The Association Between Genetic Variants in ACE1and ACE2 Genes with Susceptibility to COVID-19 Infection.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Role of host immunity and HBx among inactive chronic hepatitis B patients in a highly endemic region.

The hepatitis B virus (HBV) infection has a wide range, from fulminant hepatitis to inactive chronic hepatitis B (ICB) infection. The present study evaluated critical factors in the outcomes of HBV infection in a highly endemic region of Iran (approximately 12% HBV positive). The expression of seven genes involved in host immunity (Foxp3, T-bet, ROR-γt, AKT, CREB, IL-28/or IFN-λ2, and IL-28R) and HBx for viral activities were evaluated using real-time PCR, TaqMan method. A total of 58 subjects were randomly chosen, including 28 ICB and 30 healthy controls (HCs) from the Esfandiar district, South Khorasan province, Iran. The expression index of Foxp3 and ROR-γt was moderately up-regulated in ICBs but did not statistically significant. T-bet expression in ICB patients was significantly higher than in HCs (p = 0.004). Furthermore, evaluating two signalling pathways in Th activation and cell survival showed that the CREB pathway was significantly up-regulated in ICB patients compared to HCs (p = 0.006), but the AKT did not differ. In innate immune responses, the IL-28/or IFN-λ2 expression in ICB patients was significantly higher than in the HCs (p = 0.02). Surprisingly, only one ICB patient disclosed HBx expression, which shows deficient virus activity in these patients. The ICB condition seems to result from host immune pressure on HBV activities, up-regulation of T-bet and IFN-λ. The high expression of CREB may prevent Kupffer's pro-inflammatory reactions in the liver. Whereas the absence of HBx expression in ICB patients and, consequently, the inactivity of HBV may also confirm such immune pressure.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Toxoplasma gondii infection as a potential risk for chronic liver diseases: A systematic review and meta-analysis.

Toxoplasma gondii, the etiological agent of toxoplasmosis, can cause serious public health problems. Although Toxoplasma gondii tends more to neurotropic and ocular organs, some existing evidence suggest that this disease might induce serious pathological effects on liver. Hence, this study aimed to evaluate the relationship between chronic liver diseases and toxoplasmosis. Meanwhile, it attempted to assess whether patients with toxoplasmosis are susceptible to chronic liver diseases. To achieve this aim, the published studies related to the subject were systematically searched in five major electronic databases between the January 1, 1950 and October 1, 2019. The meta-analysis was carried out using the StatsDirect statistical software and a p-value less than 0.05 was considered significant for any test. Out of 691 identified studies, 10 studies met our inclusion criteria and entered this systematic review. The pooled prevalence rates of Toxoplasma gondii in patients with liver diseases (35.97%; 95% CI: 28.38-43.93) were higher than those in the control group (18.24%; 95% CI: 13.85-23.09). The meta-analysis indicated that the common Odd Ratio by a random effect model was 2.7 (95% CI: 2.30-3.24), revealing a significant association between chronic liver diseases and anti-Toxoplasma IgG antibody. The results of this systematic review confirmed the positive connection between toxoplasmosis and chronic liver diseases. Nonetheless, more studies are needed to clarify the detailed association between these diseases.

Epidemiology, risk factors, and molecular characterization of occult hepatitis B infection among anti-hepatitis B core antigen alone subjects.

