Change in body weight of older adults before and during the COVID-19 pandemic: Longitudinal results from the Berlin Aging Study II (preprint)

Background: Change in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. Aims: Describe body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures. Methods: In this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline, average follow-up time 10 years). Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared. Results: On average, women and men lost 0.87% (n=227) and 0.5% (n=245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p<0.05, n=245). Conclusions: Older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.

Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome - results from a prospective observational cohort (preprint)

IntroductionPost-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences. MethodsWe assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria. ResultsWhile PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS. DiscussionDebilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles (preprint)

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

SARS-CoV-2 mRNA vaccination fails to elicit humoral and cellular immune responses in multiple sclerosis patients receiving fingolimod (preprint)

SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. Here we investigated the induction and stability of vaccine-specific antibodies, B cells, and T cells in multiple sclerosis (MS) patients on different DMTs in a prospective cohort study up to 6 months after homologous prime-boost mRNA vaccination. We analysed 103 MS patients of which 86 received anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and compared them to 17 untreated MS patients. In contrast to all other DMTs and untreated patients, treatment with aCD20-BCD or fingolimod significantly reduced anti-S1 IgG, serum neutralizing activity, and RBD- and S2-specific B cells. MS patients receiving fingolimod additionally lacked S1- and S2-reactive CD4 + T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether patients successfully developed humoral immune responses. Fingolimod blocks the ability of immune cells to recirculate and migrate within secondary lymphoid organs demonstrating that functional immune responses require not only immune cells themselves but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses in fingolimod-treated MS patients suggests that these patients are at risk for severe SARS-CoV-2 infections despite vaccination, which is highly relevant for clinical decision-making and adapted protective measures, particularly in light of additional recently approved S1P receptor antagonists for MS treatment.

Serum but not mucosal antibody responses are associated with pre-existing SARS-CoV-2 spike cross-reactive CD4+ T cells following BNT162b2 vaccination in the elderly (preprint)

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed human cellular, serological and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine in old (69-92 years) and middle-aged (24-57 years) vaccinees compared to natural infection (COVID-19 convalescents, 21-55 years). Serological humoral responses to vaccination exceeded those of convalescents but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4 + T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4 + T cells as predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.

Chronic COVID-19 / Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany and biomarkers associated with symptom severity (preprint)

A subset of patients has long-lasting symptoms after mild to moderate COVID-19. In a prospective observational cohort study we analysed clinical and laboratory parameters in 42 patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19 referred to as Chronic COVID-19 Syndrome (CCS). Most patients were moderately to severely impaired in daily live. 19 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome referred to as CFS/CCS. Hand grip strength (HGS) was diminished in most patients. Association of several biomarker with key symptoms of physical and mental fatigue and post exertional malaise indicate low level inflammation and hypoperfusion as potential pathomechanisms.