Evaluation of diseases complicating long COVID: A retrospective chart review (preprint)

Purpose Evidence for the pathogenesis and treatment of post-acute coronavirus disease 2019 (COVID-19) (long COVID) is lacking. As long COVID symptoms are predicted to have an impact on the global economy, clarification of the pathogenesis is urgently needed. Our experiences indicated that some symptoms were complicated by diseases established before the COVID-19 pandemic.Methods Using a retrospective, cross-sectional study, we aimed to evaluate the diseases complicating long COVID. Using the medical records of patients with confirmed severe acute respiratory syndrome coronavirus 2 infection exhibiting residual symptoms lasting ≥ 60 days post-infection who visited our clinic in January 2021–February 2023, we investigated the symptoms and diseases observed. We identified diseases that occurred after COVID-19 infection and excluded those that were exacerbations of existing diseases. Results: During the first visit, the most common symptoms reported in a total of 798 patients were fatigue (523 patients), anxiety (349 patients), and lack of motivation (344 patients). Complicating diseases were observed in 452 patients (57%). There were 115, 65, and 60 patients with postural tachycardia syndrome, postural syndrome without tachycardia, and mood disorders, respectively. Some diseases requiring immediate treatment included pulmonary thromboembolism, purulent shoulder arthritis, cerebellopontine angle tumors, myasthenia gravis, and cervical myelopathy.Conclusion All symptoms that occur after COVID-19 infection should not be treated as long COVID. Similar to normal medical treatment, a list of differential diagnoses should be maintained based on symptoms to obtain definitive diagnoses.

Social determinants of recovery from ongoing symptoms following COVID-19 in two UK longitudinal studies: a prospective cohort study (preprint)