OBJECTIVES: Features of occult hepatitis B virus (HBV) infection among the anti-hepatitis B core antigen (anti-HBc) positives have yet to be described in more details. This study aimed to determine the molecular prevalence of occult HBV infection (OBI), and association to risk factors among seropositives for anti-HBc. METHODS: This was part of a community-based screening project that included 5234 cases. All participants completed a questionnaire on demographic and socio-epidemiological information. Then, the blood samples were collected and tested for anti-HBc and HBsAg using ELISA method. To identify OBI, nested-polymerase chain reaction (PCR) assays were performed for HBV-S and X genes, and viral load was determined using an in-house real-time PCR. Sequencing and phylogenetic analysis have been implemented for genotyping. RESULTS: Overall, 596 cases, positive only for anti-HBc were included in the study. OBI was detected among 61 cases (10.2%). The genotype and subgenotype of HBV among all of them was D1, except one that was D4. Most of them had low viral loads ranged from 1.2 × 102 to 1.34 × 10 3 copies/mL; 19.6% had undetectable viral loads. Important mutations in surface protein and reverse transcriptase were sI92T, sQ129H, rtL80I, rtS85F, rtL91I. The prevalence of OBI was related to some risk factors, such as tattooing (P = 0.02), sexual activities (P = 0.009), and diabetes (P = 0.031). CONCLUSION: Our study suggests that OBI should be considered among anti-HBc seropositive subjects. This form of HBV infection was accompanied with some mutations, risk factors, and diseases. However, further investigations are needed to determine virological importance of documented mutations.

Molecular and serological characterization of occult hepatitis B virus infection among patients with hemophilia.

BACKGROUND: The occult hepatitis B virus infection (OBI) is a health concern among high-risk groups and immunosuppressed individuals. There is still a paucity of data regarding the occult hepatitis B virus infection among hemophilic patients. With this in mind, we aimed to evaluate the molecular prevalence of OBI among clients with hemophilia. METHODS: Totally, 87 hemophilic patients were selected to be studied. To detect OBI, nested polymerase chain reaction test was used to amplify HBV-S, X, and Core regions. Viral load was determined using an in-house real-time PCR assay. Finally, sequence of S gene was used for genotyping and analysis of mutations. RESULTS: The mean age of patients was 28.4 ± 5.3 years old, with 90.7% of whom were men. HBV-DNA was detected in eight subjects (9.3%). The rate of OBI was much higher in anti-HBs seronegative subjects than that in other patients (P = 0.019). All OBI cases had HBV genotype D, subgenotype D1. In addition, five out of eight cases (62.5%) showed detectable viral loads (a mean viral load of 4.5 × 10 2 copies/mL). sR73H, sI110L, sP120A, sP127T, sQ129H, sG130R, and sC137S were shown to be the most determinant escape mutation and OBI-relevant mutants. CONCLUSION: The rate of OBI among the studied population of hemophilia seems to be remarkable. Therefore, screening for OBI must be a routine practice in patients with hemophilia and also patients undergoing immunosuppressive treatments. Amino acid substitutions were observed in the major hydrophilic region. However further investigations are needed for analysis of exact function.

Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran.

Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95% credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs.

The prevalence of HTLV-1 and its Co-Infection with HCV, HBV and HIV in Hemophilic patients.

BACKGROUND AND OBJECTIVE: Blood-borne infections, such as the HIV virus and hepatitis B and C, are major problems in patients receiving blood products. Here we examined the prevalence of HTLV-1, HCV, HBV, and HIV in hemophilic patients. METHODS: A cross-sectional study on 108 hemophilic patients (101 males and 7 females) involved detection of HBV, HCV, HIV and HTLV-1 infections using immunoassays for HBsAg, hepatitis B core antibodies (anti-HBc), hepatitis C antibodies (anti-HCV), HIV antibodies (anti-HIV) and Anti-HTLV-1. Real-time PCR was used to measure HCV RNA, and HCV genotyping was performed by direct sequencing of the 5' noncoding region. RESULTS: Hemophilia A was reported in 93 (86%) patients with severe symptoms in 8 cases. The seroprevalence of anti-HCV and anti-HTLV-1 antibodies was 20% and 3% respectively. One patient with severe hemophilia had a HCV/HTLV-1 co-infection. HCV-RNA was detected in 82% of patients. In terms of genotyping prevalence was 56% HCV genotype 3a, 39% HCV genotype 1a, and 6% HCV genotype2. Anti HIV and HBsAg were not detected in any patient. HTLV1 prevalence was higher, HCV lower in South Khorasan than other regions in Iran or elsewhere. CONCLUSION: Management of transfusion of blood and blood products should account for the underlying prevalence of infectious agents.

