Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals.

BACKGROUND: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. RESULTS: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. CONCLUSIONS: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses.

Prevalence of acquired and transmitted HIV drug resistance in Iran: a systematic review and meta-analysis.

BACKGROUND: There is no systematic review on the prevalence of HIV drug resistance (HIVDR) in Iran. We aimed to estimate the prevalence of HIVDR among people living with HIV (PLHIV) in Iran. We assessed HIVDR prevalence in antiretroviral therapy (ART) naïve PLHIV (i.e., those without a history of ART) and PLHIV receiving ART. METHOD: We systematically searched Scopus, PubMed, Web of Science, Embase, Iranian databases (Iranian Medical Research Information System, Magiran, and Scientific Information Database), the references of studies, and Google Scholar until March 2023. A random-effects model was used to calculate a point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in PLHIV. RESULTS: Among 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in PLHIV receiving ART was 34% (95% CI: 19, 50) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27% (95% CI: 15, 41) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9% (95% CI: 3, 18) for protease inhibitors (PIs). The pooled prevalence of acquired HIVDR in treatment failure PLHIV was 50% (95% CI: 31, 69) for NRTIs, 49% (95% CI: 29, 69) for NNRTIs, 11% (95% CI: 2, 24) for PIs, and 1% (95% CI: 0, 4) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in ART-naïve people was 3% (95% CI; 1, 6) for NRTIs, 5% (95% CI: 2, 9) for NNRTIs, and 0 for PIs and INIs. CONCLUSION: The prevalence of HIVDR was relatively high in both ART-naïve PLHIV and those receiving ART. Without universal pretreatment HIVDR testing and more frequent routine HIV viral load testing among PLHIV who are on ART, the HIVDR prevalence might increase in PLHIV in Iran.

Epidemiology and spatial distribution of people diagnosed with HIV between 1997 and 2020 in Kerman, Iran.

OBJECTIVE: This study described the epidemiology and geographical distribution of people diagnosed with HIV in Kerman, Iran, between 1997 and 2020. METHODS: We used case-based HIV surveillance data of all people diagnosed with HIV in Kerman between 1997 and 2020. We compared the age, gender, modes of transmission and spatial distribution of newly diagnosed HIV-infected people in three time periods (1997-2004, 2005-2012 and 2013-2020). The χ2 test for trend, one-sample t-test and Kruskal-Wallis H test were used to compare the differences between the three time periods. We also used ArcGIS to map both HIV services and people living with HIV (PLWH) in 2020. The nearest neighbour index and kernel density were used to identify the spatial distribution of PLWH. RESULTS: A total of 459 (27.5% women) people were diagnosed with HIV during 1997-2020. The proportion of women (9.3% in 1997-2004 and 48.3% in 2013-2020, p<0.001), HIV infection through sexual contacts (11.6% in 1997-2004 and 50.3% in 2013-2020, p<0.001), HIV infection under the age of 5 years (0.8% in 1997-2004 and 5.4% in 2013-2020, p=0.01) and mean age at diagnosis among men (34.9 in 1997-2004 and 39.8 years in 2013-2020, p=0.004) significantly increased over time. 36.2% of diagnosed cases had CD4 counts under 200 x 10ˆ6/L between 2013 and 2020, with no significant improvement over time. Most newly diagnosed cases of HIV were from the eastern parts of the city. The clusters of PLWH in 2020 matched with the locations of HIV services. CONCLUSION: We observed important changes in HIV epidemiology regarding gender, modes of transmission, number of paediatric cases and density maps over time in Kerman. These changes should be considered for precise targeting of HIV prevention and treatment programmes.

Epidemiological surveillance of respiratory viral infections in SARS-CoV-2-negative samples during COVID-19 pandemic in Iran.

BACKGROUND: To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran. METHODS: In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records. RESULTS: In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years. CONCLUSION: Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts.

Comparison of a Multiplex Real-Time PCR Technique with Oxford Nanopore Technologies Next-Generation Sequencing for Identification of SARS-CoV-2 Variants of Concern.

