ABSTRACT
Background: COVID-19 runs a variable course resulting in acute respiratory distress syndrome and death in a subset of patients. The entry of SARS-CoV-2 into the cell stimulates innate immunity including NLRP3 inflammasome and lead to development of adaptive immunity later. Hyperinflammatory response with the release of proinflammatory cytokines including IL-1β and IL-6 results in cytokine storm in some patients with a worse outcome. Colchicine acts on NLRP3 inflammasome and inhibits and IL-1 mediated inflammatory attacks in gout and familial Mediterranean fever (FMF) patients. Patients with inadequate response to colchicine may benefit from anti-IL-1 biologic agents such as anakinra and canakinumab. Recently, favourable effects of anakinra have been observed in COVID-19 patients with findings of cytokine storm. Objectives: We aimed to evaluate the impact of COVID-19 among refractory FMF patients followed-up in tertiary referral with the treatment of biologic agents and also document the course of COVID-19 in these patients. Methods: We searched out database of FMF patients to identify those using biologic agents (anti-IL-1, anti-IL-6 or anti-TNF) for colchicine-refractory FMF. We interviewed the patients using a standard questionnaire by phone call for symptomatic COVID-19 and evaluated those patients who described findings of COVID-19 further by their hospital records or inviting them to the hospital for additional investigations. Results: We identified 183 patients and contacted 106 of them by phone in May-October 2020. A history of symptomatic COVID-19 was documented in 7 FMF patients who were on a biologic agent. Six were on anti-IL-1 and one was on anti-TNF, and one of the patients was not taking his biologic agents for 1 year. All of 7 patients had a favourable outcome. All but 1 patient followed at home and none of them developed findings of cytokine storm, thromboembolism and secondary bacterial infection. Hospitalized patient did not require intensive care unit (ICU) support or mechanical ventilation, and he was not given additional anti-inflammatory medications. Conclusion: This series of refractory FMF patients with potentially higher inflammatory characteristics showed COVID-19 did not result in a worse outcome in those patients during the first phase of the pandemic, and none developed findings of cytokine storm. Observations in these patients supports further that biologic agents blocking IL-1 and possibly TNF may contribute to the uneventful course of COVID-19 by preventing the development of hyperinflammatory response. Data collection from a larger group of patients, especially those with amyloidosis, will clarify the protective effects of colchicine and contribution of anti-IL-1 treatments on the favourable disease course during the second phase of the pandemic.
ABSTRACT
Background: The negative impact of COVID-19 in patients with ANCA associated vasculitis (AAV) and patients on rituximab (RTX) treatment have been reported (1). Risk factors for severe course of COVID-19 and increased mortality in these patients are unclear. Objectives: To evaluate the course of COVID-19 in our AAV cohort and identifying risk factors for mortality. Methods: Patients with AAV who were classified according to CHCC and whose scheduled last visit were after December 2019 were screened and evaluated for COVID-19 either by phone call or in the clinic. Records of patients with a history of hospital admission due to COVID-19 were evaluated. Cumulative clinical findings and treatment history were noted. Hypogammaglobulinemia (hIgG) was defined as IgG level below 700 mg/dl. All inpatients with a diagnosis of COVID-19 were screened for hIgG and IVIG was administered if necessary. Results: Eighty-nine patients (47.2% female, mean age 56 + 12.5 (28-81)) were included into the study. The diagnosis was GPA in 56 (62.9%) and MPA in 33 (37.1%) patients. Mean follow up time was 91 + 53.4 (26-272) months. Anti-PR3 and anti-MPO were positive in 46 (51.7%) and 32 (35.9%) patients, respectively. Lower respiratory tract (LRT) involvement was present in 72 (80.9%) and 10 patients had a history of diffuse alveolar haemorrhage (DAH). Sixty-one patients (68.2%) had a history of rapidly progressive glomerulonephritis (RPGN) and 21 (23.6%) had peripheral nervous system (PNS) involvement. Fifteen (16.9%) patients had COVID-19;14 of them were PCR positive, one patient had symptoms and thorax CT findings compatible with COVID-19. Pulmonary infiltrates were observed in 13 patients (86.7%);9 (60%) had severe pneumonia. Twelve patients (85.7%) were hospitalized, 6 patients (42.9%) needed ICU admission and 5 patients (35.7%) died. Tocilizumab and anakinra for hyperinflammation during COVID-19 were used in 1 (6.7%) and 4 (26.7%) patients, respectively. Four out of five deceased patients (3 on RTX treatment, 1 with renal transplant) were in remission at the time of COVID-19. COVID-19 was detected in a patient with disease flare and DAH, during treatment with high dose steroids and plasmapheresis. hIgG was detected in all deceased patients from COVID-19 during hospital admission (mean IgG: 495±113.2 mg/dL). Symptomatic COVID-19 was more frequent in patients with a history of DAH, RPGN and hIgG. hIgG during the follow-up was significantly associated with COVID-19 in multivariable analysis (p=0.01, OR=20,6 %95 CI (2-210). Comparison of patients who died of COVID-19 and survived showed that female sex, PNS involvement and hIgG during the clinical course and hospital admission were risk factors for increased mortality (Table 1). Age, smoking, treatments, history of flares or serious infections, remission status and chronic renal insufficiency did not differ between groups. Conclusion: The frequency and mortality from COVID-19 is found to be high in our AAV cohort compared to previous reports (1). Patients with serious lung or renal involvement are prone to symptomatic COVID-19. Previously reported severe outcomes on RTX therapy might be related to consequent hIgG. High dose IVIG treatment may not be sufficient in improving survival in AAV patients with severe COVID-19 and hIgG.
