Predicting the COVID-19 mortality among Iranian patients using tree-based models: A cross-sectional study.

Background and Aims: To explore the use of different machine learning models in prediction of COVID-19 mortality in hospitalized patients. Materials and Methods: A total of 44,112 patients from six academic hospitals who were admitted for COVID-19 between March 2020 and August 2021 were included in this study. Variables were obtained from their electronic medical records. Random forest-recursive feature elimination was used to select key features. Decision tree, random forest, LightGBM, and XGBoost model were developed. Sensitivity, specificity, accuracy, F-1 score, and receiver operating characteristic (ROC)-AUC were used to compare the prediction performance of different models. Results: Random forest-recursive feature elimination selected following features to include in the prediction model: Age, sex, hypertension, malignancy, pneumonia, cardiac problem, cough, dyspnea, and respiratory system disease. XGBoost and LightGBM showed the best performance with an ROC-AUC of 0.83 [0.822-0.842] and 0.83 [0.816-0.837] and sensitivity of 0.77. Conclusion: XGBoost, LightGBM, and random forest have a relatively high predictive performance in prediction of mortality in COVID-19 patients and can be applied in hospital settings, however, future research are needed to externally confirm the validation of these models.

TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients' peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.

A systematic review and meta-analysis of the epidemiological characteristics of COVID-19 in children.

BACKGROUND: Several individual studies from specific countries have reported rising numbers of pediatric COVID-19 cases with inconsistent reports on the clinical symptoms including respiratory and gastrointestinal symptoms as well as diverse reports on the mean age and household exposure in children. The epidemiological characteristics of COVID-19 in children are not fully understood, hence, comprehensive meta-analyses are needed to provide a better understanding of these characteristics. METHODS: This review was conducted in Medline, Scopus, Cochrane library, Embase, Web of Science, and published reports on COVID-19 in children. Data were extracted by two independent researchers and a third researcher resolved disputes. STATA software and the random-effect model were used in the synthesis of our data. For each model, the heterogeneity between studies was estimated using the Q Cochrane test. Heterogeneity and publication bias were calculated using the I2 statistic and Egger's/Begg's tests. RESULTS: The qualitative systematic review was performed on 32 articles. Furthermore, the meta-analysis estimated an overall rate of involvement at 12% (95% CI: 9-15%) among children, with an I2 of 98.36%. The proportion of household exposure was calculated to be 50.99% (95% CI: 20.80%-80.80%) and the proportion of admitted cases was calculated to be 45% (95% CI: 24%-67%). Additionally, the prevalence of cough, fatigue, fever and dyspnea was calculated to be 25% (95% CI: 0.16-0.36), 9% (95% CI: 0.03-0.18), 33% (95% CI: 0.21-0.47) and 9% (95% CI: 0.04-0.15), respectively. It is estimated that 4% (95% CI: 1-8%) of cases required intensive care unit admission. CONCLUSIONS: The pediatric clinical picture of COVID-19 is not simply a classic respiratory infection, but unusual presentations have been reported. Given the high incidence of household transmission and atypical clinical presentation in children, we strongly recommend their inclusion in research and population-based preventive measures like vaccination as well as clinical trials to ensure efficacy, safety, and tolerability in this age group.

The association of APOE genotype with COVID-19 disease severity.

COVID-19 has caused the recent pandemic of respiratory infection, which threatened global health. The severity of the symptoms varies among affected individuals, from asymptotic or mild signs to severe or critical illness. Genetic predisposition explains the variation in disease severity among patients who suffer from severe symptoms without any known background risk factors. The present study was performed to show the association between APOE genotype and the severity of COVID-19 disease. The APOE genotype of 201 COVID-19 patients (101 patients with asymptomatic to mild form of the disease as the control group and 100 patients with severe to critical illness without any known background risk factors as the case group) were detected via multiplex tetra-primer ARMS-PCR method. Results showed that the e4 allele increased the risk of the COVID-19 infection severity more than five times and the e4/e4 genotype showed a 17-fold increase in the risk of severe disease. In conclusion, since our study design was based on the exclusion of patients with underlying diseases predisposing to severe form of COVID-19 and diseases related to the APOE gene in the study population, our results showed that the e4 genotype is independently associated with the severity of COVID-19 disease. However, further studies are needed to confirm these findings in other nations and to demonstrate the mechanisms behind the role of these alleles in disease severity.

Risk Factors of COVID-19 Associated Mucormycosis (CAM) in Iranian Patients: A Single-Center Retrospective Study.