INTRODUCTION: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in comparison to the next-generation sequencing (NGS) as a gold standard assay, particularly in developing countries. This study was designed to evaluate the performance of a commercial multiplex real-time PCR technique (GA SARS-CoV-2 OneStep RT-PCR Kit, Iran) for identification of SARS-CoV-2 variants of concern (VOCs) compared to the Oxford Nanopore NGS assay. METHODS: A total of 238 SARS-CoV-2-positive respiratory samples from different waves of COVID-19 in Iran were randomly selected in this study. To determine the SARS-CoV-2 VOC, the samples were analyzed via the commercial triple target assay, GA SARS-CoV-2 OneStep RT-PCR Kit, and NGS as well. RESULTS: The results revealed good concordance between GA SARS-CoV-2 OneStep RT-PCR Kit and NGS for identification of SARS-CoV-2 VOCs. GA SARS-CoV-2 OneStep RT-PCR Kit identified Wuhan, Alpha, and Delta variants with 100% relative sensitivity and specificity. Regarding Omicron subvariants of BA.1, BA.2, and BA.4/5, the relative sensitivity of 100%, 100%, and 81.5% and the relative specificity of 95.3%, 93.5%, and 100% were observed. CONCLUSION: Overall, GA SARS-CoV-2 OneStep RT-PCR Kit can be used as a rapid and cost-effective alternative to NGS for identification of SARS-CoV-2 VOCs.

Genetic characterization of P[8] rotavirus strains circulated in Iran between 2009 and 2017.

Group A rotavirus (RVA) is the most common cause of acute gastroenteritis worldwide, which is responsible for causing an estimated 120 000 deaths in children under 5 years of age, which mostly occur in the lower-income countries of Asia and Africa. The G1P[8] is a common genotype of RVA that has spread throughout the world, including Iran and this genotype is present in two commonly used RVA vaccines, RotarixTM and RotaTeqTM . In this study, we investigated the genetic diversity, viral evolution, and differences between antigenic epitopes of Iran's P[8] strains and two licensed vaccines. The phylogenetic and evolutionary analysis was carried out, using MEGA version 6.0 and BEAST, respectively. Antigenic epitopes of VP8* were compared to determine the differences between strains from Iran and RotarixTM and RotaTeqTM . The P[8]-lineages III and IV were found as the predominant P genotype that circulated in Iran. The TMRCA of P[8]-lineages III and IV was estimated in 1987 and 2009, respectively. The P[8]-lineage III strains showed 12 amino acid changes compared to RotarixTM and 10 amino acid changes compared to RotaTeqTM . The P[8]-lineage IV strains showed 10 amino acid variations for both RotarixTM and RotaTeqTM strains. The results revealed that the P[8] strains circulating in Iran differ from RotarixTM and RotaTeqTM strains. To monitor the long-term effects of vaccines on the emergence of P[8] strains with different lineages, routine and successful monitoring of these strains will be crucial.

Reconstruction of molecular evolution of human influenza A H1N1/2009 virus in Iran and neighboring countries.

In this study, the time and path of transmission of H1N1 serotype influenza A viruses in Iran and neighboring countries have been investigated by using Bayesian phylogeography analysis on the sequences extracted from the gene bank. We obtained all hemagglutinin (HA) and neuraminidase (NA) nucleotide sequences of influenza H1N1 available up to December 25, 2020, from Iran and its neighboring countries (i.e., Pakistan, Afghanistan, Turkmenistan, Armenia, Azerbaijan, Turkey, and Iraq). We also performed a Bayesian Markov chain Monte Carlo method to infer the evolutionary dynamic and the most recent common ancestor for the HA and NA sequences. Based on the extracted sequences, the age of emergence of H1N1 influenza virus serotype was older in Iran compared to neighboring countries, and with some degree of uncertainty, it seems Tehran had a key role and epicenter of transmission to other cities within Iran. The mean time of the most recent common ancestor of H1N1 viruses was 1989 (95% HPD: 1980-1994) for HA and NA as well. Along with ordinary measures like resource management, diagnostic approaches, and preparedness to fight against viruses that were in place, continuous monitoring, and screening of H1N1 serotype influenza virus in the country, especially by implementation of feasible, effective, and innovative measures at borderline should be initiated and identified gaps and shortage that should be a priority for virus control. It is also important for countries to have a regional monitoring program in addition to internal monitoring programs, as well as to start a virus molecular care program.

Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of Candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections.

Vulvovaginal candidiasis (VVC) is a prevalent infection of the genitourinary tract affecting millions of women worldwide. In the present study, the importance of virulence factors, ERG11 gene mutations, ERG11 gene expression, and plasma membrane ergosterol content for fluconazole resistance in Candida species was investigated in 200 women suspected of vulvovaginitis. Isolated Candida species were identified using the ITS-restriction fragment length polymorphism (ITS-RFLP) technique. Antifungal susceptibility testing was performed according to the CLSI document. ERG11 gene expression was analyzed using real-time PCR. ERG11 gene mutation analysis was performed using sequencing methods, and the ergosterol content of the cell membrane was determined in fluconazole-resistant isolates. Furthermore, the production of phospholipase and proteinase enzymes was evaluated in recurrent and non-recurrent infections. VVC was diagnosed in 101 (50.5%) of the 200 clinical cases, of which 21 (20.8%) were confirmed as RVVC. Candida albicans was the most prevalent species, followed by C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. Ketoconazole and fluconazole were the most effective drugs against C. albicans among five tested antifungals with MIC ranges between 0.06 and 16 µg/mL and 0.25-64 µg/mL. Substitutions of A114S, Y257H, T123I and A114V were detected in fluconazole-resistant C. albicans. The ergosterol content of the fungal cell membrane and the mean levels of ERG11 gene expression transcript were higher in fluconazole-resistant C. albicans isolates obtained from RVVC than in those obtained from VVC cases. Phospholipase and proteinase were produced in different amounts in all Candida species isolated from VVC and RVVC cases. In this review, our results demonstrated that several molecular mechanisms, including ERG11 gene expression, changes in the cell membrane ergosterol content, and mutations in ERG11 gene alone or simultaneously involved in fluconazole resistance of C. albicans species and the recurrence of VVC.

Comparing the expression levels of tripartite motif containing 28 in mild and severe COVID-19 infection.

BACKGROUND: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients. RESULTS: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection. CONCLUSION: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins.

Barriers and facilitators of access to HIV prevention, care, and treatment services among people living with HIV in Kerman, Iran: a qualitative study.

BACKGROUND: Low access to HIV prevention, care, and treatment services among people living with HIV (PLWH) is a barrier to the control of the epidemic worldwide. The present study aimed to assess the barriers and facilitators to HIV services among PLWH in Kerman, Iran. METHODS: In this qualitative study, a convenience sample of 25 PLWH who had received HIV prevention, treatment, or care services, and six PLWH who had not yet received services were recruited between August-October 2020. Data were collected using a semi-structured, face-to-face interview. Data were examined by inductive content analysis using MAXQDA 10 software. RESULTS: Nine categories of facilitators and 11 categories of barriers to HIV services were identified. Facilitating factors included: maintaining health status, feeling scared, trust in the health system, how they were treated by service providers, provision of suitable hours by the service provider center, changing attitudes towards HIV in society, acceptance of the disease by the patient's family, hope for the future and feeling the need for consulting services. Barriers included financial problems, side effects and belief in efficacy, distance and transportation problems, fear of being recognized, stigma towards PLWH, organization of services, improper treatment by service providers, unsuitable hours by the service provider center, lack of trust in the health system, lack of family support, and inadequate or low-quality service. CONCLUSION: Many facilitators and barriers to HIV prevention, treatment, and care are amenable to change and better management by healthcare and service providers. Addressing these factors is likely to increase the willingness to use services by those who have never previously accessed them.

Dynamic Changes of Mitochondrial DNA Copy Number in Gastrointestinal Tract Cancers: A Systematic Review and Meta-Analysis.