BackgroundSocial gradients in COVID-19 exposure, illness severity, and mortality have been observed in multiple international contexts. Whether pre-existing social factors affect recovery from ongoing symptoms following COVID-19 and long COVID is less well understood. MethodsWe analysed data on self-perceived recovery following self-reported COVID-19 illness in two United Kingdom community-based cohorts, COVID Symptom Study Biobank (CSSB) (N = 2548) and TwinsUK (N = 1334). Composite variables quantifying socio-demographic advantage and disadvantage prior to the COVID-19 pandemic were generated from sex, ethnic group, education, local area deprivation and employment status. Associations between self-perceived recovery and composite variables were tested with multivariable logistic regression models weighted for inverse probability of study participation, adjusting for potential confounding by age, region and pre- pandemic health factors, and potential mediation by COVID-19 illness characteristics and adverse experiences during the pandemic. Further analyses tested associations between recovery and individual socio-demographic variables reflecting status prior to and during the COVID-19 pandemic. FindingsSocio-demographic gradients in recovery were observed, with unadjusted recovery rate varying between 50% and 80% in CSSB and 70% and 90% in TwinsUK based on composite socio-demographic variables. Likelihood of recovery was lower for individuals with more indicators of pre-pandemic social disadvantage in both cohorts (CSSB: odds ratio, OR = 0.74, 95% confidence interval, CI: 0.62-0.88, TwinsUK: OR = 0.79, 95% CI: 0.64-0.98 per disadvantage) and higher with more social advantages (CSSB: OR = 1.26, 95% CI: 1.08-1.47, TwinsUK: OR = 1.36, 95% CI: 1.09-1.70 per advantage). Associations were neither explained by differences in COVID-19 illness severity or timing, nor adverse social experiences during the pandemic, which were themselves inversely associated with recovery. InterpretationStrong social inequalities in the likelihood of recovery from COVID-19 were observed, with ongoing symptoms several months after coronavirus infection more likely for individuals with multiple indicators of social disadvantage. Work is needed to identify modifiable biopsychosocial factors to enable interventions that address inequalities. FundingChronic Disease Research Foundation, National Institute for Health and Care Research, Medical Research Council, Wellcome LEAP, Wellcome Trust, Engineering & Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Versus Arthritis, European Commission, Zoe Ltd. Plain language summaryAcross the world acute COVID-19 illness has affected the most disadvantaged in society the most. However, we have not looked in detail whether peoples social circumstances affect their recovery from COVID-19. In our study, we asked people from two UK-based health studies if they still had symptoms after having COVID-19. We looked at how advantaged or disadvantaged they were at the start of the pandemic, based on information about their sex, ethnic group, education level, local area, and employment. In both studies, people who were more disadvantaged were more likely to still have symptoms long after having COVID-19. In contrast, more advantaged people were more likely to have fully recovered. We also saw that people who had negative experiences during the pandemic such as losing their job, being unable to afford their bills or not being able to access health & social care services were less likely to recover. More work is needed to understand how and why recovery was so different for people with different circumstances. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo search for previous reports on associations between recovery from COVID-19 and socio-demographic factors, we screened abstracts identified from the PubMed search query on December 21, 2023: "((COVID-19) AND ((recovery) OR (convalescence) OR (" ongoing symptoms")) AND ((socioeconomic) OR (sociodemographic) OR (social) OR (gradient))) AND LitCLONGCOVID[filter]", where LitCLONGCOVID is a filter for articles relating to long COVID (https://pubmed.ncbi.nlm.nih.gov/help/#covid19-article-filters), which returned 210 results published between July, 2020 and December, 2023. A small number (N = 11) of studies contained direct measures of recovery from COVID-19 in terms of presence/absence of ongoing symptoms relating to COVID-19 illness, either as perceived by the individual or inferred from current symptom reports. Of these, most focused on associations with COVID-19 illness factors such as severity and symptomatology, and prior health indicators. Socio-demographics were mostly used for sample description and adjustments in models rather than as exposures of interest. Of the few studies (N = 8) that tested associations with socio-demographic variables, the range of socio-demographics tested was limited and/or follow-up time typically restricted to 6-12 months since symptom onset. In these studies, associations with recovery were reported for age (N = 4), sex (N = 7), race/ethnicity (N = 2), local area deprivation (N = 1), and education level (N = 1). Associations between long-term symptoms and education or income have been reported in single separate studies. Monthly bulletins up to March 2023 from the UK Coronavirus Infection Survey highlighted prevalence of individuals reporting current effects on daily activities due to long COVID was associated with age, sex, race/ethnicity, local area deprivation and economic activity. No studies were identified that tested for associations of multiple socio-demographics in combination with the likelihood of recovery following COVID-19. Added value of this studyThis is the first study to testing the effects of multiple socio-demographics on self-perceived recovery in combination. Measures that attempt to quantify social advantage and disadvantage were generated from multiple known social determinants of health. We tested a wider range of socio-demographic factors than previous studies, including UK geographic region, educational qualification level, employment status and income. Our study has a longer follow-up time than previous comparable reports, with most participants assessed more than one year after infection onset. Detailed data on health before the coronavirus pandemic and COVID-19 illness allowed models to be adjusted extensively and mediation effects to be tested. Implications of all the available evidenceThe likelihood of full recovery following COVID-19 appears to follow a social gradient, higher for individuals with multiple indicators of social advantages and fewer disadvantages, and lower for those with multiple social disadvantages and fewer advantages prior to the coronavirus pandemic. This reflects and reaffirms the established cycle of social inequalities in health, between individuals status within social hierarchies and ill-health. More work is needed to understand the pathways through which this inequality operates so that interventions can be made.

The impact of the COVID-19 pandemic on patients with juvenile idiopathic inflammatory myopathies (preprint)

Background: Throughout the COVID-19 pandemic, there have been concerns regarding the risks of infection in patients with autoimmune disease. In this study, we investigated the impact of the pandemic on patients with juvenile idiopathic inflammatory myopathies (JIIM). Methods: Data were collected using a patient/caregiver survey via Research Electronic Data Capture (REDCap) database. Eligibility included JIIM diagnosis and current age less than 21 years old. Surveys were distributed via the CureJM organization, social media, Childhood Arthritis and Rheumatology Research Alliance (CARRA) network and Dr. Peter Dent Pediatric Rheumatology Bulletin Board. Results: Eighty-four respondents accessed the survey, 70 (83%) consented to participate, and 54 out of 70 completed the full survey (77%). Twenty-seven out of 57 patients (47%) tested positive for COVID-19, with 7 (12%) testing positive more than once. Despite broad usage of immunosuppressive medications, 24 out of 27 (89%) reported mild symptoms with none requiring hospitalization. Four patients reported a flare of JIIM symptoms after COVID-19; three of whom held immunomodulatory medications during their infection. Thirty-seven out of 54 respondents (69%) reported vaccination against COVID-19, with 9 out of 37 (24%) reporting minor vaccine side effects and one reporting JIIM flare post vaccination. Twenty-one out of 54 (39%) respondents reported psychosocial concerns related to the COVID-19 pandemic. Conclusions: Patients with JIIM, including those on multiple immunosuppressive medications, had mild symptoms related to COVID-19. Most patients tolerated COVID-19 vaccination well. Few patients had disease flare post-COVID-19 or vaccination. Mental health concerns were demonstrated in JIIM patients during the COVID-19 pandemic.

