Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial.

BACKGROUND: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV). METHODS: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions. RESULTS: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths. CONCLUSIONS: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.

Investigating the factors affecting the survival rate in patients with COVID-19: A retrospective cohort study.

Background: As hospitalized patients with COVID-19, especially those who are admitted to ICU or die afterwards, generally have comorbidities, the aim of this study was to determine the factors affecting the survival rate of COVID-19 patients in Iran using a retrospective cohort. Methods: This retrospective cohort study was conducted on patients with COVID-19 who referred to medical centers under the supervision of Iran University of Medical Sciences, Tehran, Iran, from February 22 to March 25, 2020. The final date of follow-up was April 19, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Clinical laboratory, radiological, treatment, and demographic data were collected and analyzed. The associations among gender, immune disease, diabetes, liver disease, cardiovascular disease, kidney disease, chronic pulmonary disease, cancer, chronic nervous disease, type of treatment, and risk of death were analyzed. The Kaplan-Meier and Log-rank tests were used to estimate survival rate and compare survival rates, respectively. Results: The total number of deaths or desired event in the study was 329 (10.3%).The risk of death in the age groups of 50-60 years, 60-70 years, and >70 years compared to the 30-40 age group was 2.17 (95% CI: 1.03, 4.55; p: 0.040); 3.72 (95 % CI: 1.80, 7.68; p: 0.001) and 5.09 (95 % CI: 2.49, 10.40; p: 0.001), respectively. The results showed men had 11.5% more risk of deaths than women (HR: 1.11; 95 % CI: 0.89, 1.39; p: 0.341). Kidney disease increased the risk of death by 52.3% in these patients, which was not statistically significant (HR: 1.78; 95 % CI: 1.04, 3.04; p: 0.035). Also, chronic pulmonary diseases and diabetes increased the risk of death in COVID-19 patients by 89.5% and 41.3% compared to COVID-19 patients without chronic pulmonary diseases and diabetes [(HR: 1.89; 95 % CI: 1.17, 3.04; p: 0.008), (HR: 1.41; 95 % CI: 1.01, 1.96; p: 0.038)]. Conclusion: Based on the results of this study, more attention and care should be paid to COVID-19 patients with underlying diseases, such as chronic obstructive pulmonary disease, diabetes, and kidney disease to reduce the number of deaths.

Safety and efficacy of RCP recombinant spike protein covid-19 vaccine compared to Sinopharm BBIBP: A phase III, non-inferiority trial.

Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the non-randomized arm). We observed 604 primary outcome events during 4 months of active follow-up including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71-1.16) and 0.62 (0.49-0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67-1.22) remained below the margin of non-inferiority in the randomized arm after observing the early stopping rules using O'Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP.

Trend of mortality rate due to traffic accidents in Iran from 2006 to 2020: A cross-sectional study.

Background: Traffic accidents are a common global cause of mortality and physical disability. This study aimed to investigate traffic accident-related mortality trends across provinces in Iran. Methods: In this study, information on all deaths caused by traffic accidents in Iran from 2006 to 2020 was collected from the Iranian Legal Medicine Organization, which collects annual data from all 31 Iranian provinces. The national and provincial demographics were assessed, and the trends in mortality rates were assessed over a 15-year span using joinpoint regression based on the log-linear model, with results expressed in terms of annual percentage change (APC). The analysis for the trend was performed using the Joinpoint Regression Program 4.9.0.1. Results: During the study period, 291,774 traffic accident-related deaths occurred in Iran, of which 78.6% were men and 21.4% were women. The mean age of the deceased was 37.75 ± 20.89 years. The mortality rate has dropped from 39/100,000 in 2006 to 18.3/100,000 in 2020. In total, the national mortality rate APC for 2006-2015 was -6.3% (P < 0.05) and for 2015-2020 was - 1.70% (P > 0.05). Conclusions: Despite the overall decreasing national trend in Iran's traffic accident-related mortality over the study period, the provincial variability was noted. Therefore, it seems necessary to design and conduct epidemiological studies in different areas and provinces, for a better and more accurate understanding of the factors affecting the occurrence of traffic accident-related deaths, resulting in more focused and measurable interventions.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

Investigation of Death Rate Due to Type 2 Traffic Accidents and Non-Traffic Accidents in Iran during 2013-2018.

