ABSTRACT
Background: High disease activity, treatment with glucocorticoids (GC) and rituximab (RTX), have been related to worse outcomes of COVID-19. Objectives: To assess the clinical characteristics and severity of the SARS-CoV-2 infection in patients with rheumatoid arthritis (RA) included in the SAR-COVID registry and to identify factors associated with poor outcomes. Methods: SAR-COVID is a national, longitudinal and observational registry. Patients of ≥18 years old, with diagnosis of RA (ACR-EULAR criteria 2010) who had confrmed SARS-CoV-2 infection (RT-PCR or positive serology) were included between 13-8-20 and 31-7-21. Sociodemographic and clinical data, comorbidities, disease activity and treatment at the moment of the SARS-CoV-2 infection were collected. Additionally, infection symptoms, complications, medical interventions and treatments for COVID-19 were registered. Infection severity was assessed using the WHO-ordinal scale (WHO-OS)1. A cut-off value of ≥5 identifed patients with severe COVID-19 and those who died. Statistical analysis: Descriptive statistics. Chi2 or Fischer test, Student T test or Mann-Whitney and Kruskal Wallis or ANOVA, as appropriate. Multiple logistic regression model. Results: A total of 801 patients were included, with a mean age of 53.1 ± 12.9 years, most of them were female (84.5%) and the median (m) disease duration was 8 years (IQR 4-14). One third were in remission and 46.4% had comor-bidities, being the most frequent, hypertension (26.9 %), dyslipidemia (13.5 %), obesity (13.4 %) and diabetes (8.9%). Moreover, 3.2% had interstitial lung disease (ILD) associated with RA. At SARS-CoV-2 diagnosis, 42.5% were receiving glucocorticoids (GC), 73.9% conventional (c) disease modifying antirheumatic drugs (DMARD), 24% biologic (b) DMARD and 9.1% targeted synthetic (ts) DMARD. Among bDMARD, the most frequently used were TNF inhibitors (17%), followed by abatacept (2.8%), IL-6 inhibitors (2.4%) and rituximab (RTX) (2.1%). During the SARS-CoV-2 infection, 95.8% had symptoms, 27% required hospital-ization, 7.9% presented complications and 4.4% died due to COVID-19. Severe disease and death (WHO-OS≥5) was present in 7.5% of the patients. They were older (62.9±12.5 vs 52.2±12.7, p<0.001), and they had more frequently ILD (18.5% vs 2%, p<0.001), comorbidities (82.5% vs 43.7%, p<0.001), ≥2 comor-bidities (60.3% vs 25.8%, p<0.001), treatment with GC (61% vs 40.7%, p=0.04) and RTX (8.3% vs 1.6%, p=0.007). Conversely, the use of cDMARD and TNF inhibitors was more frequent in patients with WHO-OS<5, nevertheless this difference was not signifcant. Disease activity was comparable between groups. In multivariable analysis, older age, the presence of diabetes, ILD, the use of GC and RTX were signifcantly associated with WHO-OS≥5 (Figure 1). Furthermore, older age (65.7±10.8 vs 52.4±12.8, p<0.001), the presence of comor-bidities (87.9% vs 44.7%, p<0.001), chronic obstructive pulmonary disease (21.9% vs 5.2%, p=0.002), diabetes (30.3% vs 7.9%, p<0.001), hypertension (57.6% vs 25.6%, p<0.001), cardiovascular disease (15.6% vs 3.2%, p=0.005), cancer (9.1% vs 1.3%, p=0.001), ILD (23.3% vs 2.4%, p<0.001) and the use of GC (61.8% vs 41.4%, p=0.02) were associated with mortality. Older age [OR 1.1 IC95% 1.06-1.13] and the use of GC 5-10 mg/day [OR 4.6 IC95% 1.8-11.6] remained signifcantly associated with death due to COVID-19. Conclusion: Treatment with RTX and GC, as well as older age, the presence of diabetes and ILD were associated with poor COVID-19 outcomes in this national cohort of patients with RA. Older patients and those taking GC had a higher mortality rate.
