Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.

The Effect of Exogenous Surfactant on Moderate and Severe Stages of COVID-19 Induced ARDS: the Pilot Study of a Clinical Trial.

COVID-19 pandemic has created a global health challenge. Many pharmaceuticals have been repurposed as potential treatments, though many have not been promising. Due to the inflammatory and destructive effects of the virus on alveolar cells, the effect of exogenous surfactant was assessed as a potential treatment of lung dysfunction in COVID-19 patients. In this pilot study of the clinical trial, 49 patients aged 35-80 years with COVID-19 admitted in ICU entered the study (22 patients intubated and 23 had face masks; 4 patients in the control arm). The treatment arm patients received two consecutive doses of surfactant. P/F ratio (based on serial blood gas analyses before and 12 hours after 2 doses of surfactant) and also, clinical outcomes were assessed.in COVID-19 adult patients, surfactant significantly improved pulmonary P/F ratio both in intubated and face mask COVID-19 patients (increasing from 119.2 ± 51.7 to 179.4 ± 115.5). The rate of extubation was much better than similar country-wide studies. Surfactant significantly alleviates the respiratory status in moderate to severe COVID-19 ARDS with two consecutive 100 mg doses of surfactant (with 6 hours' interval) though previous studies have been controversial, regarding the effect of surfactant in general forms of ARDS. Higher doses might have better effects, mandating more trials.

Development and validation of models for two-week mortality of inpatients with COVID-19 infection: A large prospective cohort study

Recognizing COVID-19 patients at a greater risk of mortality assists medical staff to identify who benefits from more serious care. We developed and validated prediction models for two-week mortality of inpatients with COVID-19 infection based on clinical predictors. A prospective cohort study was started in February 2020 and is still continuing. In total, 57,705 inpatients with both a positive reverse transcription-polymerase chain reaction test and positive chest CT findings for COVID-19 were included. The outcome was mortality within 2?weeks of admission. Three prognostic models were developed for young, adult, and senior patients. Data from the capital province (Tehran) of Iran were used for validation, and data from all other provinces were used for development of the models. The model Young, was well-fitted to the data (p?<?0.001, Nagelkerke R2 = 0.697, C-statistics = 0.88) and the models Adult (p?<?0.001, Nagelkerke R2 = 0.340, C-statistics = 0.70) and Senior (p?<?0.001, Nagelkerke R2 = 0.208, C-statistics = 0.68) were also significant. Intubation, saturated O2?<?93%, impaired consciousness, acute respiratory distress syndrome, and cancer treatment were major risk factors. Elderly people were at greater risk of mortality. Young patients with a history of blood hypertension, vomiting, and fever;and adults with diabetes mellitus and cardiovascular disease had more mortality risk. Young people with myalgia;and adult patients with nausea, anorexia, and headache showed less risk of mortality than others.

Exposure to sulfur mustard increases the risk for mortality in patients with COVID-19 infection: A cohort study.

OBJECTIVE: This study aims to assess the prognosis of inpatients with COVID-19 infection who have a history of sulfur mustard exposure. METHODS: We started a cohort study in October 2020 and ended in May 2021 on inpatients with COVID-19 infection who had been admitted to university healthcare centers. The analytic sample included 960 inpatients having COVID-19 infection (192 with; and 768 without sulfur mustard exposure). The exposed patients were male war veterans, and the unexposed patients were male individually age-matched people. All patients had a positive RT-PCR test and a positive chest CT for COVID-19. The outcome was death within 28 days of admission, and the predictors were clinical features recorded at patients' bedsides. RESULTS: There was a significantly higher prevalence for asthma (p = 0.026) and pulmonary disease other than asthma (p < 0.001) in patients with the exposure. Sulfur mustard exposure was associated with increased risk for mortality of COVID-19 [hazard ratio (95% CI) = 1.92 (1.14,3.24), p = 0.013]. Early intubation signified a poor prognosis [hazard = 7.34 (4.65,11.58), p < 0.001]. However, individuals with higher PaO2 [hazard = 0.97 (0.95,0.98), p < 0.001], or people undergoing O2 therapy early upon admission [hazard = 0.58 (0.38,0.89), p = 0.011] showed lower risks for mortality. Individuals with asthma were at higher risk for mortality [hazard = 3.76 (1.69,8.36), p = 0.001]. CONCLUSION: Individuals with COVID-19 infection and sulfur mustard exposure should be considered high-risk patients and that, healthcare settings should be ready to provide critical care for them, including O2 therapy. They are more likely to have asthma or other pulmonary diseases.

Risk Assessment of COVID-19 in the Iranian Health System.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has exerted unprecedented pressure on healthcare systems throughout the world. This study was designed to develop a national health emergency management program based on risk assessment for COVID-19. METHODS: Mixed-methods research was used. Based on recommendations of the national epidemiology committee, 2 risk scenarios were used as basic scenarios for risk assessment. Two rounds of Focus Group Discussions (FGDs) were conducted between January and May 2020 with 30 representatives of the health system. The data were collected, analyzed, and integrated by the research team. RESULTS: In the risk matrix, "contamination of environment and individuals" and "burnout of medical staff" occupied the red zone (intolerable risk). "Defects in screening and admissions," "process disruption in medical care and rehabilitation," "increased mental disorders," "social dissatisfaction," "the decline in healthcare services," and "loss of medical staff" were identified as the orange zone (significant risk) of the matrix. CONCLUSIONS: The avoidance of environmental and individual contamination and healthcare worker burnout are the priorities in Iran. Attention to intersectoral cooperation, the involvement of non-governmental organizations and private center capacities, integration of information health systems, and developing evidence-based protocols are other measures that can improve the health system's capacity in the response COVID-19.