A multicenter study of severity and prognosis of symptomatic COVID-19 in end-stage renal disease and non-dialysis patients in East of Iran.

OBJECTIVES: This study aimed to assess the severity and related factors of symptomatic COVID-19 in end-stage renal disease (ESRD) patients from several centers in Eastern Iran. METHODS: In this retrospective cohort study, after obtaining ethical approval, 410 patients diagnosed with COVID-19 were included for analysis. Patients were categorized into two groups based on their dialysis status: the dialysis group (ESRD patients undergoing hemodialysis) and the non-dialysis group (those without chronic dialysis). Demographic information, clinical symptoms, laboratory tests at admission, length of hospitalization, ICU admission, need for mechanical ventilation, and mortality data were extracted from their medical records and entered into researcher-developed checklists. RESULTS: In this multicenter study, 104 dialysis patients with a mean age of 64.81 ± 16.04 were compared to 316 non-dialysis patients with a mean age of 60.92 ± 17.89. Patients were similar in terms of age and gender, but a higher percentage of the dialysis group was aged over 65 years (p = .008). Altered consciousness, dyspnea, headache, myalgia, anorexia, and cough were statistically significantly more common in the dialysis group when evaluating clinical symptoms (p < .05). The dialysis group had significantly higher levels of white blood cell (WBC), potassium, calcium, urea, creatinine, blood pH, INR, ALT, ESR, and CRP, and lower levels of red blood cell, Hb, platelets, sodium, and LDH compared to the non-dialysis group. Profoundly altered consciousness was more common among deceased patients (p < .001), and this group had higher WBC counts, urea levels, AST, ALT (p < .05), and lower blood pH (p = .001). CONCLUSION: Based on the results of this study, it is plausible to suggest a hypothesis of greater severity and worse prognosis of COVID-19 in ESRD patients. Underlying comorbidities, such as liver disorders or more severe clinical symptoms like altered consciousness, may also be indicative of a worse prognosis in dialysis patients with COVID-19.

Unpacking HPV Stigma: Assessing Healthcare Workers' Knowledge and Stigma Towards HPV While Exploring the Connection Between the Two.

Objectives: Human Papillomavirus (HPV) is a leading cause of cervical cancer, yet existing social stigmas and unequal access to healthcare compromise its preventability through screening and vaccination. Understanding healthcare professionals' knowledge and perceptions of HPV is pivotal in enhancing the quality and effectiveness of preventive healthcare strategies. This article aims to explore and understand the relationship between healthcare workers' knowledge and stigma towards HPV. Design and Methods: A questionnaire of 27 stigma and 24 knowledge questions was provided for healthcare personnel. Demographic questions were also included. Stigma levels were determined based on a total median score. Fully adjusted multinomial logistic regression models were used to find the correlation between knowledge regarding HPV and the stigma level. Results: Five hundred fifty-two healthcare workers answered the questionnaire. The findings showed that while most participants had adequate to moderate knowledge about the prevention and complications of HPV, they lacked knowledge about symptoms and treatment. Stigma towards HPV disease was evident in some participants, with attitudes varying depending on demographic factors and knowledge level. The model indicated that age, gender, and specific knowledge questions were significantly associated with stigma levels. Interestingly, the presence of knowledge in some areas increased the stigma level. Conclusions: In conclusion, the study sheds light on the stigmatization and knowledge gaps regarding HPV disease among healthcare personnel and, intriguingly, that increased knowledge does not necessarily correlate with decreased stigma. The findings highlight the need for targeted education and training programs to improve healthcare providers' knowledge in these specific areas.

The Impact of Pulmonary Hydatid Cyst Rupture on COVID-19 Symptom Severity.