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients.

Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study (preprint)

Introduction Older adults are usually more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher probability of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. Methods This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA), who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns of chronic conditions were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19 related outcomes were examined using multivariable logistic regression. Results Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR=1.87, 95% CI=1.42-2.46) but not of COVID-19 related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR=1.56, 95% CI=1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR=1.46, 95% CI=1.23-1.74), lung diseases (OR=1.40, 95% CI=1.17-1.69), psychiatric conditions (OR=1.40, 95% CI=1.16-1.68), retinopathy/eye diseases (OR=1.39, 95% CI=1.18-1.64), and arthritis (OR=1.27, 95% CI=1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. Discussion/Conclusion This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and highlights the importance of CVD and complex comorbidities. These findings facilitate crucial new evidence for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

HLA-B27 did not protect against COVID-19 in patients with axial Spondyloarthritis – Data from the ReumaCov-Brasil Registry (preprint)

Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), with (cases) and without (control group) COVID-19 diagnosis, were paired to sex and age. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanic ventilation and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 269 axial SpA patients were included, of whom 165 (61.3%) with COVID-19 and 104 (38.7%) without COVID-19. Most of them were men (N = 153; 56.9%) with mean age of 46.3 ± 13.8 years and long-term disease (13.1 ± 9.9 years). There were no significant statistically differences concerning social distancing, smoking, BMI, waist circumference and comorbidities. Regarding b-DMARDs, 134 (75.3%) were on TNF inhibitors and 17 (9.6%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 45, 73.8% vs. n = 38, 73.1%, respectively; p = 0.93). In addition, disease activity was similar before and after the infection. On the other hand, the control group had significantly higher disease activity score, according to ASDAS-CRP (2.8 ± 1.8 vs. 1.8 ± 1.2, p = 0.03). Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.2 ± 3.6 days, with length of hospitalization quite similar between patients who died and those discharged (12.6 ± 7 and 13.9 ± 11.7, respectively). The global death estimation for COVID-19 was 1.9 (95%CI 0.6–4.3), regardless HLA-B27 status. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Aggravation of Psoriasis Following Covid-19: A Study of 105 Patients (preprint)

Background: SARS-Cov 2 2019 (C-19) infection affects the course of various dermatological diseases. However, data on its impact on psoriasis course is limited. Objectives: To evaluate the impact of C-19 infection on psoriasis course and also investigate the frequency of post-covid complications in psoriasis patients. Methods: Psoriasis patients with at least one C-19 PCR positivity, having a control visit between March and June 2022 were included. The flare was defined as at least 25% increase in psoriasis severity within 4 weeks after C-19 PCR positivity, according to patient-reported assessment. As confounders, corticosteroid and hydroxychloroquine use and vaccination against SARS-Cov2 histories within the last 4 weeks were questioned. Also, post-covid complications were recorded. Results: 105 patients (50 female, 55 male) with a total of 113 C-19 incidents were included. Psoriasis exacerbation following C-19 was observed in 23.8% (n:25) of patients. Among 22 patients, exacerbation was similar to baseline psoriasis phenotype (1 guttate, 2 generalized pustular, 19 plaque) whereas in 3 patients with plaque psoriasis, guttate (2) and generalized pustular (1) psoriasis emerged. The risk of post-covid psoriasis flare was found to be related with discontinuation of medications or unstable psoriasis during C-19. Six patients developed post-covid complications including pericardial effusion, pulmonary thromboembolism, cerebrovascular accident, fascial paralysis and arthritis. Conclusion: This study shows a high risk of psoriasis flare following C-19, which is mostly related to unstable psoriasis during C-19 or discontinuation of medications. Since psoriasis patients have increased risk of cardiovascular complications, careful follow-up for mainly thrombotic post-covid complications is mandatory. IRB approval status: Reviewed and approved by Marmara University School of Medicine IRB (Approval number: 09.2022.339)

