Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study (preprint)

Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10g BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3g BNT162b2, no sex differences were noted, but after a first dose of 5 or 10g BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).

Real-world Effectiveness and Causal Mediation Study of BNT162b2 on Long COVID Risks in Children and Adolescents (preprint)

BackgroundThe impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. Further, it is unknown if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection. ObjectiveTo assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. To disentangle the overall effectiveness of the vaccine on long COVID outcomes into its independent impact and indirect impact via prevention of SARS-CoV-2 infections, using causal mediation analysis. DesignReal-world vaccine effectiveness study and mediation analysis in three independent cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SettingTwenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Participants112,590 adolescents (88,811 vaccinated) in the Delta period, 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) in the Omicron period. ExposuresFirst dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. MeasurementsOutcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)*100 and mediating effects were reported as relative risks. ResultsDuring the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9% to 97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3% to 73.5%) and 75.1% (95% CI: 50.4% to 87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimates of 1.08 (95% CI: 0.75 to 1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92 to 1.66) among children and 0.91 (95% CI: 0.69 to 1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03 to 0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23 to 0.42) among children and 0.21 (95% CI: 0.16 to 0.27) among adolescents during the Omicron period. LimitationsObservational study design and potentially undocumented infection. ConclusionsOur study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccines effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Primary Funding SourceNational Institutes of Health.

Influence of the COVID-19 Pandemic on the Treatment of immune mediated Rheumatic and Musculoskeletal Diseases during the first pandemic period: A Systematic Review (preprint)

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces (preprint)

Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses and materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate the role of receptor-binding domain (RBD) mutations on the adsorption of SARS-CoV-2 to hydrophobic and hydrophilic surfaces employing molecular simulations. To contextualize our findings, we contrast the interactions on inanimate surfaces with those on native-biological interfaces, specifically the ACE2 receptor. Notably, we identify a twofold increase in structural deformations for the proteins receptor binding motif onto the inanimate surfaces, indicative of enhanced shock-absorbing mechanisms. Furthermore, the distribution of amino acids (landing-footprints) on the inanimate surface reveals a distinct regional asymmetry relative to the biological interface. In spite of the H-bonds formed at the hydrophilic substrate, the simulations consistently show a higher number of contacts and interfacial area with the hydrophobic surface, with the WT RBD adsorbed more strongly to than the delta or omicron RBDs. In contrast, the adsorption of delta and omicron to hydrophilic surfaces was characterized by a distinctive hopping-pattern. The novel shock-absorbing mechanisms identified in the virus adsorption on inanimate surfaces could lead current experimental efforts in the design of virucidal surfaces.

Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice (preprint)

The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x103 to 3x105 PFU/30 L) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x104 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.

Correlation between COVID-19 vaccination and inflammatory musculoskeletal disorders (preprint)

ImportanceEarlier research on COVID-19 vaccines identified a range of adverse reactions related to proinflammatory actions that can lead to an excessive immune response and sustained inflammation. However, no study has been conducted on the association between inflammatory musculoskeletal disorders and COVID-19 vaccines. ObjectiveTo investigate the incidence rates of inflammatory musculoskeletal disorders following COVID-19 vaccination and to compare them with those of unvaccinated individuals. Design, Setting, and ParticipantsThis retrospective nationwide cohort study used data from the Korean National Health Insurance Service (NHIS) database, involving 2,218,715 individuals. Data were collected from January 1, 2021, to 12 weeks after the second dose of vaccine for vaccinated individuals and 12 weeks after September 30, 2021, for unvaccinated individuals. ExposuresStatus was categorized as unvaccinated and vaccinated with mRNA vaccine, viral vector vaccine, and mixing and matching. Main Outcomes and MeasuresThe primary outcome was the occurrence of inflammatory musculoskeletal disorders that were selected as plantar fasciitis (ICD code, M72.2), rotator cuff syndrome (M75.1), adhesive capsulitis (M75.0), herniated intervertebral disc (HIVD) (M50.2/M51.2), spondylosis (M47.9), bursitis (M71.9), Achilles tendinitis (M76.6), and de-Quervain tenosynovitis (M65.4). Multivariate logistic regression analysis was used to determine the risk factors of musculoskeletal disorders after adjusting for potential confounders. ResultsAmong the 2,218,715 individuals, 1,882,640 (84.9%) received two doses of the COVID-19 vaccine, and 336,075 (15.1%) did not. At 12 weeks after vaccination, the incidences of plantar fasciitis (0.14-0.17%), rotator cuff syndrome (0.29-0.42%), adhesive capsulitis (0.29-0.47%), HIVD (0.18-0.23%), spondylosis (0.14-0.23%), bursitis (0.02-0.03%), Achilles tendinitis (0.0-0.05%), and de-Quervain tenosynovitis (0.04-0.05%) were higher in all three vaccinated groups (mRNA, cDNA, and mixing and matching vaccines) when compared to the unvaccinated group. All COVID-19 vaccines were identified as significant risk factors for each inflammatory musculoskeletal disorder (odds ratio, 1.404-3.730), except for mixing and matching vaccines for de-Quervain tenosynovitis. Conclusions and RelevanceThis cohort study found that individuals who received any COVID-19 vaccine were more likely to be diagnosed with inflammatory musculoskeletal disorders than those who did not. This information will be useful in clarifying the adverse reactions to COVID-19 vaccines and informing people about their potential for inflammatory musculoskeletal disorders after vaccination.