BACKGROUND: Co-infection with other microorganisms such as parasites in patients with COVID-19 can affect the clinical outcome and require prompt diagnosis and appropriate therapy. CASE PRESENTATION: We present a case of an adult male with chest pain, dyspnea, cough, diplopia, and anorexia who was confirmed to have acute COVID-19 pneumonia. 2 weeks prior to admission, a hydatid lung cyst was identified on examination, but the patient refused surgery. Thoracoabdominal computed tomography (CT) revealed a rupture of the lung hydatid cyst and co-infection with COVID-19. The patient has prescribed a treatment protocol for COVID-19 and albendazole. Despite measures taken to manage severe inflammation and decreasing blood oxygen levels, the patient required admission to the intensive care unit (ICU) and intubation. After approximately 3 weeks of hospitalization, the patient was successfully extubated and discharged uneventfully from the hospital. Oral albendazole was prescribed for follow-up treatment. CONCLUSION: Our case highlights the importance of considering hydatid cysts in the differential diagnosis of patients with COVID-19, especially those living in endemic areas.

Differences in clinical and lab characteristics of sepsis between opium user patients and patients with no illicit drug addiction.

BACKGROUND: Sepsis is a significant cause of mortality worldwide. This study aimed to compare clinical and laboratory characteristics of sepsis in patients addicted to illicit drugs versus patients with no illicit drug addiction. METHODS: In this cross-sectional study, all patients hospitalized with sepsis diagnosis were recruited within six months from September to March 2019. Sixty patients for each group (illicit drug-addicted and non-addicted individuals) were selected. The data relating to illicit drug consumption, serum indices, the current focus of infection, duration of hospitalization, and disease outcomes were collected. Patients who had an illicit drug addiction were compared with non-addicted patients in terms of clinical and laboratory parameters. The data collected were analyzed using SPSS software (version 19). RESULTS: The bacterial load in the urine culture was statistically significant in both groups and higher in the non-addicted group. The frequency distributions of focus of infection, duration of hospitalization, and outcome were not significantly different between the two groups. The serum sodium and total neutrophils were significantly higher in the addicted group. However, the MCHC level was significantly lower (p<0.05). CONCLUSION: Opium may have stimulated the immune system and reduced bacterial infection in septic patient users.

SARS-COV-2 IgG specific antibodies persistence in recovered COVID-19 individuals and its association with severity and time of illness.

In order to accurately interpret the immune response to COVID-19, it is critical to know how long serum antibodies to COVID-2 persist. This study aimed to describe the serum IgG responses to SARS-CoV-2 in patients with mild, moderate, and severe COVID-19 infection in Birjand, South Khorasan province, Iran. The study was performed on individuals whose COVID-19 disease was confirmed by RT-PCR and recovered from the disease. After completing the questionnaire, blood samples were collected from 4 different groups based on the time of the test at two, four, six, and eight months' post-recovery. Then, SARS-COV-2 virus-specific IgG nucleocapsid antibody level in patients was measured using the enzyme-linked immunosorbent assay (ELISA). In total, 206 patients (mean age 44.19 ± 14.9, 51% man) were included in the survey. Serum prevalence of specific IgG antibodies in patients with mild, moderate, and severe COVID-19 disease was 51.5%, 64% and 78.9%, respectively. Furthermore, serum prevalence of COVID-19 specific IgG antibody level in two, four, six, and eight months after recovery were 80.8, 69.1, 43.2 and 41.8%, respectively (p < 0.05). The multiple logistic regression model showed that the variables of age and the time elapsed after recovery had a significant relationship with the positive antibody test of recovered COVID-19 patients (P < 0.05). But other variables had no significant relationship with the result of antibody test (P > 0.05). In the present report, we attempted to characterize the antibody response against SARS-CoV-2 in patients with mild, moderate, and severe COVID-19, with the aim of better elucidating the humoral immune response after recovery from SARS-CoV-2 infection.

Implementation of an In-House Platform for Rapid Screening of SARS-CoV-2 Genome Variations.

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.

Survival Evaluation of Hospitalized COVID-19 Patients with Cox Frailty Approach.