BACKGROUND: COVID-19 associated mucormycosis (CAM) has been known as one of the most severe post-COVID morbidities. OBJECTIVES: To describe CAM cases, identify possible risk factors, and report outcomes of patients. METHODS: This retrospective study was performed in Amir-Alam Hospital, Tehran, Iran between February 2020 and September 2021. Patients with mucormycosis who had an active or previous diagnosis of COVID-19 have been included. RESULTS: Of 94 patients with mucormycosis, 52 (33 men and 19 women; mean age: 57.0 ± 11.82 years) were identified with an active or history of COVID-19. Rhino-orbital, rhino maxillary, rhino-orbito cerebral subtypes of mucormycosis were detected in 6 (11.5%), 18(34.6%), and 28(53.8%) patients. As a control group, 130 (69 men and 61 women; mean age: 53.10 ± 14.49 years) random RT-PCR-confirmed COVID-19 patients without mucormycosis have been included. The mean interval between COVID-19 diagnosis and initial mucormycosis symptoms was 16.63 ± 8.4 days (range 0-51). Those in the CAM group had a significantly more severe course of COVID-19 (OR = 3.60, P-value < 0.01). Known history of previous diabetes mellitus (OR = 7.37, P-value < 0.01), smoking (OR = 4.55, P-value < 0.01), and history of receiving high-dose corticosteroid pulse therapy because of more severe COVID-19 (P-value = 0.022) were found as risk factors. New-onset post-COVID hyperglycemia was lower in the CAM group (46.2% vs. 63.8%; OR = 0.485, P-value = 0.028). After treatment of the CAM group, 41(78.8%) of patients recovered from mucormycosis. The mean ages of the expired patients in the CAM group were significantly higher than those who recovered from mucormycosis (66.18 ± 9.56 vs. 54.56 ± 11.22 years; P < 0.01); and COVID-19 disease was more severe (P = 0.046). CONCLUSION: Either active or history of COVID-19 can cause an increase in the risk of mucormycosis development. Some of the most important risk factors are the medical history of diabetes mellitus, smoking, and high-dose corticosteroid therapy. CAM is important possible comorbidity related to COVID-19, which could make the post-COVID conditions more complicated. More research and studies with greater sample sizes among different ethnicities are needed to explore the association between COVID-19 and mucormycosis.

The association of ACE I/D polymorphism with the severity of COVID-19 in Iranian patients: A case-control study

Background Since the beginning of the COVID-19 pandemic, researchers have tried to find the reason behind the variety of the symptoms and disease severity among patients. It seems that genetic background may contribute in severity of this infection. The renin-angiotensin system (RAS) is involved in the pathogenesis of COVID-19. An Insertion/Deletion (I/D) polymorphism in the ACE1 gene may explain the genetic risk for disease severity. Methods We genotyped 251 COVID-19 patients: 151 patients with mild or asymptomatic disease compared with 100 patients with severe to critical illness (without any comorbidities for the disease severity). Results There was a significant association between the ACE1 DD genotype and disease severity (p-value = 1 × 10−2;OR = 2.004, 95%CI = 1.147–3.499) and our results showed that it was inherited under recessive or codominant inheritance patterns. Also, the I allele showed a protective role against the severe form of COVID-19 disease (p-value = 1 × 10−4). Conclusion We concluded that ACE1 DD genotype can predict the risk of severe form of COVID-19 infection in the absence of known comorbidities as disease severity risk factors. Further studies with larger sample sizes in other populations are still needed to clarify the role of ACE I/D polymorphism in SARS-CoV-2 infection severity.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.

Epidemiological pattern of pediatric trauma in COVID-19 outbreak: Data from a tertiary trauma center in Iran.

INTRODUCTION: In Iran, like most other countries, COVID-19 has had a deep impact on children's lives. Our hypothesis was that, a significant change in the number of pediatric injuries has happened in trauma centers. In the current study, we intend to identify the possible epidemiological shift in pediatric fracture patterns, by comparing the data from 'COVID-19 era' and the mean data from the past 2 years. To the best of our knowledge there are only few reports on epidemiology of pediatric fractures during the COVID-19 outbreak. METHODS: Data are reported in two sections. In the descriptive section, epidemiological data regarding pediatric fractures referred to Taleghani tertiary trauma center, including demographics, distribution curves, etiologies and fracture types are presented during the 'COVID era', from 1 March 2020 to 15 April 2020. In the comparative section, the aforementioned data are compared with mean data from the past 2 years, the 'non-COVID era'. RESULTS: Altogether 117 of the 288 trauma children (40.62%) had a fractured bone (145 fractures). Patients were mostly boys, with a mean age of 9.87 years (SD=5.27). The three most common fracture types in children included distal radius, mid-forearm and humeral supracondylar fractures. Compared to non-COVID era, the number of pediatric trauma admissions dropped from 589 to 288. No significant change happened in the mean age, male/female ratio and percentage of motor vehicle accidents. Proportion of proximal humeral, proximal forearm, carpal, and hand fractures declined. The number of open fractures significantly dropped (from 12 to 2). CONCLUSIONS: In Iran, overall trend of pediatric trauma has been decreasing during the outbreak; but the lack of reduction in proportion of accidents may pose an alarm that an effective lock-down has not been imposed. This study has implications as to preparing appropriate resources particular to common "COVID era fractures".

Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.

BACKGROUND: The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19. METHODS: We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events. RESULTS: The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss. CONCLUSION: Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO2 < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.

A Randomized Clinical Trial of the Efficacy and Safety of Interferon ß-1a in Treatment of Severe COVID-19.

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).