Patterns in Domestic Injuries and how COVID-19 Lockdown Measures Changed Their Incidence in Mexico (preprint)

Domestic accidents occur worldwide. From small burns and bruises to significant wounds and injuries from dangerous falls, not all of them reach clinical care; so to measure the toll of these hardships on society, we surveyed three major cities in Mexico to better understand the problem and how coronavirus disease 2019 (COVID-19) lockdown measures changed the incidence rate. We conducted an analytical cross-sectional study using Microsoft Forms, with a digital survey distributed among the Mexican population from October 2021 to November 2021, during lockdown. The incidence of all injuries surveyed increasedduring the first year of the COVID-19 pandemic. A comparison of the time spent inside the house before and during the pandemic showed that only burns increased. The number of wounds and musculoskeletal injuries decreased as people spent more time at home. Women were shown to be the most vulnerable group. This study offers an unprecedented perspective on home-related trauma, as past literature has mainly examined trauma injuries treated in hospitals. The types of wounds have morphed depending on the percentage of time spent in the house, which has undergone a remarkable transformation since the lockdown was enacted.

Editorial to the Special Issue "The Effect of Exercise Intensity and Psychological Intervention on Musculoskeletal Disorders".

Musculoskeletal disorders are responsible for the most prevalent form of pain, and necessitate a comprehensive approach to rehabilitation [...].

Frequency and risk factors of musculoskeletal disorders in high risk occupation workers in Urban, Karachi.

OBJECTIVE: To determine the frequency and risk factors of musculoskeletal disorders in high-risk occupation workers in an urban setting. METHODS: The analytical cross-sectional study was conducted in Karachi from July to December 2020, and comprised office workers, operation theatre technicians and coolies. The presence of musculoskeletal disorders was assessed using the Nordic Musculoskeletal Questionnaire to determine factors associated with moderate to severe condition. Data was analysed using SPSS 20. RESULTS: Of the 300 male subjects, 100(33.3%) each were office workers, operation theatre technicians and coolies. The overall mean age was 33.25±6.8 years (range: 18-50 years). The overall prevalence of musculoskeletal disorders was 179(59.7%). Besides, 117(65.4%) patients with musculoskeletal disorders had intermediate stage of the disease. The lower back and neck were the most common site of trouble involved in preceding 12 months 111(43.6%) each. CONCLUSIONS: Prevalence of musculoskeletal disorders was found to be a common problem affecting high-risk occupational workers.

Facilitators and barriers for vaccination in patients with inflammatory rheumatic musculoskeletal diseases: a prospective cohort study.

