Post-Acute COVID-19 Joint Pain and New Onset of Rheumatic Musculoskeletal Diseases: A Systematic Review.

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases.

An Unusual Case of “Conjugal”Polymyalgia Rheumatica after SARS-CoV-2 Vaccination

The rare occurrence of polymyalgia rheumatica (PMR) in married couples has been reported in the literature. Susceptibility to PMR is contributed by genetic and environmental factors and cases of PMR developing after influenza vaccine have also been described, in a debated phenomenon known as 'ASIA’syndrome. We report the case of two cohabitating married patients developing PMR few weeks after the first dose of ChAdOx1-S SARS-CoV-2 vaccine. Both patients presented with typical symptoms suggestive of PMR. Laboratory findings and ultrasound examination confirmed the diagnosis. Glucocorticoid therapy led to rapid improvment of symptoms. Anti-receptor-binding domain IgG titre was tested and, eight weeks after vaccination, both patients showed no antibody response. It has been suggested that vaccines might trigger autoimmune or inflammatory states in predisposed individuals and various hypotheses have been made regarding the pathogenesis of PMR. Although the causative effect of vaccines cannot be determined, the close temporal correlation observed in our case supports the potential role of environmental factors in triggering the onset of PMR. However, the literature indicates that post-COVID19 vaccination immune-mediated or inflammatory adverse events are extremely rare and vaccination should be encouraged since the benefit largely outweighs possible risks.

Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.

OBJECTIVE: Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19. METHODS: Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey. RESULTS: A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents. CONCLUSION: Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.

Higher 90-Day Mortality after Surgery for Hip Fractures in Patients with COVID-19: A Case-Control Study from a Single Center in Italy.

The mortality of hip fracture (HF) patients is increased by concomitant COVID-19; however, evidence is limited to only short follow-up. A retrospective matched case-control study was designed with the aim to report the 90-day mortality and determine the hazard ratio (HR) of concomitant HF and COVID-19 infection. Cases were patients hospitalized for HF and diagnosed with COVID-19. Controls were patients hospitalized for HF not meeting the criteria for COVID-19 diagnosis and were individually matched with each case through a case-control (1:3) matching algorithm. A total of 89 HF patients were treated during the study period, and 14 of them were diagnosed as COVID-19 positive (overall 15.7%). Patients' demographic, clinical, and surgical characteristics were similar between case and control groups. At 90 days after surgery, 5 deaths were registered among the 14 COVID-19 cases (35.7%) and 4 among the 42 HF controls (9.5%). COVID-19-positive cases had a higher risk of mortality at 30 days (HR = 4.51; p = 0.0490) and 90 days (HR = 4.50; p = 0.025) with respect to controls. Patients with concomitant HF and COVID-19 exhibit high perioperative mortality, which reaches a plateau of nearly 30-35% after 30 to 45 days and is stable up to 90 days. The mortality risk is more than four-fold higher in patients with COVID-19.

Mortality in tocilizumab-treated patients with COVID-19: a systematic review and meta-analysis.

OBJECTIVES: People who are exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop a potentially fatal disease with lung involvement and severe cytokine storm syndrome (CSS) - coronavirus disease 2019 (hereafter, COVID-19). Tocilizumab (TCZ) was administered to these subjects, despite the lack of randomised clinical trial data. Hence, summarising data on the mortality rate and related risks factors may help physicians to correctly administer TCZ. METHODS: We performed a systematic review and meta-analysis on mortality rate in TCZ- treated patients with COVID-19 according to the PRISMA guidelines. The pooled mortality rate in TCZ-treated persons was calculated and meta-regressions were done to investigate associated factors. RESULTS: We included 22 studies and 1520 TCZ-treated patients (mean age: 61 years, 95% CI: 59-64; male: 71%, 95% CI: 64-78%). The mortality estimated pooled prevalence was 19% (95% CI: 13-25, I2=100%, p<0.00001) and improvement estimated pooled prevalence was 71% (95% CI: 62-81). Factors associated with the mortality are the number of patients in intensive care unit, the number of patients requiring invasive ventilation and the sera C-reactive protein value before TCZ administration. We observed a reduction in the odds of mortality in TCZ-treated patients when compared to those treated with other therapies (OR=0.47, 95% CI: 0.22-0.98, p=0.004). CONCLUSIONS: This study showed that the mortality pooled prevalence in TCZ-treated patients is lower than the overall mortality reported in patients with severe COVID-19.

Levels and Factors Associated with Resilience in Italian Healthcare Professionals during the COVID-19 Pandemic: A Web-Based Survey.