We have performed a systematic review and meta-analysis for evaluation of mitochondrial DNA copy number (mtDNA-CN) alterations in peripheral blood leukocytes (PBL), and tumor tissues of gastrointestinal tract (GIT) cancers. Analysis of the PBL demonstrated a significant decrease [OR: 0.6 (0.5, 0.8)] and increase [OR: 1.4 (1.1, 1.9)] prior to and following GIT cancer development, respectively. This trend was more evident in CRC, and GC subgroups. Analysis of tissue yielded high levels of heterogeneity. However, the mean difference for the CRC subgroup was statistically significant [1.5 (1.0, 2.2)]. Our analysis suggests mtDNA-CN deserves further investigations as a GIT-cancer screening tool.

Association of the host genetic factors, hypercholesterolemia and diabetes with mild influenza in an Iranian population.

BACKGROUND: Variation in host genetic factors may result in variation in the host immune response to the infection. Some chronic diseases may also affect individuals' susceptibility to infectious diseases. The aim of this study was to evaluate the association of the host genetic factors mostly involved in inflammation, as well as hypercholesterolemia and diabetes with mild flu in an Iranian population. METHODS: In this cross-sectional study, nasopharyngeal swab samples were collected from 93 patients referred to primary care centers of Markazi, Semnan, and Zanjan provinces (central Iran) due to flu-like symptoms between March 2015 and December 2018. Of these, PCR test identified 49 influenza A/H1N1 and 44 flu-negative individuals. Twelve single-nucleotide polymorphisms (SNPs) in RPAIN, FCGR2A, MBL-2, CD55, C1QBP, IL-10, TNF-α and an unknown gene were genotyped using iPLEX GOLD SNP genotyping analysis. Hypercholesterolemia and diabetes status was determined based on the physician diagnosis. Association of the host genetic variants, hypercholesterolemia and diabetes with mild A/H1N1 flu was assessed with univariable and multivariable logistic regression analysis as implemented in Stata software (v.14). Statistical tests were considered as significant at 0.05 levels. RESULTS: Frequency of diabetes and hypercholesterolemia, as well as participants mean age was significantly higher in the flu-negative rather than the flu-positive group. Of 12 SNPs, nine did not show any significant association with mild flu in our study (rs1801274, rs1800451, rs2564978, rs361525, rs1800450, rs1800871, rs1800872, rs1800896, rs1800629). Possessing G vs. A allele in two SNPs (rs3786054 and rs8070740) was associated with a threefold increase in the chance of mild flu when compared to flu-negative patients (95% CI: 1.1, 22.0). Possessing C allele (vs. A) in the rs9856661 locus also increased the chance of mild flu up to 2 folds (95% CI: 1.0, 10.0). CONCLUSION: The results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1QBP and RPAIN genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient's age, BMI, diabetes, and hypercholesterolemia. Complementary functional genomic studies would shed more light on the underlying mechanism of human immunity associated with these genetic markers. The identified genetic factors may have the same role in susceptibility to similar respiratory infections with RNA viruses, like SARS, MERS and COVID-19. Future genetic association studies targeting these RNA viruses, especially COVID-19 is recommended. Studies on other ethnic groups would also shed light on possible ethnic variations in genetic susceptibility to respiratory RNA viruses. Trial registry IR.PII.REC.1399.063.

Prevention of mother-to-child HIV transmission program in Iran.

BACKGROUND: The reproductive health and Prevention of Mother-to-Child Transmission (PMTCT) of HIV programs in Iran were integrated as a pilot project in September 2014. This study aims to provide a comprehensive evaluation and analysis of the PMTCT of HIV program in Iran. METHODS: The pilot phase of PMTCT of HIV was launched in early September 2014 in selected centers including 170 health centers and 40 hospitals affiliated to medical universities of 16 provinces of Iran. In each medical university, a researcher-made checklist was administered to all newly-diagnosed HIV-positive pregnant women by an AIDS expert. Data was analyzed using SPSS 19. RESULTS: Overall, 69.4% of eligible pregnant women were enrolled in the pilot phase. From 134 reactive cases, 76 (56.7%) were confirmed as HIV positive. ARV consumption was irregular in 10 (13.2%) of HIV positive pregnant women. Also, 82.5% had CD4 count more than 350 after treatment, with an average of 55.5% increase in the number of CD4 in comparison to the baseline, and 84.8% had viral load suppression (< 200 copies/ml). Counseling and testing was done for the husbands of 75% of the women that resulted in the identification of 15 (39.5%) new HIV cases among husbands. Among the tested individuals, 23 (60.5%) males already knew their HIV status and were registered as HIV patients. HIV was diagnosed in one (1.5%) newborn. CONCLUSION: Implementation of rapid HIV testing and PMTCT in Iran is one of the strengths of the national HIV control program. To eliminate MTCT, it is necessary to understand and overcome the barriers and challenges to the program in the pilot phase.

