Metastatic sarcoma affecting the heart and presenting as infective endocarditis: about a single medical case (preprint)

Heart sarcomas are scarce neoplasms with various clinical features and are known to be great imitators of several clinical representations. This article presents a case of a cardiac metastatic sarcoma complicated by infective endocarditis in a 35-year-old female patient with a history of rheumatic fever, brain surgery, and Covid-19 infection. The diagnosis was based on echocardiography, computed tomography and biopsy results. Despite receiving six weeks of antibiotic treatment, the patient’s prognosis was bleak due to the lack of effective palliative options. The article underlines the challenges in the management of cardiac sarcomas and the need for further research in this field.

Genome-wide Association Study of Long COVID (preprint)

Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction(3-5). The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative(6,7) to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity(6), lung function(8), and cancers(9), suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.

Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.

Objectives: To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients. Methods: This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions. Results: There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1-25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08-0.26). Conclusions: SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.

Exploring the longer-term impact of the COVID-19 pandemic on physical and mental health of people with inflammatory rheumatic diseases: a cross-sectional survey.

OBJECTIVE: To assess the longer term impact of the COVID-19 pandemic on the self-reported physical and mental health of people with inflammatory rheumatic diseases (IRDs). METHODS: Two thousand twenty-four patients with IRDs were randomly selected from electronic health records. Survey invitations were sent (August 2021 coinciding with relaxation of UK COVID-19 restrictions) using SMS and postal approaches. Self-reported data included demographics, shielding status and physical (MSK-HQ) and mental health (PHQ8 and GAD7). RESULTS: Six hundred thirty-nine people completed the survey (mean (SD) age 64.5 (13.1) years, 384 (60%) female). Moderate/severe impact of the pandemic on physical and mental health was reported by 250 (41%) and 241 (39%) respectively. One hundred seventy-two (29%) reported moderate/severe depression (PHQ8 ≥ 10) and 135 (22%) moderate/severe anxiety (GAD7 ≥ 10). Females reported greater impacts of the pandemic on physical health (44% vs 34%), mental health (44% vs 34%), arthritis symptoms (49% vs 36%) and lifestyle factors (weight gain and reduced exercise and physical activity) than males. The physical and mental impacts were less in people with RA compared with other IRDs. Physical health impacts did not differ between age groups, but younger patients reported greater impacts on mental health. CONCLUSION: The COVID-19 pandemic has had a significant impact on the physical and mental health of people with IRDs. These effects were greatest in females. Recovery needs to address the negative impact of the pandemic on lifestyle factors to minimise the long-term impacts for people with IRDs. Key Points • The pandemic had a significant impact on long term physical and mental health in almost 40% of people with IRDs. • The impact of the pandemic was greater in women for physical health, mental health and arthritis symptoms. • Many people reported negative pandemic impacts on lifestyle factors including weight and physical activity.

Seroprevalence of SARS-CoV-2 antibodies in patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To assess the prevalence of anti-SARS-CoV-2 antibodies in autoimmune inflammatory rheumatic disease (AIIRD) patients, and to define clinical factors associated with seropositivity. METHODS: A cross sectional study was conducted at a tertiary rheumatology department in Israel. Consecutive patients completed a questionnaire and were tested for SARS-CoV-2 anti-nucleoprotein IgG (N-IgG). If this was positive, an anti-S1/S2 spike IgG (S-IgG) test was done. If both were positive, the patient was considered seropositive. Seropositive patients were retested after 3 months. RESULTS: The study included 572 AIIRD patients. Thirty patients were found seropositive, for a seroprevalence of 5.24%. The seropositive rate was significantly lower for patients treated with immunosuppressive medications (3.55%, p≤0.01), and specifically for patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) (2.7%, p≤0.05). These associations remained significant in the multivariate regressions adjusting for age, sex and exposure to a known COVID-19 patient. A second serology test 3 months later was collected in 21 of the 30 seropositive patients. In a mean±standard deviation (SD) of 166.63±40.76 days between PCR and second serology, 85% were still positive for N-IgG, and 100% were still positive for S-IgG, with a higher mean±SD titre compared to the first S-IgG (166.77±108.77 vs. 132.44±91.18, respectively, p≤0.05). CONCLUSIONS: Humoral response to SARS-CoV-2 in AIIRD patients may be affected be immunosuppressive treatment, especially bDMARDs. In patients with AIIRD, titres of SARS-CoV-2 IgG antibodies, especially N-IgG antibodies, fade with time, while S-IgG antibodies persist.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition (preprint)