A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and "long" COVID19 syndromes. (preprint)

Objectives Characterization of tissue laxity and dysautonomia symptoms in Ehlers-Danlos syndrome (EDS) uncovered similarities with those of post-infectious SARS-CoV-2 or long COVID19, prompting detailed comparison of their findings and influencing genes. Methods Holistic assessment of 1261 EDS outpatients for 120 history-physical findings populated a deidentified database that includes 568 patients with 317 variant genes obtained by commercial NextGen sequencing. Findings were compared to 15 of long COVID19 compiled in an extensive review, genes to 104 associated with COVID19 severity in multiple molecular studies. Results Fifteen symptoms common to Ehlers-Danlos versus long COVID19 ranged from brain fog (27-80 versus 30-70%), chronic fatigue (38-91; 30-60%), dyspnea (32-52; 29-52%) to irritable bowel (67-89; 14-78%), muscle weakness (22-49; 15-25%), and arthritis (32-94; 15-27%). Genes relevant to EDS included 6 identical to those influencing COVID19 severity (F2, LIFR, NLRP3, STAT1, T1CAM1, TNFRSF13B) and 18 similar including POLG-POLD4, SLC6A2-SLC6A20, and NFKB1-NFKB2. Both gene sets had broad genomic distribution, many mitochondrial genes influencing EDS and many involved with immunity-inflammation modifying COVID19 severity. Recurring DNA variants in EDS that merit evaluation in COVID19 resistance include those impacting connective tissue elements--51 in COL5 (joint), 29 in COL1/2/9/11 (bone), 13 in COL3 (vessel), and 18 in FBN1 (vessel-heart)--or neural function--93 in mitochondrial DNA, 28 in COL6/12, 16 in SCN9A/10A/11A, 14 in POLG, and 11 in genes associated with porphyria. Conclusions Holistic ascertainment of finding pattern and exome variation in EDS defined tissue laxity, neuromuscular, and autonomic correlations that transcend single abnormalities or types. Implied networks of nuclear and mitochondrial genes are linked to findings like brain fog, fatigue, and frailty in EDS, their similarity to long COVID19 supporting shared therapies for disorders affecting a minimum 0.1% of the global population.

[Massive pancarditis-autopsy report]. / Massive Pankarditis ­ ein Autopsiebericht.

We report on a 69-year-old man suffering from chronic progressive oligoarthritis (localized in metacarpal and knee joints), which clinically was interpreted as steroid-sensitive seronegative chronic arthritis. The patient died from sudden death at the emergency department after a 4-week history of increasing cough and dyspnea (meanwhile obtaining negative testing results for SARS-CoV-2). During the autopsy, we found massive pancarditis affecting all cardiac compartments, in particular exhibiting constrictive pericarditis, myocarditis, and multivalvular endocarditis. Microscopically, interstitial myocarditis could be observed. Performing extensive molecular analyses, we detected Tropheryma whipplei in the tissue specimens of the heart, but not in various duodenal tissue probes or in the synovial membrane. Taken together, in the present case the cause of death was acute cardiac failure due to multivalvular pancarditis due to T. whipplei. Besides from classical symptoms and morphological signs, Whipple's disease may present with various features. Regarding the differential diagnosis of a chronic multisystem disorder with aspects of hitherto unknown arthralgia, Whipple's disease should be considered.

Job retention vocational rehabilitation for employed people with inflammatory arthritis: adaptations to the WORKWELL trial due to the impact of the COVID-19 pandemic.

