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

Abstract

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.

Public interest in musculoskeletal symptoms and disorders during the COVID-19 pandemic

“…In the initial period, internet searches for myalgia and toe swelling showed a significant increase. As myalgia is among the common symptoms of COVID-19 [23,24], this observation was not unexpected. Furthermore, the increase in toe swelling was probably related to media coverage of chilblains associated with COVID-19, called as "COVID toe" [25][26][27].…”

Circulating Calprotectin as a Biomarker of COVID-19 Severity

“…Several studies have linked COVID-19 with autoimmune conditions [54] such as anti-phospholipid syndrome [55][56][57][58][59][60], Guillain-Barré [61][62][63][64][65] and Miller Fisher syndromes [66,67] (reviewed in [68]). In addition, some patients with COVID-19 develop signs and symptoms that are also observed in certain autoimmune conditions [54,[69][70][71][72][73], but the number of patients reported to date tend to be small, lack immunoassay details and contemporaneous non-COVID-19 respiratory disease controls. A recent study reported autoantibodies to cytokines as a marker for disease severity in COVID-19 [74], which has interest because of previous associations of anticytokine antibodies to infectious disease susceptibility and outcomes.…”

Non-Respiratory Symptoms of Patients Infected with SARS-CoV-2 (Coronavirus Disease 2019): Lessons from Their Initial Presentation at the Hospital

“…Arthralgia is a serious and well-described clinical finding seen in many viral infections with a large number of causative agents reported [ 4 , 17 ]. However, arthralgia is often combined with myalgia, making it difficult to identify its overall prevalence [ 4 , 18 ]. Two studies, one single-centered and one multicenter cohort study, reported arthralgia as a unique symptom, indicating a prevalence of 2.5% in a total of 40 and 318 patients, respectively [ 17 , 19 ].…”