Anxiety and Depression in Health Workers and General Population During COVID-19 in IRAN: A Cross-Sectional Study.

BACKGROUND: The COVID-19 outbreak has exerted a great deal of psychological pressure on Iranian health workers and the general population. The aim of this study was to determine the effect of pandemic on anxiety and depression in Iranian population. METHODS: An online cross-sectional study was conducted for the general public and healthcare workers in Iran using a questionnaire comprised of demographic questions and Hospital Anxiety and Depression Scale. Chi-square test and univariate and multivariate logistic regression models were conducted. RESULTS: Of the 2045 participants, 1136 (65.6%) were considered to have moderate and severe anxiety symptoms, and 865 (42.3%) had moderate and severe depression symptoms. The prevalence of anxiety was higher in the females than in the males (OR = 1.4, 95% CI: 1.123-1.643, P = .002); the prevalence of anxiety was significantly higher in those aged 30-39 years than in other age-groups (OR = 1.6, 95% CI: 1.123-2.320, P = .001); furthermore, the prevalence of anxiety and depression was significantly higher in doctors and nurses compared with other occupations ((OR = 1.9, 95% CI: 1.367-2.491, P < .001) and (OR = 1.5, 95% CI: 1.154-2.021, P = .003)). In addition, the prevalence of anxiety symptoms in the likely infected COVID-19 group was higher than in the noninfected COVID-19 group (OR = 1.35, 95% CI: 1.093-1.654, P = .005). CONCLUSIONS: Regarding the high prevalence of anxiety and depression symptoms, especially among healthcare workers, appropriate psychological/psychiatric intervention necessitates.

The effect of surfactant on clinical outcome of patients with COVID-19 under mechanical ventilation: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Assessing the effect of surfactant on clinical outcome in patients with COVID-19 under mechanical ventilation TRIAL DESIGN: Single centre, two arm, parallel group (1:1 allocation ratio), randomised superiority trial with blinded care and outcome assessment. PARTICIPANTS: Inclusion criteria: Adult COVID-19 patients admitted to the ICU in Modarres hospital, Tehran, Iran (age range of 18 to 99 years) with moderate to severe ARDS (based on definition of P/F ratio) requiring auxiliary respiratory devices (either intubation or face mask). EXCLUSION CRITERIA: ● Existence of a major underlying pulmonary disease in addition to COVID-19 ● Underlying congenital heart disease ● Patients needing extracorporeal membrane oxygenation (ECMO) ● ARDS primarily due to any other reason rather than COVID-19 ● The primary source of pulmonary involvement was bacterial pneumonia or any other etiology except for COVID-10 induced lung involvement ● Those who refused to continue the study (either the patient or their family) ● any patient had any sign of healing before entering the study leading to discharge from ICU in less than 12 hours INTERVENTION AND COMPARATOR: In the intervention group, the dose of the drug is a vial containing 4 ml, equivalent to 100 mg, which is prescribed for an adult weighing about 70 kg each time, and if the patient's weight is much lower or higher, it will be adjusted accordingly. Surfactant is prescribed inside the trachea in two doses, starting on the day of intubation with a second dose 6 hours later. The control group will receive the same volume of normal saline, based on weight, administered into the trachea with the same time schedule. MAIN OUTCOMES: 30 days mortality; patient mortality during stay in ICU up to 30 days; ICU length of stay up to 30 days; Time under mechanical ventilation up to 30 days. RANDOMISATION: After the participant enters the study, i.e. after the qualification of the patients in the trial is confirmed and their informed written consent is taken, we will use a simple randomisation method using a table of random numbers. In order to hide the random allocation process, a central randomisation approach will be used and the random sequence will be at the disposal of one of the researchers, excluding the principal investigator. BLINDING (MASKING): Participants, healthcare providers and the principal investigator assessing the outcomes will all be blinded to the group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 60 participants will be randomised in a 1:1 allocation ratio (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: IRCT registration number: IRCT20091201002804N12 Registration date: 1st June 2020, 1399/03/12 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran.

The Coronavirus Disease 2019 (COVID-19) pandemic has killed many people worldwide since December 2019, and Iran has been among the most affected countries. In this retrospective study, we aimed to determine the prognostic factors associated with mortality in COVID-19 patients by analyzing 396 survived and 63 non-survived patients in Shahid Modarres Hospital, Tehran, Iran, from January 30th until April 5th, 2020. As the results, the BMI > 35 (p = 0.0003), lung cancer (p = 0.007), chronic kidney disease (p = 0.002), Immunocompromised condition (p = 0.003), and diabetes (p = 0.018) were more frequently observed in the expired group. The history of statins use was more common in the discharged group (p = 0.002), while there was no significant difference in the drug history of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, aspirin, and/or steroids, and in the past-year influenza vaccination. Multivariable regression demonstrated rising odds of in-hospital death related with age (odds ratio (OR) = 1.055, p = 0.002), levels of C-reactive protein (CRP) (OR = 2.915, p < 0.001), creatinine (OR = 1.740, p = 0.023), lymphocyte count (OR = 0.999, p = 0.008), and magnesium level (OR = 0.032, p < 0.001) on admission. In conclusion, the patients with older age and higher BMI with lymphopenia, hypomagnesemia, elevated CRP and/or raised creatinine on admission are at higher risk of mortality due to the COVID-19 infection, which requires the physicians to use timely and strong therapeutic measures for such patients.