Severity and mortality of COVID-19 infection in HIV-infected individuals: Preliminary findings from Iran.

Background: Higher mortality due to coronavirus disease 2019 (COVID-19) is reported among some immunocompromised patients; however, the relation between immunosuppression due to HIV infection and severity of COVID-19 infection remains unclear. We aimed to investigate the severity and mortality of COVID-19 infection in HIV-infected patients. Methods: This was a retrospective cohort study on all COVID-19 suspected and confirmed cases hospitlized in Iran between Febuary 19 (epidemic onset date) and April 8, 2020, whose data were recorded in the national database for Medical Care Monitoring Center. Hospitalized patients were followed from admittion to death/discharge. Patients' HIV status was recorded based on their self report. Logistic and Cox regression models were used to evaluate the association between HIV infection and the severity (according to the Glascow-Coma Scale situation, need for intubation and hypoxemia) and mortality of COVID-19 infection, respectively. Analyses were performed separately for COVID-19 suspected and confirmed cases. Results: Out of 122 206 severe acute respiratory infection (SARI) cases, 90 were HIV-positive (0.07%), with a similar mean age (Pt-test= 0.750) and distrubtion of gender (PChi-square= 0.887) and nationality (PChi-square= 0.202) as HIV-negative patients. A comparable proportion of HIV-positive and HIV-negative cases were tested for COVID-19 (p= 0.170); however, the frequency of positive results was lower among HIV-positives (p= 0.038). The frequency of COVID-19 and HIV coinfection was lower than expected among confirmed cases (adjusted OR= 0.54; 95% CI: 0.29-1.02) and suspected cases (adjusted OR= 0.68; 95% CI: 0.45- 1.02), which means that the frequency of COVID-19 infection was lower among HIV-positive cases. HIV infection decreased the risk of death among confirmed (adjusted HR= 0.33; 95% CI: 0.05-2.32), suspected cases (adjusted HR= 0.81; 95% CI: 0.33-1.94), and among SARI cases (adjusted HR= 0.73; 95% CI: 0.35-1.54). Conclusion: Our findings support the concept that HIV infection was not a risk factor to increase the severity and risk of death among COVID-19 infected patients.

Association of cigarette smoking, obesity, and underlying medical conditions with COVID-19 hospitalization and mortality in Iran: A nationwide retrospective ecological study.

Background: Coronavirus Disease 2019 (COVID-19) has resulted in a considerable number of deaths worldwide. This ecological study aimed to explore the relationship between COVID-19 hospitalization and mortality with smoking, obesity, and underlying conditions in Iran. Methods: Provincial-level COVID-19 data were obtained from the official reports. Two outcomes were assessed: the total number of hospitalizations and deaths. Data on underlying health conditions, cigarette smoking, and obesity were obtained from national surveys. Negative binomial regression was used to report incident rate (IRR) ratios. Results: As of April 22, 2020, a total number of 43 950 lab-confirmed COVID-19 hospitalizations and 5391confirmed COVID-19 deaths were officially reported. Adjusting for underdetection to cover the number of clinically-confirmed COVID-19 cases, a total of 76 962 additional hospitalizations (ie, total lab- and clinically-confirmed hospitalizations = 120 912; 175% increase) and 7558 additional deaths (ie, total lab- and clinically-confirmed deaths = 12 949; 140% increase) were estimated during the same period. Provinces with a higher prevalence of obesity (IRR: 2.75, 95% CI: 1.49, 5.10), cigarette smoking (1.81; 95% CI: 1.01, 3.27), hypertension (1.88; 95% CI: 1.03, 3.44), and diabetes mellitus (1.74; 95% CI: 0.96, 3.16) had a higher likelihood of COVID-19 death rates. Conclusion: Inequality in COVID-19 hospitalization and mortality was observed in provinces whose populations had underlying diseases, in particular, obesity, cigarette smoking, hypertension, and diabetes.