Background: In the classification of road accidents, type 2 traffic accidents and non-traffic accidents are not considered and in Iran so far no special study has been done in the field of type 2 traffic accidents and non-traffic accidents, so we aimed to investigate the incidence of type 2 traffic accidents and non-traffic accidents in Iran. Methods: This cross-sectional was conducted on all individuals referred to Forensic Medicine Organization (FMO) from all over Iran who suffered from non-traffic accidents and type 2 traffic accidents during 2013-2018. Demographic information, accident information and other information including the location of the impact, the final cause of death and the date of the accident were examined. The information received from the FMO was first checked and then analyzed using Stata 11 statistical software. Results: During the 6-year study period, 10882 people lost their lives in type 2 traffic accidents (4779 people) and non-traffic accidents (5287 people). In terms of age, the highest incidence of type 2 traffic accidents and non-traffic accidents was observed in the age group over 65 years. The incidence of type 2 traffic accidents has not been increasing, while the trend of non-traffic accidents has been increasing. Conclusion: With respect to the high rate of deaths due to traffic accidents, including type 2 traffic accidents and non-traffic accidents, it is necessary for the national media and relevant agencies to educate the people about first aid and also inform about free relief services, timely presence is important.

Risk of gestational diabetes mellitus by pre-pregnancy body mass index: A systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) is serious health challenges. This study aimed at determining the risk of GDM among pregnant women by pre-pregnancy BMI. Five electronic databases including Medline (PubMed), Scopus, Embase, Web of Science and Google Scholar were searched for literature published form 2015 to January 1, 2021. The pooled estimate risk of GDM among pregnant women was 16.8% (95% CI: 15.3-18.4). The risk of GDM in underweight/normal group and overweight/obese group were 10.7% (95% CI: 9.1-12.4) and 23% (95% CI: 20.2-25.9), respectively. The risk of GDM is high among overweight/obese pregnant women.

Utilization of dental care in Iranian pregnant women: Findings from a population-based study.

BACKGROUND: Although dental care attendance during pregnancy has been recommended by guidelines and institutions, the demand for dental services is still low among pregnant women. The aim of this study was to examine the prevalence of not receipt dental care and also determinants of that during pregnancy. MATERIALS AND METHODS: This population-based study was conducted on 4071 mothers in 10 provinces of Iran, during 2014-2015. We calculated the prevalence of not receipt of dental care, and reasons for nonreceipt of care. We used logistic regression to estimate odds of nonreceipt of care by demographics variables. In the analyses, the level of statistical significance was set at P < 0.05. RESULTS: Overall, 54.70% of women had no dental visit during pregnancy. In mothers who had a history of stillbirth, neonatal death and live birth, the prevalence of not receipt dental care during pregnancy were 54.56%, 48.92%, and 58.76%, respectively. The logistic regression analyses showed that parity second-to-fourth birth than first birth (odds ratio [OR] 1.37 confidence interval [CI] 95% 1.17-1.59, residence in rural (OR 1.68 CI 95% 1.45-1.95), and not intended pregnancy (OR 1.32 CI 95% 1.03-1.68) associated with not received dental care during pregnancy. CONCLUSION: Most pregnant women in this study received insufficient dental care. The need for dental care during pregnancy must be promoted widely among women of reproductive age, and family barriers to dental care should be addressed.

Diabetes, Hypertension, and Incidence of Chronic Kidney Disease: Is There any Multiplicative or Additive Interaction?

BACKGROUND: The burden of chronic kidney disease (CKD) is on the rise worldwide; diabetes and hypertension are mentioned as the main contributors. OBJECTIVES: The current study aimed to investigate the multiplicative and additive interaction of diabetes and hypertension in the incidence of CKD. METHODS: In this population-based cohort study, 7342 subjects aged 20 years or above (46.8% male) were divided into four groups: no diabetes and hypertension; diabetes and no hypertension; hypertension and no diabetes; and both diabetes and hypertension. The multivariable Cox regression was used to determine the effect of diabetes, hypertension, and their multiplicative interaction on CKD. The following indices were used to determine the additive interaction of diabetes and hypertension: the relative excess risk of interaction, the attributable proportion due to interaction, and the synergism index. RESULTS: Diabetes and hypertension had no significant multiplicative interaction in men (hazard ratio of 0.93, P value: 0.764) and women (hazard ratio of 0.79, P value: 0.198); furthermore, no additive interaction was found in men (relative excess risk due to interaction of 0.79, P value: 0.199; attributable proportion due to interaction of 0.22, P value: 0.130; synergy index of 1.44, P value: 0.183) and women (relative excess risk due to interaction of -0.26, P value: 0.233, attributable proportion due to interaction of -0.21, P value: 0.266; synergy index of 0.48, P value: 0.254). CONCLUSIONS: This study demonstrated no synergic effect between diabetes and hypertension on the incidence of CKD.

