, 54 patients were referred to our tertiary referral centre for suspected myositis. Out of 25 patients with a diagnosis of myositis, we identified three patients with a distinct clinical syndrome with myositis and myocarditis with anti-Jo-1 antibodies, following SARS-CoV-2 mRNA vaccination (BNT162-Pfizer-BioNtech;n=2) or following a mild COVID-19 infection (n=1). Results: Three patients (one woman, two men;49, 50 and 58 years old) developed progressive muscle weakness and muscle pain following either vaccination (patient 1 and 2) or mild COVID-19 infection (patient 3). Patients 2 and 3 had a history of anti- CCP positive rheumatoid arthritis (RA), which had been untreated for three years in patient 2. Both post-vaccine cases had severe pitting edema of the legs, patient 2 also had arthritis. None of the patients had mechanic's hands, Raynaud's phenomenon, or interstitial lung disease (ILD). The time interval between the SARS-CoV-2 trigger and the onset of progressive muscle weakness was between 10 and 14 days (patient 1 and 3) and was estimated cybetween three and seven days in patient 2. Laboratory tests showed highly elevated CK levels (17-32 times upper limit of normal (ULN)) and troponine T levels (14-34 times ULN). In patient 2, in addition, troponin I was tested (42 times ULN), which is more specific for myocardial involvement. In patient 1 supraventricular tachycardia, unspecific ST- and Twave abnormalities and elevated NTproBNP were found. In all patients, testing for myositis specific antibodies (MSAs;EUROline myositis 16 Ag. lineblot assay) showed anti-Jo-1 antibodies (semi-quantitatively in the highest possible range). Muscle MRI showed widespread muscle edema in all patients and extensive fascial and subcutaneous edema in the legs in the post-vaccine cases (figure 1). Muscle biopsies showed inflammatory myopathy. Cardiac MRI showed abnormalities in all patients: Pericardial effusion and/or late contrast enhancement of the epicardial myocardium (figure 1). All patients showed major improvement in response to immunosuppressive therapy and could discontinue highdosed steroids after three and six months. Discussion: In conclusion, we report three patients with a distinct clinical picture of anti-Jo-1 myositis and myocarditis without ILD, following SARS-CoV-2 mRNA vaccination or COVID-19. Although it is difficult to determine a causal relationship between SARS-CoV-2 and anti-Jo-1 myositis based on these small numbers, we suspect a SARSCoV- 2 trigger of anti-synthetase syndromes given the typical combination of symptoms and previously demonstrated association with antecedent viral infections. In addition, we have collected nationwide data on myositis specific antibodies (MSAs) in 2019 (pre- COVID-19) and 2021 (during COVID-19) from six medical centers in the Netherlands. We are currently analysing these data to examine whether the proportion of positive MSAs in 2021 is higher as compared to 2019. The results will be presented at the ICNMD.
ABSTRACT
The early stages of the COVID-19 pandemic may have led to a number of behavioral adaptations among Dutch citizens, possibly due to restrictions because of lockdowns, changed orientations toward work, and changes in consumer sentiment. These factors theoretically predict a number of changes in behavior that may have affected people in diverse circumstances in different ways. Among the variables that we study are financial behaviors, health, happiness and emotions. We explore how these variables were affected among households with different sociodemographic conditions, including urbanization, income, gender and age. We use representative panel data from 2019 and 2020 including relevant information from about 2,800 Dutch citizens to study a number of changes primarily during the initial lockdown period in 2020 as compared with the normal situation in 2019. We use regression analysis to estimate the Difference-in-Difference effects of the lockdown in 2020 as compared with the state of affairs in 2019. We find several lockdown effects on transitory thoughts and feelings, i.e., price perceptions, household financial management, emotions, and social relations, of which some effects strongly differ between urban and rural areas. We did not find evidence for more long-lasting effects, for example, on savings, perceived health, and (un)healthy behaviors, although these might have occurred later during the pandemic. Copyright © 2022 Antonides, Goedegebure and van Leeuwen.
ABSTRACT
The collateral damage of a worldwide crisis: The impact of the COVID-19 pandemic on the work experiences of gastroenterologists This study investigated the impact of work changes as a result of COVID-19 on the work experiences of 248 gastroenterologists (GEs) working in Dutch hospitals. Specifically, we studied how the work of GEs changed as a result of the COVID-19 crisis, and what effect this has on burnout, engagement, job satisfaction, employability, work ability, physical and psychological health. Participants completed a questionnaire in the run-up to the second COVID-19 wave in October 2020. Results show that the COVID-19 crisis significantly reduced their number of working hours, and a small proportion of GEs worked temporarily in other units to care for COVID-19 patients. At the time of this study, the impact of these changes on the work experiences of GEs appears to be small. Although before the COVID-19 crisis GEs were slightly more positive about their work ability, physical and mental health than during this crisis, the changes in their work as a result of the COVID-19 crisis had no apparent negative effects on other aspects of their work experience. This study underscores the importance of not equating healthcare workers in drawing conclusions about the impact of the COVID-19 crisis. Different groups can experience the COVID-19 crisis differently, and variation can also exist within professional groups. Attention for work perceptions remains important because doctors who experienced more stress/work pressure reported less favorable outcomes.