There are high levels of work disability, absenteeism (sick leave) and presenteeism (reduced productivity) amongst people with inflammatory arthritis. WORKWELL is a multi-centre, randomised controlled trial of job retention vocational rehabilitation for employed people with inflammatory arthritis. The trial tested the effectiveness and cost-effectiveness of the WORKWELL programme compared to the receipt of written self-help information only. Both arms continued to receive usual care. In March 2020, due to the COVID-19 pandemic, the WORKWELL trial paused to recruitment and intervention delivery. To successfully re-start, protocol amendments were rapidly submitted and changes to existing trial procedures were made. The WORKWELL protocol was adapted in response to both the practical issues likely faced by many clinical research studies active across NHS sites during the pandemic and additional trial-specific challenges. A key eligibility criterion for the trial required participants to be in paid work for at least 15 h per week. However, UK national lockdowns led to a substantial proportion of the workforce suddenly being furloughed or unable to work, and many people with arthritis taking immunosuppressive medications were asked to shield themselves. Thus, the number of eligible participants was reduced. Those continuing to work were harder to identify, as hospital clinics moved to remote delivery, and also to then screen, consent and treat, as the hospital research staff and clinical therapists were re-deployed. New recruitment and consent strategies were applied, and where sites had reduced capacity, responsibilities were absorbed by the trial management team. Remote intervention delivery and electronic data capture were also implemented. By rapidly adapting the WORKWELL protocol and procedures, the trial successfully reopened to recruitment in July 2020, only 4 months after the trial pause. We were able to achieve recruitment figures above the pre-COVID target and maintain a high retention rate. In addition, we found many of the protocol changes beneficial, as these streamlined trial procedures, thus improving efficiency. It is likely that many strategies implemented in response to the pandemic may become standard practice in future research within trials of a similar design and methodology.Trial registration: ClinicalTrials.gov NCT03942783 . Retrospectively registered on 08 May 2019. ISRCTN Registry ISRCTN61762297 . Retrospectively registered on 13 May 2019.

The kinetics of humoral and cellular responses after the booster dose of COVID-19 vaccine in inflammatory arthritis patients (preprint)

Introduction: Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to not unstudied kinetics of the immune response after booster vaccinations. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. Patients and Methods: In 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-{gamma} production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. Results: IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2). Conclusion: Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

Sleep Problems and New Occurrence of Chronic Conditions during the COVID-19 Pandemic in the UK.

The COVID-19 pandemic has negatively impacted upon sleep health. Relatively little is known about how this may influence the population's health subsequently. This prospective longitudinal study aims to examine the consequences of sleep problems for physical and mental health during the COVID-19 pandemic in the UK, using data from the Understanding Society: COVID-19 Study, a large-scale population-based survey with 12,804 adults aged 16 and above. A measure of sleep problems was derived from Pittsburgh Sleep Quality Index (PSQI) questions, reflecting seven dimensions of sleep quality. Binary logistic regressions were applied to investigate the relationship between sleep problem and the incidence of cardiovascular disease (CVD), hypertension, diabetes, obesity, arthritis and an emotional, nervous or psychiatric problem over the 15 months follow-up period. The analysis confirms that sleep problems are prevalent and vary between sub-groups among adults. Notably, sleep problems are then significantly associated with a higher risk of cardiovascular disease, hypertension, diabetes, obesity, arthritis and emotional, nervous or psychiatric problems, independent of demographic, socioeconomic, familial and health confounders. Our findings suggest promoting good sleep hygiene should be prioritised during the pandemic, and more generally as part of wider programmes aimed at promoting good physical and mental health.

Humoral and cellular immunogenicity of COVID-19 booster dose vaccination in inflammatory arthritis patients.

Introduction: Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA). Patients and methods: 49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine. Results: After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine. Conclusion: Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.

Musculoskeletal Manifestations, Post-COVID Syndrome, Relationship with Laboratory Parameters in Hospitalized Patients Infected with COVID-19 (preprint)

