Idiopathic inflammatory myopathies linked to vaccination against SARS-CoV-2: a systematic review.

The COVID-19 pandemic represents a global health problem, which has been mitigated by the opportune introduction of vaccination programs. Although we already know the benefit that vaccines provide, these are not exempt from adverse events which can be mild to deadly, such as idiopathic inflammatory myopathies, in which a temporal association has not been defined. It is for this reason that we carried out a systematic review of all reported cases of vaccination against COVID-19 and myositis. To identify previously reported cases of idiopathic inflammatory myopathies associated with vaccination against SARS-CoV-2 we registered this protocol on the website of PROSPERO with identification number CRD42022355551. Of the 63 publications identified in MEDLINE and 117 in Scopus, 21 studies were included, reporting 31 cases of patients with vaccination-associated myositis. Most of these cases were women (61.3%); mean age was 52.3 years (range 19-76 years) and mean time of symptom onset post-vaccination was 6.8 days. More than half of the cases were associated with Comirnaty, 11 cases (35.5%) were classified as dermatomyositis, and 9 (29%) as amyopathic dermatomyositis. In 6 (19.3%) patients another probable trigger was identified. Case reports of inflammatory myopathies associated with vaccination have heterogeneous presentations without any specific characteristics: as a consequence, it is not possible to ensure a temporal association between vaccination and the development of inflammatory myopathies. Large epidemiological studies are required to determine the existence of a causal association.

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study.

OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.

Incidence, features, and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: Vaccination against coronavirus disease 2019 (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM); however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features, and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. METHODS: A cohort of 176 IIM patients were interviewed after the third wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). RESULTS: A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 mo, and 13/146 (8.9%) patients within 1 mo. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30 ± 15.81; seven minor, five moderate, and zero major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1 ± 19.53; 3 minimal, 8 moderate, and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p < .0001; odds ratio, 33; confidence interval, 9-120) was significantly associated with the occurrence of a relapse. DISCUSSION: A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare.

Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death. RESULTS: Of 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively). CONCLUSIONS: This is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.

COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: Vaccine safety in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In this study we investigated COVID-19 vaccination-related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs). METHODS: Seven-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics were obtained and multivariable regression was performed. RESULTS: Ten thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30-455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04-7.3) and minor (OR, 1.5; IQR, 1.1-2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2-4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1-3.3; and OR, 2.2; IQR, 1.1-4.3, respectively). Overall, ADEs were less frequent in inclusion-body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients. DISCUSSION: Seven-day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs. Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines.

Relapses of idiopathic inflammatory myopathies after vaccination against COVID-19: a real-life multicenter Italian study.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination plays a crucial role as pivotal strategy to curb the coronavirus disease-19 (COVID-19) pandemic. The present study described the clinical status of patients affected by idiopathic inflammatory myopathies (IIM) after COVID-19 vaccination to assess the number of relapses. We included all patients affected by IIM and followed by Myositis Clinic, Rheumatology and Respiratory Diseases Units, Siena University Hospital, Bari University Hospital, Policlinico Umberto I, Sapienza University, Rome, and Policlinico Paolo Giaccone, Palermo. They underwent a telephone survey. A total of 119 IIM patients (median, IQR 58 (47-66) years; 32males; 50 dermatomyositis, 39 polymyositis and 30 anti-synthetase syndrome) were consecutively enrolled. Except four patients who refused the vaccination, 94 (81.7%) received Comirnaty, 16 (13.9%) Spikevax, 5 (4.4%) Vaxzevria. Seven (6.1%) patients had flare after vaccination. One of them had life-threatening systemic involvement and died two months after second dose of COVID-19 vaccination. From logistic regression analysis, Chi2-log ratio = 0.045,the variable that most influences the development of flare was the number of organs involved (p = 0.047). Sixty-eight patients received the third dose of COVID-19 vaccination: 51(75%) Comirnaty and 17 (25%) Moderna. No patients had flares after third dose. Our study represents the largest cohort of IIM patients in which the incidence of recurrence after anti-SARS-CoV-2 vaccine was assessed. In line with real-life data from other diseases, we found a clinical non-statistically significant risk of relapse in our patients, which occurred seldom, usually mild and in patients with a more severe and aggressive course of disease.