INTRODUCTION: The survival cox analysis is becoming more popular in time-to-event data analysis. When there are unobserved /unmeasured individual factors, then the results of this model may not be dependable. Hence, this study aimed to determine the factors associated with Covid-19 patients' survival time with considering frailty factor. METHODS: This study was conducted at 1 of the hospitals in Iran, so that hospitalized patients with COVID-19 were included. Epidemiological, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. Gamma-frailty Cox model was used to identify the effects of the risk factors. RESULTS: A total of 360 patients with COVID-19 enrolled in the study. The median age was 74 years (IQR 61 - 83), 903 (57·7%) were men, and 661 (42·3%) were women; the mortality rate was 17%. The Cox frailty model showed that there is at least a latent factor in the model (P = 0.005). Age and platelet count were negatively associated with the length of stay, while red blood cell count was positively associated with the length of stay of patients. CONCLUSION: The Cox frailty model indicates that in addition to age, the frailty factor is a useful predictor of survival in Covid-19 patients.

A family cluster of cutaneous Leishmania major infection unresponsive to intralesional meglumine antimonial: Case reports.

We describe a family cluster of L. major that became infected by traveling to an endemic focus of CL, which did not respond to intralesional meglumine antimonial treatment whilst two were hospitalized due to the progressive disease that responded to 4 weeks of oral ketoconazole. Parasite genotyping of the internal transcribed spacer 1 gene revealed the same infecting parasite strain in all family members and was the same strain in GenBank that caused mucosal L. major in a tourist who visited several North African countries. We hypothesise a reduced host immune response in the two hospitalized patients.

Seroprevalence of SARS-COV-2 antibodies among health-care workers exposed to COVID-19 patients in a large reference hospital, Iran.

Background and Objectives: Health care workers (HCWs) are a high-risk group for acquiring and transmitting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Aim of the study was the evaluation of seroprevalence of SARS-CoV-2 in a random sample of HCWs at a large acute care hospital in Iran. Materials and Methods: We collected blood samples of 180 medical staffs from September 22, 2020 to January 26, 2021. The enzyme linked immunosorbent assays (ELISA) tests were used for evaluation of the presence of IgG antibodies. Participants completed a self-report questionnaire, comprising demographics, occupational, the work area, and personal protection data. Results: Of the 180 HCWs who participated in this study, 44 (24.4%) were seropositive for anti-SARS-CoV-2 IgG. The percentage of IgG positivity was higher in males than females (P<0.05). Also, there was statistically significant difference between presence of the antibodies and the occupation, location, and infecting family members with Covid -1 (P<0.05). Other factors did not associate significantly to antibody presence against SARS-CoV-2 (P>0.05). Conclusion: According to this point that the number of COVID-19 cases is still growing rapidly among HCWs. So, the epidemiological estimate of SARS-CoV-2 infection remains a major challenge that is needed to prevent the spread of infection in the hospitals.

SARS-CoV-2 outbreak in Iran: The dynamics of the epidemic and evidence on two independent introductions.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.

Disease Waves of SARS-CoV-2 in Iran Closely Mirror Global Pandemic Trends.

BACKGROUND: Complete SARS-CoV-2 genome sequencing in the early phase of the outbreak in Iran showed two independent viral entries. Subsequently, as part of a genome surveillance project, we aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year after emerging. METHODS: We provided 319 SARS-CoV-2 whole-genome sequences used to monitor circulating lineages in March 2020-May 2021 time interval. RESULTS: The temporal dynamics of major SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and represent the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7), leading the second, third and fourth waves, respectively. We observed a mixture of circulating B.1.36, B.1.1.413, B.1.1.7 lineages in winter 2021, paralleled in a fading manner for B.1.36/B.1.1.413 and a growing rise for B.1.1.7, prompting the fourth outbreak. Entry of the Delta variant, leading to the fifth disease wave in summer 2021, was detected in April 2021. This study highlights three lineages as hallmarks of the SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (B.1.1 with the combination of [D138Y-S477N-D614G] spike mutations) as a characterizing lineage in Iran, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. It also designates the renowned combination of G and GR clades' mutations as the top recurrent mutations. CONCLUSION: In brief, we provided a real-time and comprehensive picture of the SARS-CoV-2 genetic diversity in Iran and shed light on the SARS-CoV-2 transmission and circulation on the regional scale.