Background: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥4 weeks and >12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of > 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p=0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p=0.5419). Regarding > 4 weeks post-acute COVID-19, frequencies of ≥3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p=0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p=0.1322). Further analysis of the risk factors for > 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p>0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p>0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

How Did the Two Years of the COVID-19 Pandemic Affect the Outcomes of the Patients with Inflammatory Rheumatic Diseases in Lithuania?

Background and objectives: the COVID-19 pandemic globally caused more than 18 million deaths over the period of 2020-2021. Although inflammatory rheumatic diseases (RD) are generally associated with premature mortality, it is not yet clear whether RD patients are at a greater risk for COVID-19-related mortality. The aim of our study was to evaluate mortality and causes of death in a retrospective inflammatory RD patient cohort during the COVID-19 pandemic years. Methods: We identified patients with a first-time diagnosis of inflammatory RD and followed them up during the pandemic years of 2020-2021. Death rates, and sex- and age-standardized mortality ratios (SMRs) were calculated for the prepandemic and pandemic periods. Results: We obtained data from 11,636 patients that had been newly diagnosed with inflammatory RD and followed up until the end of 2021 or their death. The mean duration of the follow-up was 5.5 years. In total, 1531 deaths occurred between 2013 and 2021. The prevailing causes of death in the prepandemic period were cardiovascular diseases, neoplasms, and diseases of the respiratory system. In the pandemic years, cardiovascular diseases and neoplasms remained the two most common causes of death, with COVID-19 in third place. The SMR of the total RD cohort was 0.83. This trend was observed in rheumatoid arthritis and spondyloarthropathy patients. The SMR in the group of connective-tissue diseases and vasculitis was higher at 0.93, but did not differ from that of the general population. The excess of deaths in the RD cohort during the pandemic period was negative (-27.2%), meaning that RD patients endured the pandemic period better than the general population did. Conclusions: The COVID-19 pandemic did not influence the mortality of RD patients. Strict lockdown measures, social distancing, and early vaccination were the main factors that resulted in reduced mortality in this cohort during the pandemic years.

Outcomes of Filipinos with inflammatory rheumatic diseases developing COVID-19 prior to vaccinations and new variants: a historical perspective.

We described the profile and outcome of Filipino patients with inflammatory rheumatic diseases (IRDs) who developed COVID-19 (IRD-C19) during the onset of the pandemic, prior to vaccinations and variants. We obtained de-identified data of Filipino patients with IRD-C19 from the Global Rheumatology Alliance registry from March 2020 to August 2021. Descriptive statistics and multivariate analyses were applied. Registered were 164 patients (mean age 44 years; 70% female). The most common IRDs were systemic lupus erythematosus (SLE, 41.4%), rheumatoid arthritis (RA, 15.2%), and gout (14.6%). Majority were receiving conventional DMARDs (59.1%) and/or glucocorticoid therapy (GC, 51.2%). Half (58.5%) were hospitalized, with risk higher in active IRD (OR 3.7), heart disease (8.52), and hypertension (8.73); and lower in SLE patients (0.15). Among hospitalized patients, 76% needed supplemental oxygen. Heart disease (6.28), hypertension (7.6), and moderate-to-high IRD activity (3.37) were associated with higher odds of requiring oxygen supplementation. Hypertension was associated with mechanical ventilation (8.23). Twenty-four (15%) patients died, with odds lower if on prednisone ≥ 10 mg/day (0.17) and with other autoimmune IRDs aside from SLE and RA (0.05). Among patients with IRD-C19 prior to vaccinations and variants, higher disease activity, hypertension, and heart disease were associated with poorer outcomes. Prednisone ≥ 10 mg/day was associated with lower odds of death. This study provides valuable historical information, emphasizing the need for continued data collection to clarify COVID-19's impact.