A systematic review and meta-analysis of mycobacterial infections in patients with idiopathic inflammatory myopathies.

OBJECTIVES: Infections including tuberculosis (TB) are a leading cause of morbidity and mortality in idiopathic inflammatory myopathies (IIM). We systematically reviewed the prevalence of mycobacterial infections in patients with IIM. METHODS: We screened PUBMED, EMBASE and SCOPUS databases and conference abstracts (2015-20) for original articles using Covidence. Pooled estimates of prevalence were calculated. RESULTS: Of 83 studies (28 cohort studies, two case control and 53 case reports), 19 were analysed. Of 14 043 IIM patients, DM (54.41%) was the most common subset among TB. Most studies were from Asia with high prevalence (5.86%, 2.33%-10.60%). Pooled prevalence of mycobacterial infections among IIM was 3.58% (95% CI: 2.17%, 5.85%, P < 0.01). Disseminated and extrapulmonary forms (46.58%; 95% CI: 39.02%, 54.31%, P = 1.00) were as common as pulmonary TB (49.07%; 95% CI: 41.43%, 56.75%, P =0.99) both for I2=0. Muscle involvement, an otherwise rare site, was frequently seen in case reports (24.14%). M. tuberculosis (28.84%) was the most common pathogen followed by Mycobacterium avium complex (3.25%). Non-tuberculous mycobacteria were less common overall (6.25; 95% CI: 3.49%, 10.93%) I2=0, P =0.94. Subgroup analysis and meta-regression based on high vs low TB regions found prevalence 6.61% (2.96%, 11.33%) in high TB regions vs 2.05% (0.90%, 3.56%) in low TB regions. While death due to TB was occasionally reported (P =0.82), successful anti-tubercular treatment was common (13.95%). CONCLUSION: TB is common in IIM, particularly in endemic regions though current data is largely heterogeneous. Extra-pulmonary forms and atypical sites including the muscle are frequent. Limited data suggests fair outcomes, although larger prospective studies may offer better understanding.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

Monitoring disease activity and damage in adult and juvenile idiopathic inflammatory myopathy.

PURPOSE OF REVIEW: We have reviewed the literature to identify significant advances related to disease activity and damage in the idiopathic inflammatory myopathies (IIMs) from January 2019 to July 2020. RECENT FINDINGS: New observations in the field from 2019 to 2020 have resulted in a better understanding of the clinical association and pathogenic origins of IIM. The use of patient-reported outcome measures and perspectives, identifying biomarkers and making better use of autoantibody testing are summarized. Basic sciences have led to an improved understanding of the role of NETosis in calcinosis, and of interferon type 1, in IIM. Preliminary insights are offered into Covid-19 in the setting of IIM, and the use of potential tools for monitoring disease remotely, which may assume larger importance for optimal disease management during a global pandemic. The wider exploration of newer imaging modalities and the use of nailfold capillaroscopy is a further step in better management of the condition. SUMMARY: The summarized research in IIM is a step forward in being able to further define, and to distinguish disease activity from damage, in order to potentially aid future clinical diagnosis and management in this challenging disease.

COVID-19 and the nervous system.

A pandemic due to novel coronavirus arose in mid-December 2019 in Wuhan, China, and in 3 months' time swept the world. The disease has been referred to as COVID-19, and the causative agent has been labelled SARS-CoV-2 due to its genetic similarities to the virus (SARS-CoV-1) responsible for the severe acute respiratory syndrome (SARS) epidemic nearly 20 years earlier. The spike proteins of both viruses dictate tissue tropism using the angiotensin-converting enzyme type 2 (ACE-2) receptor to bind to cells. The ACE-2 receptor can be found in nervous system tissue and endothelial cells among the tissues of many other organs.Neurological complications have been observed with COVID-19. Myalgia and headache are relatively common, but serious neurological disease appears to be rare. No part of the neuraxis is spared. The neurological disorders occurring with COVID-19 may have many pathophysiological underpinnings. Some appear to be the consequence of direct viral invasion of the nervous system tissue, others arise as a postviral autoimmune process, and still others are the result of metabolic and systemic complications due to the associated critical illness. This review addresses the preliminary observations regarding the neurological disorders reported with COVID-19 to date and describes some of the disorders that are anticipated from prior experience with similar coronaviruses.