Background: This study aims to characterize the prevalence of musculoskeletal manifestations in hospitalized COVID-19 patients and the relationship between C-Reactive protein (CRP) and interleukin levels.Methods: A medical records review study was performed on patients at Baskent University between March 7 and December 31, 2020. The study included hospitalized patients above 18 years diagnosed with COVID-19 by polymerase chain reaction. Pregnant individuals, those with end-stage disease or missing documentation were excluded. Patient demographics and laboratory results were obtained from electronic health records and previous study performed in the same hospital. The relationship between musculoskeletal manifestations, CRP, and interleukin levels were determined. A Pvalue of less than .05 was consideredstatistically significant.Results: Totally, 109 patients were analyzed; 34.86% (n = 38) of the patients had arthralgia, 1.83% (n = 2) had arthritis, 41.28% (n = 45) underwentfatigue, and 32.11% (n = 35) experiencedpost-COVID syndrome. There was no correlation between musculoskeletal manifestations, CRP, and interleukin levels (P > .05). There was positive correlation between post-COVID syndrome, fatigue, duration of O2 support, duration of hospitalization (P < .05), and the patients were elderly. CRP levels were positively correlated with duration of hospitalization, duration of O2 support, history of intensive care, and duration of intensive care (P < .05). Interleukin 6 levels were positively correlated with CRP levels, duration of hospitalization, and O2 support duration (P < .05), but there was no correlation with interleukin 10 levels (P > .05).Conclusion: There was no correlation between musculoskeletal manifestations, CRP, and interleukin levels. Patients who are hospitalized, elderly, abnormally fatigued, or O2 supported should be followed for post-COVID syndrome.

Prevalence of chronic diseases among older adults in EAG and non-EAG states of India and its contextual determinants (preprint)

Background: Although the rising burden of chronic diseases became a major challenge of public policy in India, especially in the ongoing COVID-19 pandemic crisis, there is a lack of awareness and access to healthcare resources and infrastructure in India. Therefore, the present study aims to assess the prevalence of chronic diseases among older adults in Empowered Action Group (EAG) and non-EAG states and their contextual factors. Methods: The study used the Longitudinal Ageing Study in India (LASI), Wave-1 data, the survey was conducted during 2017-18. Bi-variate, spatial analyses, and logistic regression models have been carried out to assess the prevalence of chronic diseases among older adults. Results: The prevalence of at least one chronic disease among older adults in India was about 55% and it was about 50% and 59% in EAG and non-EAG states respectively. The prevalence of hypertension (26%) was the leading chronic disease among older adults in India, followed by gastrointestinal problems (18%), arthritis (16%), diabetes (12%), and chronic lung diseases (6%). The odds of chronic diseases among urban older adults were 39%  (Odds Ratio [OR]=1.39; 95% CI:1.29-1.50) and 30% (OR=1.30; 95% CI:1.24-1.35) higher than their rural counterparts in both EAG and non-EAG states respectively. Conclusion: The study concludes that major contextual factors of chronic diseases were higher age, smoking and using smokeless tobacco, physical inactivity, never working, lack of education, Muslim religion, poor economic status, and residing in urban areas in both EAG and non-EAG states in India.

COVID-19 in a patient with new adult-onset Still disease: A case report.

RATIONALE: Adult-onset Still disease (AOSD) is a systemic autoinflammatory illness of unknown cause. Its manifestations comprise fever; arthritis or arthralgia; and skin rash with high inflammatory markers and ferritin levels. Coronavirus disease 2019 (COVID-19) shares several clinical features and laboratory markers of AOSD: making it challenging to differentiate between the 2 conditions. PATIENT CONCERNS: A 29-year-old woman presented with fever, skin rash, and polyarthritis 4 weeks before admission. Two weeks after illness onset, she had an infection with symptoms similar to those of COVID-19. She observed that her symptoms worsened, and new symptoms appeared including headache; vomiting; diarrhea; and loss of taste and smell. The patient tested positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction. DIAGNOSIS: The patient was diagnosed with AOSD complicated with COVID-19 after exclusion of other possible causes of her illness, such as infections, malignancy, or underlying rheumatological disease. INTERVENTIONS: The patient was administered corticosteroids and methotrexate. The patient responded quickly, particularly to corticosteroids. OUTCOMES: This is the second reported case of COVID-19 in a patient with AOSD. She experienced COVID-19 shortly after having AOSD, indicating that those with AOSD might have a higher risk of COVID-19 infection. Furthermore, she developed the most prevalent COVID-19 symptoms. However, distinguishing most of these symptoms from AOSD manifestations was difficult. LESSONS: Early diagnosis and differentiation between AOSD and COVID-19 and prompt initiation of treatment are required.