Safety and immunogenicity of the second and third doses of COVID-19 vaccine in adolescents with rheumatic diseases (preprint)

Background: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRD) compared with healthy controls. Methods: This international prospective study included adolescents with AIIRD and controls vaccinated with two (AIIRD n=124; controls n=80) or three (AIIRD n=64; controls n=30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titres in a sample from both groups. Results: The vaccination safety profile was favourable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable among 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p=0.55), which declined within 6 months to 87% and 100%, respectively (p=0.3), and increased to 100% in both groups, after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n=59) and 35% (n=28), respectively; p=0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p=0.1555). Conclusion: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with an adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRD against COVID-19.

Immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases.

Progress has been made in COVID-19 vaccine development, with encouraging safety and efficacy data. The purpose of this study was to investigate the immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Patients with AIIRD (n = 101) were included in this study. All patients received 2 doses of inactivated COVID-19 vaccine. Serum anti-S1/RBD protein IgG was detected 2-16 weeks after the second vaccination. Seropositivity was defined as IgG ≥ 1.00 bound antibody unit S/CO. Immunogenicity of inactivated COVID-19 vaccine was assessed by seropositivity rate and the levels of serum IgG antibody against anti-S1/RBD protein, compared with the general population (n = 46). There was no difference by statistical significance in the seropositivity rate between patients with AIIRD (82.2%) and SLE (86.1%) and the control group (93.5%), p > 0.05. The level of anti-S1/RBD protein IgG antibodies in patients with AIIRD (median [IQR], 8.8 [2.2-17.3]) and SLE (median [IQR], 9.6 [2.4-20.4]) was comparable to that in the control group (median [IQR], 7.2 [3.1-14.2]), p > 0.05. Patients treated with glucocorticoids(GCs) (median dose, [IQR]: 2.5 mg/day [IQR 2.5-5.0]) or hydroxychloroquine(HCQ) or GCs + HCQ without other immunomodulatory medications, had an appropriate immunogenic response(88.1%) with high levels of anti-S1/RBD protein IgG(median [IQR], 12.1 [6.5-20.4]). Neither of patients treated with rituximab had positive serum antibodies, which was statistically significant, compared with the control group (p < 0.01). Compared with the control group, methotrexate(MTX) and iguratimod(IGU) was significantly reduced the level of anti-S1/RBD protein IgG antibodies. Inactivated COVID-19 vaccine had appropriate immunogenicity in patients with AIIRD. Immunogenicity of inactivated COVID-19 vaccine was severely impaired by rituximab, and also suppressed by MTX and IGU, while low doses of GC and HCQ had negligible effect.

Changes in the frequency and clinical features of acute rheumatic fever in the COVID-19 era: a retrospective analysis from a single center.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) pandemic resulted in significant changes in the frequency of many diseases. In this study, we aimed to investigate the changes in the frequency and clinical features of acute rheumatic fever (ARF) in this period and determine the effect of health measures taken against COVID-19 on this change. METHODS: The cases with initial attack of ARF between January 2016 and March 2022 in Ataturk University, Division of Pediatric Cardiology, were determined from the clinic's database, and case per month ratios were calculated for each period, retrospectively. Also the frequency of the clinical manifestations was compared among patients before and during the outbreak. RESULTS: Frequency of the major clinical manifestations among patients before and during the outbreak was similar. On average, the number of cases reported per month in the years 2016, 2017, 2018, and 2019 are, respectively, 1.75, 2, 2.25, and 2.58. In the first 3 months of 2020, the average number of cases reported per month was 3.67. After the advent of the pandemic, in the period from April to December 2020 and from January to September 2021, an average of 0.56 and 0.22 cases were reported per month, respectively. The frequency of clinical features between patients diagnosed before and during the outbreak was similar. CONCLUSIONS: Our results indicated an important decrease in frequency of ARF, but no change in the clinical features of the disease during the COVID-19 pandemic. It is thought that this is the result of health measures taken for COVID-19. Children with an increased risk of acute rheumatic fever should be encouraged in terms of wearing mask, social distance, and cleaning, especially during the seasons when upper respiratory tract infections are common. Thus, a permanent decrease in the incidence of ARF and its recurrences may be achieved.