Cigarette Smoking and Health-related Quality of Life in the General Population of Iran: Independent Associations According to Gender.

BACKGROUND: Associations between smoking and health-related quality of life (HRQoL) in the general population remain unclear. The aim of the study was to quantify the independent associations between smoking and HRQoL. METHODS: A cross-sectional population-based study was conducted on a total sample of 2197 participants obtained by multistage sampling to investigate the associations between smoking and HRQoL in the general population of southeast and southwest of Iran, aged 18-100 years in 2012-2013. Data were collected using a self-administrated of the 36-Item Short Form Survey (SF-36) questionnaire. Linear regression analyses were used to evaluate the associations between HRQoL and smoking while adjusting for various socioeconomic variables. In this study, P < 0.05 was considered a significant difference. RESULTS: Out of the total of 2197 participants, current smokers and never smokers accounted for 13% and 87%, respectively. The mean HRQoL indices were for the current smokers 66.66 ± 17.86, and never smokers 71.35 ± 18.47 (P < 0.001). Independent associations between smoking and HRQoL were found, including negative associations (P < 0.001). The multivariate associations between smoking status and HRQoL, male smokers had a lower physical functioning, mental health, and total SF-36 score. CONCLUSIONS: Smoking was independently related to HRQoL, with large differences according to the gender. This study showed that there is a significant difference in the quality of life related to health in male smokers compared to male nonsmokers.

Cadmium in Groundwater Consumed in the Rural Areas of Gonabad and Bajestan, Iran: Occurrence and Health Risk Assessment.

Evidences show that high levels of cadmium intake may be contributing to a wide range of deleterious health effects. This study was performed to estimate the concentration of cadmium and the health risk to human by cadmium through the ingestion of groundwater in 39 rural areas of Gonabad and Bajestan, eastern Iran. The mean cadmium concentrations in groundwater in the studied rural areas of Gonabad and Bajestan ranged from 0.087 to 14.32 µg/L and from 0.417 to 18.36 µg/L, respectively. Health risk quotient for cadmium contamination for 16 and 38% of children and infants in rural areas of Gonabad and Bajestan, respectively, was more than 1 which causes non-carcinogenic risk to the local population. The carcinogenic risk of cadmium in drinking water for adults, children, and infants in 16, 33, and 33% of studied rural areas of Gonabad and Bajestan, respectively, was higher than the safe limit of 1.0 × 10-4. For rural areas of Bajestan, the cancer risk in 42, 52, and 52% of adults, children, and infants was above the safe limit. It was strongly suggested that the accessible procedures of treatment should be taken for a portion of contaminated rural areas before the distribution of the groundwater for the local population.

Spatial analysis of mortality rate of pedestrian accidents in Iran during 2012-2013.

Objectives: Considering the high mortality rate of pedestrians in traffic accidents in Iran, the present study aimed to determine the high-risk and low-risk areas of accidents resulting in pedestrian deaths and the spatial analysis of their mortality rates. Methods: This cross-sectional study included 4,371 deceased pedestrians reported by the Legal Medicine Organization in Iran from March 2012 to March 2013. For spatial analysis, the collected data were entered into ArcGIS software version 10.2 and a spatial map of the mortality rate was drawn according to the distribution of data in the provinces. Using this software, high-risk and low-risk areas were identified by calculating the spatial autocorrelation of the data. The Moran's index of road accident patterns was surveyed and high-risk and low-risk points were identified using the local Getis index. Results: The age-standardized incidence rate was 6.8 per 100,000. After analyzing the data using ArcGIS software, the local Moran's index showed a cluster pattern with a high mortality rate in 3 provinces of Mazandaran, Gilan, and Qazvin. In identifying high-risk and low-risk points, the local Getis index showed 3 hot spots with a confidence interval of 99% in Qom, Qazvin, and Mazandaran and 5 hot spots with a 95% confidence interval in Markazi, Tehran, Zanjan, Gilan, and Golestan provinces. Conclusions: According to the cluster pattern of accidents in the 3 provinces and the presence of hot spots in 9 provinces, it is necessary to identify factors that increase the risk of death in the study provinces in order to reduce the mortality rate among pedestrians due to traffic accidents. Therefore, to reduce the pedestrian mortality rate, especially in high-risk provinces, some studies need to be conducted to determine the risk factors in pedestrian mortality.