Adherence to Self-isolation measures by older adults during coronavirus disease 2019 (COVID-19) epidemic: A phone survey in Iran.

Background: Older adults are at higher risk for severe illness and death associated with coronavirus disease 2019 (COVID-19). As Iran was affected by COVID-19 pandemic, the elderly population soon were told to self-isolate for a very long time. We aimed to identify the coverage, efficacy, and integrity of self-isolation and its predictors in the Iranian older adults (≥60 years) from February 19 to 19 March 2020. Methods: Quota sampling was performed to recruit respondents from 16 cities that were selected based on their population size (4, 7, and 5 cities for localities with ≤500 000, 500 000-1 000 000, and ≥1 000 000 populations) and geographical direction (West = 4 cities; North, East, South, Center = 3 each). At least 30 respondents per locality were selected. Phone interviews of 558 respondents (out of 560; response rate = 99.6%) were performed by local trained interviewers using a validated interview form. Association between age, sex, and living condition (with family vs alone) was assessed with Pearson Chi Square and logistic regression analyses. Results: Complete self-isolation was reported by 61% of the respondents. In 72%, self-isolation led to 80%-100% contact reduction. Self-isolation was broken by 26% of the respondents. Females had better self-isolation behaviors (OR adjusted: 2.3, 95% CI: 1.5, 3.3) and higher contact reduction rates (p: 0.067). They kept the integrity of self-isolation better (OR adjusted: 1.8; 95% CI: 1.2, 2.7). Those aged older than 80 years were 2.3-folds more likely to completely self-isolate than younger elderly (95% CI adjusted: 1.2, 4.3). Living alone did not significantly predict self-isolation features in the elderly. Conclusion: About one third of the interviewed Iranian older adults did not adhere to important self-isolation measures, with males and younger ages showing lower adherence. With the relaxation of social distancing measures, protection measures of the elderly should be strengthened. Given that prolonged self-isolation adversely affects physical and mental health status of the elderly, it is highly recommended to think of creative and gender-specific methods that best tailor the needs of this population in Iran.

Leishmania tropica isolates from non-healed and healed patients in Iran: A molecular typing and phylogenetic analysis.

The precise identification of the parasite species causing leishmaniasis is essential for selecting proper treatment modality. The present study aims to compare the nucleotide variations of the ITS1, 7SL RNA, and Hsp70 sequences between non-healed and healed anthroponotic cutaneous leishmaniasis (ACL) patients in major foci in Iran. A case-control study was carried out from September 2015 to October 2016 in the cities of Kerman and Bam, in the southeast of Iran. Randomly selected skin-scraping lesions of 40 patients (20 non-healed and 20 healed) were examined and the organisms were grown in a culture medium. Promastigotes were collected by centrifugation and kept for further molecular examinations. The extracted DNA was amplified and sequenced. After global sequence alignment with BioEdit software, maximum likelihood phylogenetic analysis was performed in PhyML for typing of Leishmania isolates. Nucleotide composition of each genetic region was also compared between non-healed and healed patients. Our results showed that all isolates belonged to the Leishmania tropica complex, with their genetic composition in the ITS1 region being different among non-healed and healed patients. 7SL RNA and Hsp70 regions were genetically identical between both groups. Variability in nucleotide patterns observed between both groups in the ITS1 region may serve to encourage future research on the function of these polymorphisms and may improve our understanding of the role of parasite genome properties on patients' response to Leishmania treatment. Our results also do not support future use of 7SL RNA and Hsp70 regions of the parasite for comparative genomic analyses.

Association of IFITM3 rs12252 polymorphisms, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population.

