Association of Programmed Cell Death 1 (PD-1) Gene Polymorphism (rs10204525) With COVID-19 Severity and Mortality: A Case-Control Study in the Iranian Population

Background Programmed cell death 1 (PD-1), as a negative immune regulator, regulates the activation of T cells and maintains the immune system's homeostasis. Previous studies suggest that the effective immune response against COVID-19 contributes to the outcome of the disease. The present study aims to evaluate whether the PD-1 rs10204525 polymorphism is associated with PDCD-1 expression and COVID-19 severity and mortality in the Iranian population. Methods the PD-1 rs10204525 was genotyped in 810 COVID-19 patients and 164 healthy individuals as a control group using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, we assessed the expression of PDCD-1 in peripheral blood nuclear cells by real-time PCR. Results Regarding disease severity and mortality, no significant differences were detected between study groups in alleles and genotypes frequency distribution under different inheritance models. We found that the expression of PDCD‐1 was significantly lower in COVID-19 patients with AG and GG genotypes than in the control group. Regarding disease severity, mRNA levels of PDCD‐1 were significantly lower in moderate and critical patients carrying AG genotype than in control (P=0.005 and P=0.002, respectively) and mild (P=0.014 and P=0.005, respectively) individuals. Additionally, the severe and critical patients with GG genotype displayed a significantly lower level of PDCD-1 compared with the control (P=0.002 and P<0.001, respectively), mild (P=0.004 and P<0.001, respectively), and moderate (P=0.014 and P<0.001, respectively) ones. Regarding disease mortality, the expression of PDCD‐1 was significantly lower in non-survivor COVID-19 patients with GG genotype than in survivors. Conclusion Considering the lack of significant differences in PDCD-1 expression in different genotypes in the control group, lower expression of PDCD-1 in COVID-19 patients carrying the G allele suggests the impact of this single-nucleotide polymorphism on the transcriptional activity of PD-1.

Outcomes of coronavirus disease 19 patients with a history of rheumatoid arthritis: A retrospective registry-based study in Iran.

BACKGROUND: We aimed to study the outcomes of coronavirus disease 2019 (COVID-19) in patients with a history of rheumatoid arthritis (RA) in Iran, where most patients receive corticosteroids and are at high risk for COVID-19 infection. METHOD: We collected the demographic, diagnostic, and treatment data of all COVID-19 patients by the clinical COVID-19 registry system. We recruited 38 RA patients and 2216 non-RA patients from the COVID-19 registry. The primary outcome was mortality due to COVID-19. We also studied the risk of intensive care unit admission and intubation in RA patients compared to non-RA patients. We used multiple logistic regression analysis to study the association between RA and the risk of COVID-19 outcomes. RESULT: We recruited 38 RA patients and 2216 non-RA patients from the COVID-19 registry. The RA patients had a higher mean age (59.9 years) than the non-RA patients (57.7 years). The group of RA patients had a larger proportion of women (76.3%) than the non-RA patients (40.8%). The death rate due to COVID-19 was significantly higher in RA patients than non-RA patients (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.24-5.81). The OR was higher among those who received prednisolone than among those who did not (OR = 3.59, 95% CI = 1.54-7.81). The odds of intubation were statistically significant among patients who received corticosteroid therapy (OR = 2.58, 95% CI = 1.07-6.18). CONCLUSION: The risk of COVID-19 outcomes was higher in RA patients than non-RA patients, especially for RA patients who received a low dose of prednisolone. The results of this study can be used to triage RA patients who get infected by COVID-19. Further studies with larger sample sizes are required to more precisely define the high-risk groups.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.

INTRODUCTION: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. METHODS: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population. RESULTS: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study. CONCLUSIONS: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.