Evaluation of a Community-Led Program for Primordial and Primary Prevention of Rheumatic Fever in Remote Northern Australia.

Environmental factors including household crowding and inadequate washing facilities underpin recurrent streptococcal infections in childhood that cause acute rheumatic fever (ARF) and subsequent rheumatic heart disease (RHD). No community-based 'primordial'-level interventions to reduce streptococcal infection and ARF rates have been reported from Australia previously. We conducted a study at three Australian Aboriginal communities aiming to reduce infections including skin sores and sore throats, usually caused by Group A Streptococci, and ARF. Data were collected for primary care diagnoses consistent with likely or potential streptococcal infection, relating to ARF or RHD or related to environmental living conditions. Rates of these diagnoses during a one-year Baseline Phase were compared with a three-year Activity Phase. Participants were children or adults receiving penicillin prophylaxis for ARF. Aboriginal community members were trained and employed to share knowledge about ARF prevention, support reporting and repairs of faulty health-hardware including showers and provide healthcare navigation for families focusing on skin sores, sore throat and ARF. We hypothesized that infection-related diagnoses would increase through greater recognition, then decrease. We enrolled 29 participants and their families. Overall infection-related diagnosis rates increased from Baseline (mean rate per-person-year 1.69 [95% CI 1.10-2.28]) to Year One (2.12 [95% CI 1.17-3.07]) then decreased (Year Three: 0.72 [95% CI 0.29-1.15]) but this was not statistically significant (p = 0.064). Annual numbers of first-known ARF decreased, but numbers were small: there were six cases of first-known ARF during Baseline, then five, 1, 0 over the next three years respectively. There was a relationship between household occupancy and numbers (p = 0.018), but not rates (p = 0.447) of infections. This first Australian ARF primordial prevention study provides a feasible model with encouraging findings.

Revisiting QT prolongation in acute rheumatic fever - Relevance for hydroxychloroquine treatment.

In-vitro evidence suggests hydroxychloroquine could be a potential immunomodulator for the inflammatory carditis of acute rheumatic fever (ARF). Hydroxychloroquine used as an anti-inflammatory agent has a low side effect profile but its use in the Covid-19 pandemic raised concerns about QTc interval prolongation and cardiac arrhythmias. The prolongation of QTc in ARF appears benign but has not been widely studied. We aim to report QTc intervals in a contemporary ARF population and consider implications for hydroxychloroquine use in ARF. The study cohort was 197 children <15 years of age with a clinical diagnosis of ARF. The QTc mean (SD) was 445 msec (28), range 370-545 msec. Eighteen percent of the cohort had a QTc > 99th percentile for normal by age and 8 patients (4%) had a QTc over 500 msec. There was no difference of QTc by age or gender. Inter-observer repeatability for QTc (n = 33) was 35 msec. The QTc is often prolonged in the early phase of ARF, meaning that QT prolonging medications should be used with caution in this setting. Serial ECG monitoring of the QT interval is recommended if hydroxycholoroquine is used in ARF.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab (preprint)

Objectives Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy show substantially impaired anti-SARS-CoV-2 vaccine humoral but partly inducible cellular immune responses. However, the complex relationship between antigen-specific B and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown. Methods Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) patients receiving RTX, 12 RA patients on other therapies and 30 healthy controls after SARS-CoV-2 vaccination with either mRNA or vector based vaccines. Results A minimum of 10 B cells/µL in the peripheral circulation was necessary in RTX patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX patients lacking IgG seroconversion showed reduced antigen-specific B cells, lower frequency of TfH-like cells as well as less activated CD4 and CD8 T cells compared to IgG seroconverted RTX patients. Functionally relevant B cell depletion resulted in impaired IFNγ secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients independently of IgG formation. Conclusions Patients receiving rituximab with B cell numbers above 10 B cells/µl were able to mount humoral and more robust cellular responses after SARS-CoV-2 vaccination that may permit optimization of vaccination in these patients. Mechanistically, the data emphasize the crucial role of co-stimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B and plasma cell differentiation.