BACKGROUND: IFITM3 has been suggested to be associated with infection in some ethnic groups. Diabetes and hypercholesterolemia are also important clinical conditions that can predispose individuals to infection. The aim of this study was to investigate the association of rs12252 C polymorphism, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population. METHODS: We conducted a case-control study, including 79 mild flu and 125 flu-negative individuals attending primary care centers of three provinces of Iran (i.e, Markazi, Semnan, and Zanjan). Pharyngeal swab specimens were collected from all participants, and were subjected to RNA and DNA extractions for Real-time PCR and PCR tests. All PCR products were then sequenced to find T/C polymorphisms in the rs12252 region. Data on demographic, anthropometric, and clinical variables were collected from participants' medical records available in the primary care centers. The data was analyzed using DNASIS (v. 2.5) and Stata (v.11) software. RESULTS: All participants were of Fars ethnic background. The allele frequency for rs12252-C was found to be 9.49% among cases and 2.40% among controls. Carriers of the rs12252 C allele (CT + CC genotypes) showed 5.92 folds increase in the risk of mild flu comparing to the T allele homozygotes (P value: 0.007). We also found a significant positive association between rs12252 C allele heterozygote and mild flu (OR: 7.62, P value: 0.008), but not in C allele homozygote group (OR: 2.71, P value: 0.406). Similarly, we did not find a significant association between mild flu and BMI (OR: 1.06, P value: 0.087), diabetes (OR: 0.61, P value: 0.392), and hypercholesterolemia (OR: 0.50, P value: 0.393) in multivariable logistic regression. CONCLUSIONS: This is the first study evaluating the association between rs12252 polymorphisms, diabetes, hypercholesterolemia, and BMI and susceptibility to mild flu in an Iranian population. Our results suggest a significant positive association between mild flu and rs12252 C allele heterozygous and carriage. Future replication of the strong association observed here between rs12252 C allele carriage and mild flu might candidate this polymorphism as a genetic marker for early screening of susceptibility to mild flu. Lack of significant association between C allele homozygous and mild flu, observed in this study, might be the result of small sample size in this group. TRIAL REGISTRATION: IR.PII.REC.1395.3.

Helicobacter pylori Strains from Duodenal Ulcer Patients Exhibit Mixed babA/B Genotypes with Low Levels of BabA Adhesin and Lewis b Binding.

BACKGROUND: BabA is a Helicobacter pylori cell surface adhesin, which binds to the ABO/Le(b) histo-blood group antigens (Le(b)) and serves as a virulence factor. METHODS: H. pylori single colonies were isolated from 156 [non-ulcer dyspepsia (NUD) = 97, duodenal ulcer (DU) = 34, gastric cancer (GC) = 25)] patients. babA and babB genes were evaluated by gene/locus-specific PCR. BabA protein expression and Le(b) binding activity were determined by immunoblotting and ELISA, respectively. RESULTS: The combined categorization of H. pylori strains based on high, low or no levels of BabA expression and Le(b) binding, produced 4 groups: (I) BabA-high/Le(b)-high (36 %), (II) BabA-low/Le(b)-low (26 %), (III) BabA-neg/Le(b)-low (30 %) and (IV) BabA-neg/Le(b)-neg (8 %) strains. The majority (63 %) of the BabA-low/Le(b)-low strains exhibited mixed babA/B genotypes as compared to merely 18 % of the BabA-high/Le(b)-high, 15 % of the BabA-neg/Le(b)-neg and 11 % of the BabA-neg/Le(b)-low (P = 0.0001) strains. In contrast to NUD strains, the great majority (70 %) of DU strains were BabA-low/Le(b)-low (11 %, P = 0.0001), which compared to NUD strains, enhanced the risk of DU by 18.8-fold. In parallel, infection with babA/B mixed genotype strains amplified the risk of DU by 3.6-fold (vs. babA-positive: P = 0.01) to 6.9-fold (vs. babA-negative: P = 0.007). CONCLUSIONS: Here, we show higher prevalence of mixed babA/B genotypes among BabA-low/Le(b)-low clinical strains. Recombination of babA and babB genes across their loci may yield lower BabA expression and lower Le(b) binding activity. We conclude that H. pylori strains with lower Le(b) binding activity are better adapted for colonization of the gastric metaplastic patches in the duodenum and enhance the risk of duodenal ulcers.