BACKGROUND: Resilience is defined as the capacity to cope successfully with change or adversity. The aims of our study were to investigate levels of resilience in Italian healthcare professionals (HCPs) during the Coronavirus disease 2019 (COVID-19) pandemic and to identify potential predictors of resilience. METHODS: We performed a web-based survey of HCPs (n = 1009) working in Italian hospitals during the COVID-19 pandemic. The survey contained a 14-item resilience scale (RS14) and questionnaires to evaluate depression and anxiety symptoms. Non-HCP individuals (n = 375) from the general population were used for comparison. RESULTS: HCPs showed significantly lower resilience compared to the control group (p = 0.001). No significant differences were observed after stratification for geographical area, work setting, role, or suspected/confirmed diagnosis of COVID-19. In a linear regression analysis, RS14 was inversely correlated with depression (R2 = 0.227, p < 0.001) and anxiety (R2 = 0.117, p < 0.001) and directly correlated with age (R2 = 0.012, p < 0.001) but not with body mass index (BMI, R2 = 0.002, p = 0.213). In male HCPs, higher depression score (odds ratio (OR) 1.147, p < 0.001) or BMI (OR 1.136, p = 0.011) significantly predicted having low resilience. In female HCPs, higher depression score (OR 1.111, p < 0.0001) and working in a COVID-19 free setting (OR 2.308, p = 0.002) significantly predicted having low resilience. HCPs satisfied with personal protective equipment had higher levels of resilience (p < 0.010). CONCLUSIONS: Our findings suggest that resilience was lower in Italian HCPs than in the general population after the first COVID-19 wave. Specific factors can be identified, and targeted interventions may have an important role to foster resilience of HCPs.

Rheumatic manifestations of COVID-19: a systematic review and meta-analysis.

BACKGROUND: Different proportions of musculoskeletal or autoimmune manifestations associated with COVID-19 have been reported in literature. We performed a systematic review and meta-analysis with the aim of assessing the prevalence of rheumatic manifestations in patients affected by COVID-19, as initial symptom or during disease course. METHODS: A database search was run on May 18th, 2020, using two distinct strategies. We were interested in the percentage of symptoms of potential rheumatologic interest observed in large population studies of COVID-19 cases, and in identifying uncommon autoimmune disorders described in patients with COVID-19. For manifestations individually reported, a meta-analysis was performed taking into consideration the proportion of COVID-19 patients presenting the symptom. RESULTS: Eighty eight original articles were included in the systematic review and 51 in the meta-analysis. We found pooled estimates of 19% for muscle pain and 32% for fatigue as initial symptom of COVID-19 presentation and, respectively, of 16 and 36% during the disease course. Only one article discussed arthralgia as unique symptom. Additionally, we found that vasculitis, chilblains, presence of autoantibodies commonly found in patients with rheumatic diseases, or autoimmune haematological and neurological disorders have all been reported in patients with COVID-19. CONCLUSIONS: In conclusion, our review and meta-analysis emphasises that symptoms potentially leading to rheumatologic referral are common in patients with COVID-19. Therefore, COVID-19 is a new differential diagnosis to bear in mind when evaluating patients with musculoskeletal symptoms and rheumatologists might play a crucial role in identifying COVID-19 cases in early phases of the illness.

Living with arthritis: a "training camp" for coping with stressful events? A survey on resilience of arthritis patients following the COVID-19 pandemic.

Resilience is defined as "the capacity of individuals to cope successfully with significant change or adversity". The challenge posed by the COVID-19 pandemic may potentially represent an overwhelmingly stressful event for patients with chronic diseases. Aim of our study was to investigate the levels of resilience in individuals with inflammatory arthritis living in Emilia Romagna, the third hardest-hit Italian region during the ongoing COVID-19 pandemic. To this purpose, we developed a survey consisting of four different sections assessing demographic characteristics, the 14-item resilience scale (RS14) and questionnaires evaluating depression and anxiety. Consecutive patients with inflammatory arthritis were recruited over a short time frame immediately after the end of national lockdown and compared with control individuals from the general population. One hundred twenty-two patients and 173 controls were included. Levels of resilience, as measured by RS14 score, were significantly higher in patients with inflammatory arthritis (82.6 ± 14.0 vs 79.0 ± 12.8, p = 0.018). After stratification for gender, the difference in RS14 score was maintained in women (p = 0.045), but not in men (p = 0.252). High resilience, defined as having a RS14 score > 90, was significantly more prevalent in patients than in controls (30% vs 16%, p = 0.009). In arthritis patients, no significant differences in RS14 were observed after stratification for specific diagnosis, age, or disease duration and activity. Our findings suggest that patients with inflammatory arthritis may be more resilient than the general population towards unexpected stressful events such as the ongoing COVID-19 pandemic. Key Points • Living with inflammatory arthritis may foster resilience. • After COVID-19, patients with inflammatory arthritis were more resilient than the general population.