Humoral response to Pfizer mRNA vaccine against SARS CoV2, in patients with autoimmune inflammatory rheumatic diseases and the impact on the rheumatic disease activity (preprint)

Abstract Background: The registration trials of mRNA vaccines against SARS CoV2 did not address patients with autoimmune inflammatory rheumatoid diseases (AIRD). Aims: To assess the humoral response to mRNA vaccine against SARS CoV2, in AIRD patients treated with immunomodulating drugs and the impact on AIRD activity. Methods: Consecutive patients treated at the rheumatology institute who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study, at their routine visit. The patients were invited for serology test 4-6 weeks after receiving the second dose of vaccine. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay Results: One hundred fifty-six consecutive patients (76% females) treated at a single rheumatology center (mean age (range) 59.1 (21-83) years), mean (range) disease duration 10.8 (1-55) years), were recruited to the study. Thirty-five percents of patients received conventional synthetic (cs)DMARDs only, 64% biological/targeted synthetic (b/ts) DMARDs, 34% received combined treatment with csDMARDs and b/tsDMARDs and 32% corticosteroids (mean dose(range) 5.8mg(2.5-20mg) prednisone). One hundred thirty-seven patients (88%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, range 58-29499). Nineteen (12%) patients had negative tests, 11/19 were treated with B cell depleting agents. The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The rheumatic disease remained stable in all patients. Conclusions: The vast majority of AIRD patients developed a significant humoral response following the administration of the second dose of the Pfeizer mRNA vaccine against SARS CoV2 virus. Only minor side effects were reported and no apparent impact on AIRD activity was noted.

Impact of Hydroxychloroquine Used as DMARD on SARS CoV-2 Tests and COVID-19 Evolution (preprint)

Objectives: Data remain scarce on the impact of long-term hydroxychloroquine (HCQ) treatment on infection with SARS CoV-2. Our aim was to analyse the data of COVID-19 patients with inflammatory rheumatic and musculoskeletal diseases (iRMD-COVID-19 patients), and to compare those receiving HCQ as disease-modifying anti-rheumatic drug (DMARD) with those not receiving the drug.Methods: From the French iRMD-COVID-19 cohort, data on COVID-19 in patients receiving HCQ were compared to those of patients not receiving HCQ at the time of infection. Matching criteria were age, gender, comorbidities, immunosuppressive treatment and use of nasopharyngeal PCR test.Results: Among the 871 patients, 71 treated with HCQ prior to COVID-19 were matched with and compared to 191 controls. There was no significant difference between cases and controls in terms of nasopharyngeal PCR-positive rate (85% vs 81%; absolute standardized difference = 6.0%), clinical symptoms, rate of hospitalization (33.8% vs 27.7%; OR=1.75 (0.86-3.56); p=0.12), rate of severe form (admission to intensive care unit/death) (11.3% vs 9.4%; OR=1.94 (0.69-5.41); p=0.21).Conclusions: In a cohort of patients with iRMD, treatment with HCQ as DMARD did not modify either the SARS-CoV-2 nasopharyngeal PCR-positive rate or the clinical presentation and did not reduce the occurrence of severe forms of SARS CoV-2 infection, compared to patients not receiving HCQ.Trial Registration: ClinicalTrials.gov (NCT04353609).Funding Statement: This study was not supported by research funding, but FAI2R is funded by the French Ministry of Social Affairs and Health (ministère des solidarités et de la santé).Declaration of Interests: The authors have no competing interests.Ethics Approval Statement: Under French law, ethics committee approval was not required. The study was performed in compliance with MR-004, received permission from Lille University Hospital, and was declared to the Commission Nationale de l’Informatique et des Libertés (reference DEC20-107).