ABSTRACT
Background: Infection is a remarkable cause of morbidity and mortality in patients with SLE. Objectives: We aimed to determine the clinical course of COVID-19 infection in our patients with SLE and the factors affecting this course Methods: SLE patients (2012 SLICC criteria) diagnosed with COVID-19 infection by a positive PCR test and/or typical findings of lung involvement in CT (computed tomography) imaging were included. Data regarding cumulative clinical and laboratory characteristics, histopathology results, autoantibody profiles, immunsuppressives and damage (SLICC damage index/SDI)) were retrieved from the existing database and revised. SLE Disease Activity Index (SLEDAI-2K) was determined at the time of infection. Results: Sixteen SLE patients with COVID-19 infection were identified. Most (87.5%) of these patients were female. Seventy % (n=11) had lupus nephritis. Twenty-five % had thrombotic antiphospholipid syndrome. PCR was positive in 70% (n=11) of the patients. Pulmonary parenchymal findings compatible with COVID-19 were observed in 56% (n=9) of those patients. Regarding complaints upon admission, 50% (n=8) had fever, 44% (n=7) cough, 44% (n=7) dyspnea, 19% (n=3) myalgia, 12.5% (n=2) headache, 12.5% (n=2) nausea /vomiting, 6% (n=1) diarrhea, and 6 % (n=1) had anosmia. Eight patients were hospitalized. Six of these patients needed oxygen therapy via nasal cannula. None needed a follow-up in the intensive care unit. The mean hospitalization duration was 14 ± 5 (8-25) days. Regarding disease activity at the time of infection, 9 had inactive disease with a SLEDAI-2K score of 0 whilst in 5 patients SLEDA-2K score was ≥4. The mean SLEDAI-2K score at the time of infection was 1.7 ± 2.3 (0-6). System/ organwise, 1 patient with chronic thrombocytopenia presented with a worsening platelet count accompanied by serologic activity. This patient was a non-adherent to treatment who had stopped taking mycophenolic acid months before COVID19. Three patients 2 of whom had proliferative nephritis experienced nephritic flares.1 patient who had a history of cutaneous lupus and was in remission presented with oral ulcer, leukopenia and hypocomplementemia during infection. Of 16 patients, 7 had system damage at the time of infection. The mean SDI score of the patients was 1.4±1.8. Comparison of patients with and without damage revealed no significant differences in disease activity, symptoms associated with COVID, in the need for hospitalization, hospitalization duration, and the requirement for oxygen therapy. However,CT findings compatible with COVID19, were more common in patients with damage (87% vs.33%,p=0.04) and their mean CRP levels were higher at diagnosis (65 ± 47 vs.22 ± 48 mg/l;p=0.032). All patients received similar treatment for COVID-19 except active patients who required high dose steroids (2 with active renal, 1 with thrombocytopenia and 1 with oral ulcer, leukopenia and hypocomplementemia).The patient with thrombocytopenia also received intravenous immunoglobulin and 1 with cutaneous active disease received tocilizumab as she developed macrophage activation syndrome. Six patients (37.5%) had received rituximab (RTX) in the last 6 months before COVID. No significant difference, in terms of hospitalization and need for oxygen therapy due to COVID19 was found between patients who had received RTX vs who had not. No hypogammaglobulinemia was detected in patients who received RTX despite lower levels of IgG (998 ± 184 vs 1481± 51 mg/dl, p=0.02) Conclusion: Although half of the patients in our series of COVID19 infected SLE patients required hospitalization, there were no mortalities. More patients with damage (none pulmonary) displayed CT findings compatible with COVID19 and further follow up will reveal whether they will suffer from fibrotic lung disease. Patients can experience disease flares during COVID. But it is also important to consider that some manifestations such as thrombocytopenia may also be a sign of severe infection. Immunosupressive agents may not have a negative impact on the course of infection.