INTRODUCTION: To identify facilitators and barriers towards vaccination in general and specifically against pneumococci, influenza and SARS-CoV-2 in patients with rheumatic musculoskeletal diseases (RMD). METHODS: Between February and April 2021, consecutive patients with RMD were asked to complete a structured questionnaire on general knowledge about vaccination, personal attitudes and perceived facilitators and barriers towards vaccination. General facilitators (n=12) and barriers (n=15) and more specific ones for vaccination against pneumococci, influenza and SARS-CoV-2 were assessed. Likert scales had four response options: from 1 (completely disagree) to 4 (completely agree). Patient and disease characteristics, their vaccination records and attitudes towards vaccination against SARS-CoV-2 were assessed. RESULTS: 441 patients responded to the questionnaire. Knowledge about vaccination was decent in ≥70% of patients, but <10% of patients doubted its effectiveness. Statements on facilitators were generally more favourable than on barriers. Facilitators for SARS-CoV-2 vaccination were not different from vaccination in general. Societal and organisational facilitators were more often named than interpersonal or intrapersonal facilitators. Most patients indicated that recommendations of their healthcare professional would encourage them to be vaccinated-without preference for general practitioner or rheumatologists. There were more barriers towards SARS-CoV-2 vaccination than to vaccination in general. Intrapersonal issues were most frequently reported as a barrier. Statistically significant differences in response patterns to nearly all barriers between patients classified as definitely willing, probably willing and unwilling to receive SARS-CoV-2 vaccines were noted. DISCUSSION: Facilitators towards vaccination were more important than barriers. Most barriers against vaccination were intrapersonal issues. Societal facilitators identified support strategies in that direction.

Influence of Vitamin D Supplementation on Bone Mineral Content, Bone Turnover Markers and Fracture Risk in South African Schoolchildren: Multicentre Double-Blind Randomised Placebo-Controlled Trial (ViDiKids) (preprint)

Background: Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking.Methods: We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial.Findings: 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs. placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6, P<0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17, P=0.005). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI -1.3 to 0.8), or for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48).Interpretation: Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk.FUNDING: Medical Research CouncilTrial Registration: Registered on the South African National Clinical Trials Register (DOH-27-0916-5527) and ClinicalTrials.gov (ref NCT02880982).Funding: This research was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1, both awarded to ARM). RJW was supported by Wellcome (104803, 203135). He also received support from the Francis Crick Institute which is funded by Cancer Research UK (FC2112), the UK Medical Research Council (FC2112) and Wellcome (FC2112). Declaration of Interest: ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests.Ethical Approval: The trial was sponsored by Queen Mary University of London, approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2).

Long-Term Safety Analysis of the ChAdOx1-nCoV-19 Corona Virus Vaccine: Results from a Prospective Observational Study in Priority Vaccinated Groups in North India.

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. OBJECTIVE: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. METHODS: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA® SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. CONCLUSION: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events forpaxlovid and molnupiravir (preprint)

Questions have been raised about the safety of paxlovid and molnupiravir as antiviral drugs for the treatment of COVID-19 since the pandemic. We applied t he FDA Adverse Event Reporting System (FAERS) to assess the safety by performing a disproportionality analysis to identify potential risks of paxlovid and molnupiravir. The number of paxlovid signals was approximately 11 times higher than that of molnupiravir, with most signals of these two drugs overlapped. General disorders and administration site conditions (ROR: 0.52, 95% CI: 0.58- 2.18), infections and infestations (ROR: 0.18, 95% CI: 0.23-6.64), nervous system disorders (ROR: 1.41, 95% CI: 0.79-1.58) were the top 3 signals for paxlovid, with gastrointestinal disorders (ROR: 4.13, 95% CI: 0.27-4.54), skin and subcutaneous tissue disorders (ROR: 11.51, 95% CI: 0.10-12.92), nervous system disorders (ROR: 1.41, 95% CI: 0.79-1.58) for molnupiravir. Paxlovid-induced infections, skin and subcutaneous tissue disorders, and molnupiravir-induced musculoskeletal and connective tissue disorders, as well as potential safety signals on the heart, eyes and ears needlong-term observation, especially for signals not included in the instructions. The adverse events on this study confirms most of the instructional information for paxlovid and molnupiravir, both drugs need to be monitored for risk signals such as acute respiratory failure, hematologic and lymphatic system.

Postacute Sequelae of SARS-CoV-2: Musculoskeletal Conditions and Pain.

Musculoskeletal and pain sequelae of COVID-19 are common in both the acute infection and patients experiencing longer term symptoms associated with recovery, known as postacute sequelae of COVID-19 (PASC). Patients with PASC may experience multiple manifestations of pain and other concurrent symptoms that complicate their experience of pain. In this review, the authors explore what is currently known about PASC-related pain and its pathophysiology as well as strategies for diagnosis and management.

Examination of Musculoskeletal System Disorders and Ergonomic Conditions in the Work Environment of Academics Providing Distance Education During the COVID-19 Pandemic: Controlled Study.

