Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Frequency and severity of COVID-19 in patients with various rheumatic diseases treated regularly with colchicine or hydroxychloroquine.

This study aimed to investigate whether patients regularly using colchicine or hydroxychloroquine (HCQ) have an advantage of protection from coronavirus disease 2019 (COVID-19) or developing less severe disease. Patients who were taking colchicine or HCQ regularly for a rheumatic disease including Familial Mediterranean Fever, Behçet's syndrome, Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Sjogren's syndrome, as well as their healthy household contacts as the control group, were included in the study. The clinical data regarding COVID-19 were collected using a standard form, and serum samples were analyzed for anti-severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) nucleocapsid immunoglobulin G (IgG). A total of 635 regular colchicine users with their 643 household contacts and 317 regular HCQ users with their 333 household contacts were analyzed. Anti-SARS-COV-2 IgG was positive in 43 (6.8%) regular colchicine users and 35 (5.4%) household contacts (odds ratio [OR] = 1.3; 95% confidence interval [CI]:0.8-2; p = 0.3). COVID-19-related symptoms were described by 29 (67.4%) of the patients and 17 (48.6%) household contacts (OR = 2.2; 95% CI :0.9-5.5; p = 0.09), and hospital admission was observed in five (11.6%) and one (2.9%) of these subjects (OR = 4.5; 95% CI: 0.5-40.2; p = 0.1), respectively. Seropositive subjects were observed in 22 (6.9%) regular HCQ users and 24 (7.2%) household contacts (OR = 1.1; 95% CI: 0.6-1.9; p = 0.8). COVID-19-related symptoms occurred in 16 (72.7%) of the 22 patients and 12 (50%) of 24 household contacts (OR = 2.7; 95% CI: 0.8-9.1; p = 0.1). Three patients (13.6%) were admitted to hospital, while one household contact (4.2%) was hospitalized (OR = 3.6; 95% CI: 0.3-37.8; p = 0.2). Being on a regular treatment of colchicine or HCQ did not result in the prevention of COVID-19 or amelioration of its manifestations.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.