ABSTRACT
Background: Persistent symptoms after acute COVID have been described previously. Main symptoms reported are fatigue, arthralgias, myalgias and mental sickness. Defnition and methods vary widely.1 Objectives: To asses prevalence and related factors to long COVID in a retrospective cohort of patients with rheumatic diseases from Argentina. Methods: A total of 1915 patients were registered from August 18th, 2020 to July 29th, 2021. Patients > 18 years old, with rheumatic disease and confrmed infection by SARS-CoV-2 (antigen or RT-PCR) were included. Those dead, with unknown outcome, wrong date or missing data were excluded. Demographic data, comorbidities, rheumatic disease, and characteristics of SARS-CoV-2 infection were recorded. Long COVID was defned according to NICE guidelines (persistent symptoms for more than 4 weeks, without alternative diagnosis). Long COVID symptoms were defned by rheumatologist. Severity of infection was clas-sifed according to WHO ordinal scale. We used descriptive statistics, univariate model (Student's test, chi square test, ANOVA) and multivariate logistic regression analysis. Results: 230 (12%) had long COVID. Median age was 51 (IQR 40-61]) years, 82% were females, 51% were not caucasian. Median of education was 13.3 years (IQR 12-16), 79 % had private health insurance and 55 % were employed. Nearly half (n=762, 46%) had comorbidities, the most prevalent was hypertension (n=396, 24%). The most frequent rheumatic diseases were rheumatoid arthritis (n=719, 42%) and systemic lupus ery-thematosus (n=280, 16 %). Most were in low activity/remission (79%), used Conventional DMARD (n=773 patients, 45%) and steroids (n=588, 34%) at low dose (n=415, 71%). Main laboratory findings were abnormal D-di-mer (n=94, 28%) and leukopenia (n=93, 26%). Most patients had a WHO ordinal scale < 5 (n=1472, 86%). Median of hospitalization at intensive care unit (ICU) was 8 days [IQR 5, 13]. Treatment for SARS-CoV-2 infection (steroids, anticoagulation, azithromycin, convalescent plasma) was used in 461 (27%) patients. Most of long COVID (n= 152, 69%) reported 1 symptom, the most frequent was fatigue (n= 55, 22%). Figure 1. Univariate analysis is presented in Table 1. In multivariate logistic regression analysis non-caucasian ethnicity OR 1.44 (1.07-1.95), years of education OR 1.05 (1-1.09), treatment with cyclophosphamide OR 11.35 (1.56-112.97), symptoms of COVID-19 OR 13.26 (2.75-242.08), severity scale WHO ≥ 5 OR 2.46 (1.68-3.57), and ICU hospitalization days OR 1.09 (1.05-1.14) were factors associated to long COVID. Conclusion: Prevalence of long COVID was 12%. Non-caucasian ethnicity, higher education, treatment with cyclophosphamide, symptoms of COVID-19, severe disease and ICU hospitalization days were related to long COVID.
ABSTRACT
Background: Visceral Leishmaniasis (VL) is a zoonotic infection produced by the Leishmania spp parasite transmitted through the bite of the Phlebotomus or Lutzomya mosquito. It is more frequent in endemic areas and a common, although underdiagnosed, cause of secondary hemophagocytic lymphohistiocytosis (HHL), consisting of a dysregulation of T lymphocytes and NK cells and uncontrolled macrophage activation. The generated cytokines storm (IFN-gamma, IL-1, 6, 10, 12, and 18) and uncontrolled hemophagocytosis result in a life-threatening hyperinflammatory state. The clinical-analytical manifestations between HLH and VL may overlap, making diagnosis difficult. Amphotericin B is the treatment of choice, together with corticosteroids and immunoglobulins in case of LHHs and no response to initial treatment. Aims: To express the importance of controlling the cytokine storm in Hemophagocytic Lymphohistiocytosis to avoid the development of the hyperinflammation state. Methods: Description of clinical case and sample of response to treatment with Tocilizumab. The follow-up was carried out until January 31, 2021. Results: A 51-year-old man with a personal history of psoriasis arthritis treated with Adalimumab and Methotrexate and cutaneous leishmaniasis on the pinna in February 2019, untreated. Consultation in the Emergency Service for a 2-week fever and general malaise, presenting progressive pancytopenia without remarkable findings in the peripheral blood smear. Viral serologies and PCR for SARS-CoV2 were negative;antigenuria for Leishmania was positive. Abdominal CT showed mild hepatomegaly and splenomegaly of 19 cm. Treatment is started with Liposomal Amphotericin B. The subsequent analytical study showed CRP 77.4 mg/L, IL-6 19.2 pg/mL, Ferritin> 4,500 ng/mL, triglycerides 217 mg/dL, AST/ALT 221/135 U/L and CD25s> 7500 U/mL. A bone marrow aspirate was performed which, together with a positive Leishmania PCR in peripheral blood and bone marrow and HScore with a probability of 94% HLH-2004 score with 6/8 items completed, LHHs to LV were diagnosed, adding Dexamethasone according to the HLH- 2004 protocol and Gammaglobulin. Despite the instaured measures, pancytopenia, fever> 38oC, liver involvement and hyperinflammatory status with IL-6 87.5 pg/mL persisted, deciding to administer a single dose of Tocilizumab 8 mg/Kg. The fever disappeared and the laboratory abnormalities were normalized in 1.5 months. Dexamethasone decrease was performed according to protocol. Currently Adalimumab has been restarted and continues with monthly doses of Amphotericin B. Summary/Conclusion: There is little scientific evidence about the targeted management of the cytokine storm generated in LHHs. Blocking the action of IL-6 with Tocilizumab at standard doses allowed adequate management of the pro-inflammatory state and the infection, without side effects and with good tolerance. Experience with Tocilizumab in LV LHHs is extremely limited. Understanding the pathophysiology of this entity and its similarity to other states of hyperactivation and immune dysregulation will allow better therapeutic regimens to be established. There is little scientific evidence about the targeted management of the cytokine storm generated in LHHs. Blocking the action of IL-6 with Tocilizumab at standard doses allowed adequate management of the pro-inflammatory state and the infection, without side effects. Experience with Tocilizumab in LV LHHs is extremely limited. Understanding the pathophysiology of this entity and its similarity to other states of hyperactivation and immune dysregulation will allow to establish better therapeutic regimens.