Impact of vaccination on post-acute sequelae of SARS CoV-2 infection in patients with rheumatic diseases (preprint)

Objective: Vaccination decreases the risk of severe COVID-19 but its impact on post-acute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC. Methods: We prospectively enrolled SARD patients from a large healthcare system who survived acute infection to complete surveys. The symptom-free duration and the odds of PASC (any symptom lasting [≥] 28 or 90 days) were evaluated using restricted mean survival time and multivariable logistic regression, respectively, among those with and without breakthrough infection ([≥] 14 days after initial vaccine series). Results: Among 280 patients, the mean age was 53 years, 80% were female, and 82% were white. The most common SARDs were inflammatory arthritis (59%) and connective tissue disease (24%). Those with breakthrough infection had more upper respiratory symptoms, and those with non-breakthrough infection had more anosmia, dysgeusia, and joint pain. Compared to those with non-breakthrough COVID-19 infection (n=164), those with breakthrough infection (n=116) had significantly more symptom-free days over the follow-up period (+28.9 days, 95% CI: 8.83, 48.89; p=0.005) and lower odds of PASC at 28 and 90 days (aOR 0.49, 95% CI: 0.29, 0.83 and aOR 0.10, 95% CI: 0.04, 0.22, respectively). Conclusion: Vaccinated patients with SARDs were less likely to experience PASC compared to those not fully vaccinated. These findings support the benefits of vaccination for patients with SARDs and suggest that the immune response to acute infection is important in the pathogenesis of PASC in SARD patients.

Hesitancy for SARS-CoV-2 vaccines and post-vaccination flares in patients with systemic lupus erythematosus.

OBJECTIVES: To study the rate of SARS-CoV-2 vaccination and post-vaccination disease flares in patients with systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled ≥ 4 of the ACR criteria for SLE were identified and their SARS-CoV-2 vaccination status was traced. Flares of SLE at 6-week post-vaccination were reviewed retrospectively. Clinical characteristics of patients with and without vaccination, and those who did or did not experience post-vaccination flares were compared by statistical analyses. RESULTS: 914 adult patients with SLE were studied (92.5 % women, age 48.6 ± 14.0 years; SLE duration 14.5 ± 8.6 years). Two doses of the SARS-Cov-2 vaccines (61.5 % BioNTech; 38.5 % CoronaVac) were received by 449 (49.1 %) patients. The vaccination rate in SLE was significantly lower than that of the adult general population (77.8 %; p < 0.001) at the time of data analysis. Patients who were hesitant for vaccination were more likely to be hypertensive, have a history of neuromuscular manifestations, and a significantly higher organ damage score (1.10 ± 1.45 vs 0.74 ± 1.15; p < 0.001). However, none of these factors were significantly associated with vaccine hesitancy on multivariate analysis. Among 449 vaccinated patients, 37(8.2 %) experienced SLE flares: mild/moderate in 34; severe in 3. In an equal number of unvaccinated SLE controls randomly matched for the post-vaccination observation period, 28(6.2 %) had SLE flares: mild/moderate in 17; severe in 11 (odds ratio [OR] for flare in vaccinated patients 1.40[0.81-2.43]; p = 0.23, adjusted for age, sex, active serology, SLE duration and prednisolone use). In vaccinated patients, logistic regression revealed that active lupus serology before vaccination (OR 2.63[1.05-6.62]; p = 0.04) and a history of arthritis (OR 2.71[1.05-7.00]; p = 0.04) or discoid skin lesion (OR 4.73[1.90-11.8]; p = 0.001) were associated with SLE flares following vaccination, adjusted for confounders. CONCLUSION: Hesitancy for COVID-19 vaccination is common in SLE patients. Vaccination against SARS-CoV-2 is not significantly associated with increased SLE flares. Patients with active SLE serology or a history of arthritis/discoid lesion are more likely to flare after vaccination.

Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources (preprint)

Setting Primary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, Spain Participants Individuals with complete data for the year preceding enrollment or those born at the start of observation time. The cohort comprised 25,720,158 subjects. Interventions First and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine. Main outcome measures 29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells’ palsy, chilblain-like lesions death, erythema multiforme, Guillain Barré Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE) Results 12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare <10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia. Conclusion We showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.