ABSTRACT
Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.
ABSTRACT
Introduction: Patients with myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are at a high risk of severe SARS-CoV-2 infection. It is uncertain whether patients with AML and MDS, who frequently have quantitative or qualitative deficiencies of neutrophils and/or lymphocytes, will develop protective immunity from SARS-CoV-2 vaccines. The primary aim of this analysis was to describe the immune response and safety profile to the mRNA-1273 vaccine amongst a cohort of patients with AML and MDS. Methods: We enrolled AML and MDS patients to a large, single-site observational study of mRNA-1273 vaccination in cancer patients during the period January 12 to January 25, 2021. Blood specimens were collected from patients prior to the first and second vaccine doses (Days 1 and 29) and ~28 days after the second vaccine dose (Day 57) for antibody analyses. Retrospective chart review was done to collect information on baseline characteristics, cancer diagnoses, treatments received, and disease status. To evaluate serostatus, a two-step ELISA was performed, measuring IgG responses. SARS-CoV-2 antibody positivity rates were compared using the Fisher exact test or Chi-square test. The association of SARS-CoV-2 antibody titer and patient characteristics was examined by using Kruskal-Wallis test. Paired t-test was used to analyze the difference of SARS-CoV-2 antibody titers among day 1, after dose 1 and dose 2. Results: A total of 46 patients, 30 patients with AML and 16 patients with MDS, were included in this study. The median age at vaccination for the entire cohort was 68 yrs (range 37-85 yrs). The majority of patients were males (58.7%) and Caucasians (95.7%). Table 1 describes the baseline characteristics of the patients. The median time from diagnosis to the start of vaccination series was 24.3 months (range 4.5-105). One third of the patients (32.6%, n=15) were on active treatment for their disease during the course of vaccination with hypomethylating agents (n=6;13%), erythroid maturation agent i.e. luspatercept (n=2, 4.3%), immunomodulatory drugs i.e. lenalidomide (n=1;2.2%) and targeted therapy (6;13%). Targeted therapy included patients on enasidenib (n=4), midostaurin (n=1) and gilteritinib (n=1). A total of 32 patients (69.6%) were post allogeneic stem cell transplantation for their disease. The median time since allo-SCT for the entire cohort was 17 months (4.9-75.8 mos). The majority of the patients (n=40, 87%) were in remission at the time of vaccination. We found that two patients with AML relapsed post vaccination. Overall, 69.6% patients were seropositive at day 29 (after first vaccine dose) and 95.7% patients were seropositive on day 57 (after 2 vaccine doses). Table 2 describes response to the vaccine in our cohort and the differences in seropositivity rate after one and two doses of vaccine, based upon disease characteristics. Age, gender, race, disease status, time to vaccination from disease diagnosis, number of prior lines of therapy, whether on active treatment, laboratory parameters (including ALC and ANC), whether the patient had undergone allo-SCT, and therapy at time of vaccination did not significantly affect the seropositivity rate. Antibody titer levels were significantly higher after the 2 nd vaccine dose than after 1 st dose (mean 3806.5 vs 315, p<0.0001), a difference that was observed across the different variables and patient subsets (Figure 1). Mild injection site pain, fatigue, headache and arm swelling were the most common adverse events post vaccination. Conclusion: In this observational study, the largest reported to date amongst AML and MDS patients with serial serologic data following 2 vaccine doses, we found that the vast majority of patients with AML and MDS converted to seropositivity after two doses of the vaccine. Although the overall sample size was relatively small, most clinical and laboratory variables (including neutropenia and lymphopenia) did not affect the seropositivity rate. Antibody titer levels increased dramatically follo ing the 2 nd vaccine dose, indicating the potential utility for serial vaccination (i.e. additional dosing) in poorly-responsive patients. While these findings should be substantiated in a larger cohort, mRNA-273 SARS-CoV-2 vaccine appears to induce a strong humoral response in this population of patients with AML and MDS. [Formula presented] Disclosures: Komrokji: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees;Geron: Consultancy;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Acceleron: Consultancy;Jazz: Consultancy, Speakers Bureau;Taiho Oncology: Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy;BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;AROG: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sallman: Incyte: Speakers Bureau;AbbVie: Membership on an entity's Board of Directors or advisory committees;Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Agios: Membership on an entity's Board of Directors or advisory committees;Intellia: Membership on an entity's Board of Directors or advisory committees;Kite: Membership on an entity's Board of Directors or advisory committees;Magenta: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Syndax: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy. Padron: Taiho: Honoraria;Kura: Research Funding;BMS: Research Funding;Blueprint: Honoraria;Incyte: Research Funding;Stemline: Honoraria. Kuykendall: BluePrint Medicines: Honoraria, Speakers Bureau;Abbvie: Honoraria;Celgene/BMS: Honoraria, Speakers Bureau;CTI Biopharma: Honoraria;Incyte: Consultancy;Novartis: Honoraria, Speakers Bureau;Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Prelude: Research Funding;PharmaEssentia: Honoraria. Giuliano: Merck & CO: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet: Daiichi Sankyo: Consultancy;BerGenBio: Consultancy;Celgene/BMS: Consultancy;Millenium Pharma/Takeda: Consultancy;Agios: Consultancy;ElevateBio Management: Consultancy;AbbVie: Consultancy;Astellas: Consultancy;Jazz: Consultancy.