BACKGROUND This study aimed to evaluate whether the incidence rate of musculoskeletal system disorders changed owing to the increase in the time spent on the computer by academics who did or did not provide distance education during the COVID-19 pandemic. MATERIAL AND METHODS The Cornell Musculoskeletal Discomfort Questionnaire was used to assess musculoskeletal discomfort experienced in the past 1 week. In addition, the Occupational Safety and Health Administration (OSHA) Computer Workstations Evaluation Checklist was used to assess the ergonomic structure of the work environment. The questionnaire assessed musculoskeletal system disorders and collected demographic characteristics. RESULTS The study group included 184 (101 male, 83 female) academics who provided distance education, whereas the control group included 82 (44 male, 38 female) academics who did not provide distance education. The mean ages of academics in the study group and control group were 37.46±7.34 and 41.26±10.06 years, respectively. Although computer-based work environment ergonomics were similar (P>0.05) in both groups during the pandemic, the incidence rate of musculoskeletal disorders was significantly high in the study group (P<0.001). These disorders were mostly seen in the neck, back, and waist regions (P<0.001). CONCLUSIONS The results suggested that the incidence rate of musculoskeletal disorders increased in academics who provided distance education during the COVID-19 pandemic.

Investigation of musculoskeletal disorders, physical activity level, sleep quality, and fatigue in health professionals with and without a history of COVID-19.

BACKGROUND: Healthcare workers belong to an occupational group that is at high risk during the coronavirus 2019 (COVID-19) pandemic. The increased workload of healthcare workers and the accompanying psychosocial stress caused by the pandemic can affect musculoskeletal system disorders, physical activity status, sleep quality, and fatigue in this group. OBJECTIVE: To investigate musculoskeletal system disorders, physical activity level, sleep quality, and fatigue in healthcare workers with and without a COVID-19. METHODS: A total of 200 healthcare professionals aged 18-65 years with and without a history of COVID-19 were in the study. Data were collected between January and March 2021. A "Preliminary Evaluation Form", "Extended version of the Nordic Musculoskeletal System Questionnaire (NMQ-E)", "the International Physical Activity Questionnaire-Short Form (IPAQ-SF)" and "the Pittsburgh Sleep Quality Index (PSQI) were used for data collection". RESULTS: It was determined that musculoskeletal system disorders did not differ significantly between healthcare workers with and without a COVID-19 history (p > 0.05). It was found that the number of people with problems in the low-back region was higher in those with a COVID-19 history (p = 0.002). In the sleep duration component, the scores of those who did not have a COVID-19 history were found to be significantly higher than those who did (p = 0.10). In other comparisons, it was determined that there was no significant difference. CONCLUSIONS: It was found that the number of people with problems in the low-back region was higher in those with a COVID-19 history. Those without a COVID-19 history had higher scores in sleep duration parameter.

Digital health in musculoskeletal care: where are we heading?

BMC Musculoskeletal Disorders launched a Collection on digital health to get a sense of where the wind is blowing, and what impact these technologies are and will have on musculoskeletal medicine. This editorial summarizes findings and focuses on some key topics, which are valuable as digital health establishes itself in patient care. Elements discussed are digital tools for the diagnosis, prognosis and evaluation of rheumatic and musculoskeletal diseases, coupled together with advances in methodologies to analyse health records and imaging. Moreover, the acceptability and validity of these digital advances is discussed. In sum, this editorial and the papers presented in this article collection on Digital health in musculoskeletal care will give the interested reader both a glance towards which future we are heading, and which new challenges these advances bring.

Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier.

Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.

Teleworking and Musculoskeletal Disorders: A Systematic Review.

Teleworking has spread drastically during the COVID-19 pandemic, but its effect on musculo-skeletal disorders (MSD) remains unclear. We aimed to make a qualitative systematic review on the effect of teleworking on MSD. Following the PRISMA guidelines, several databases were searched using strings based on MSD and teleworking keywords. A two-step selection process was used to select relevant studies and a risk of bias assessment was made. Relevant variables were extracted from the articles included, with a focus on study design, population, definition of MSD, confounding factors, and main results. Of 205 studies identified, 25 were included in the final selection. Most studies used validated questionnaires to assess MSD, six considered confounders extensively, and seven had a control group. The most reported MSD were lower back and neck pain. Some studies found increased prevalence or pain intensity, while others did not. Risk of bias was high, with only 5 studies with low/probably low risk of bias. Conflicting results on the effect of teleworking on MSD were found, though an increase in MSD related to organizational and ergonomic factors seems to emerge. Future studies should focus on longitudinal approaches and consider ergonomic and work organization factors as well as socio-economic status.