Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

SARS-CoV-2 genome surveillance projects provide a good measure of transmission and monitor the circulating SARS-CoV-2 variants at regional and global scales. Iran is one of the most affected countries still involved with the virus circulating in at least five significant disease waves, as of September 2021. Complete genome sequencing of 50 viral isolates in an early phase of outbreak in Iran, shed light on the origins and circulating lineages at that time. As part of a genomic surveillance program, we provided an additional 319 complete genomes from October 2020 onwards. The current study is the report of complete SARS-CoV-2 genome sequences of Iran in the March 2020-May 2021 time interval. We aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year. Overall, 35 different lineages and 8 clades were detected. Temporal dynamics of the prominent SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and introduces 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) clades, dominating second, third and fourth disease waves, respectively. We observed a mixture of circulating 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades in winter 2021, paralleled in a diminishing manner for 20A/20B and a growing rise for 20I, eventually prompting the 4th outbreak peak. Furthermore, our study provides evidence on the entry of the Delta variant in April 2021, leading to the 5th disease wave in summer 2021. Three lineages are highlighted as hallmarks of SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (specific B.1.1 lineage carrying a combination of [D138Y-S477N-D614G] spike mutations) in October 2020-February 2021, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. Continuous monthly monitoring of SARS-CoV-2 genome mutations led to the detection of 1577 distinct nucleotide mutations, in which the top recurrent mutations were D614G, P323L, R203K/G204R, 3037C>T, and 241C>T; the renowned combination of mutations in G and GH clades. The most frequent spike mutation is D614G followed by 13 other frequent mutations based on the prominent circulating lineages; B.1.1.7 (H69_V70del, Y144del, N501Y, A570D, P681H, T716I, S982A, D1118H, I100T, and L699I), B.1.1.413 (D138Y, S477N) and B.1.36 (I210del). In brief, mutation surveillance in this study provided a real-time comprehensive picture of the SARS-CoV-2 mutation profile in Iran, which is beneficial for evaluating the magnitude of the epidemic and assessment of vaccine and therapeutic efficiency in this population.

Two independent introductions of SARS-CoV-2 into the Iranian outbreak

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence, with now more than one million deaths around the world. While Iran was among the first countries confronted with rapid spread of virus in February, no real-time SARS-CoV-2 whole-genome tracking is 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, 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 occurred around 26 December 2019, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission, 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. According to possible role of D614G in increased infectivity and transmission of the virus, and considering the current high prevalence of the disease, dominancy of this lineage may push the country into a critical health situation. Therefore, current data warns for considering stronger prohibition strategies preventing the incidence of larger crisis in future.

Magnesium sulfate ameliorates carbon monoxide­induced cerebral injury in male rats.

Carbon monoxide (CO) has been shown to induce several cardiovascular abnormalities, as well as necrosis, apoptosis and oxidative stress in the brain. Magnesium sulfate (MS) has been shown to have beneficial activities against hypoxia in the brain. In the present study, the possible protective effects of MS against CO­induced cerebral ischemia were investigated. For this purpose, 25 male Wistar rats were exposed to 3,000 ppm CO for 1 h. The animals were divided into 5 groups (n=5 in each group) as follows: The negative control group (not exposed to CO), the positive control group (CO exposed and treated with normal saline), and 3 groups of CO­exposed rats treated with MS (75, 150 and 300 mg/kg/day) administered intraperitoneally for 5 consecutive days. On the 5th day, the animals were sacrificed and the brains were harvested for the evaluation of necrosis, apoptosis and oxidative stress. Histopathological evaluation revealed that MS reduced the number and intensity of necrotic insults. The Bax/Bcl2 ratio and malondialdehyde (MDA) levels were significantly decreased in a dose­dependent manner in the MS­treated rats compared to the positive control group, while a significant dose­dependent increase in Akt expression, a pro­survival protein, was observed. In addition, MS administration reduced pro­apoptotic indice levels, ameliorated histological insults, favorably modulated oxidative status and increased Akt expression levels, indicating a possible neuroprotective effect in the case of CO poisoning. On the whole, the findings of this study indicate that MS may prove to be useful in protecting against CO­induced cerebral injury.

Celiac disease: Serologic prevalence in patients with irritable bowel syndrome.

BACKGROUND: The prevalence of irritable bowel syndrome (IBS) in the community is 10%-20% and have symptom based diagnostic criteria. Many symptoms of celiac disease (CD) with 1% prevalence in some communities can mimic IBS. Sensitive and specific serologic tests of CD can detect asymptomatic cases. The purpose of this study was to compare the level of anti-tissue-transglutaminase (tTG) IgA in IBS patients and controls group. MATERIALS AND METHODS: This case-control study was performed at a University hospital in which 107 patients with IBS who met the Rome II criteria for their diagnosis were compared with 126 healthy age and sex-matched controls. Both groups were investigated for CD by analysis of their serum tTG IgA antibody with human recombinant antigen. Titers were positive containing over 10u/ml and borderline if they were between 4 and 10 u/ml. RESULT: 86 percent of IBS patients were female. The mean antibody level was 0.837 u/ml in IBS group and 0.933 u/ml in control group without any significant difference. DISCUSSION AND CONCLUSION: Results of this study may intensify disagreement on the situation of CD in IBS patients.