Data availabilitySummary statistics generated by COVID-19 Host Genetics Initiative are available online (https://www.covid19hg.org/results/r6/). The analyses described here use the freeze 6 data. The COVID-19 Host Genetics Initiative continues to regularly release new data freezes. Summary statistics for samples from individuals of non-European ancestry are not currently available owing to the small individual sample sizes of these groups, but the results for 23 loci lead variants are reported in Supplementary Table 3. Individual-level data can be requested directly from the authors of the contributing studies, listed in Supplementary Table 1.

Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine’s neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. Methods: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. Results: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other’s effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). Conclusion: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

In patients with COVID‐19, certain medical conditions could result in poorer clinical outcomes. However, the prognostic role of hypothyroidism in COVID‐19 is still unknown. In the present retrospective study, we estimated the prevalence of hypothyroidism in COVID‐19 admitted patients in Tehran, Iran. Among 390 COVID‐19 admitted patients, 21 hypothyroid cases (5.4%) were found, in which nearly 90% were aged 50 years and older. Regarding the effect of hypothyroidism on COVID‐19 mortality, 60 (15.3%) of total patients and 4 (19%) of hypothyroid patients died, and no significant difference was found between the two groups.

Aims:We hypothesised that omega-3 fatty acids would be an appropriate adjunct therapy for alleviating the inflammatory response and clinical manifestation in hospitalised patients with Covid-19 disease. Methods: This was a single-blind randomised controlled trial in Amir-Alam hospital in Tehran. Thirty adult men and women diagnosed with Covid-19 were allocated to either control group (receiving Hydroxychloroquine) or intervention group (receiving Hydroxychloroquine plus 2 grams of Docosahexaenoic acid [DHA] + Eicosapentaenoic acid [EPA]) for 2 weeks. Primary outcome of the intervention including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as clinical symptoms including body pain, fatigue, appetite and olfactory and secondary outcomes including liver enzymes were determined at the baseline and after omega-3 supplementation. Clinical signs were measured using self-reported questionnaires. There were commercial kits for determination of CRP and liver enzymes concentrations in the serum of patients. For determination of ESR automated haematology analyser was applied. The study of "Comparison of the effectiveness of omega-3 and Hydroxychloroquine on Inflammatory factors, liver enzymes and clinical symptoms in diabetic Covid-19 patients" was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20200511047399N1. Results:In comparison to control group, patients receiving omega-3 indicated favourable changes in all clinical symptoms except for olfactory (P < .001 for body pain and fatigue, P = .03 for appetite and P = .21 for olfactory). Reducing effects of omega-3 supplementation compared with control group were also observed in the levels of ESR and CRP after treatment (P < .001 for CRP and P = .02 for ESR).However, no between group differences in the liver enzymes serum concentrations were observed after supplementation (P > .05). Conclusion:Current observations are very promising and indicate that supplementation with moderate dosages of omega-3 fatty acids may be beneficial in the management of inflammation-mediated clinical symptoms in Covid-19 patients.

Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

Avian infectious bronchitis (IB) is a worldwide chicken disease, caused by avian infectious bronchitis virus (IBV) which infects all commercial poultry lines. The present study was done to evaluate protection caused by two different serotype vaccines (Massachusetts and 793/B) in order to evaluate protection against challenge with IS/1494/06-like virus (variant 2-like virus), which is prevalent in the Middle East. SPF chickens were divided into four groups (n = 20). First and second group as negative control group and non-vaccinated-challenged group received no vaccine. Groups 3 and 4 received H120-H120 and H120-1/96 IBV vaccine strains at the 1st and 14th day, respectively. Twenty one days after last vaccination, non-vaccinated-challenged group and vaccinated group were challenged using variant 2-like IBV. Serum samples were collected before challenge to measure humoral immune response of chickens. Five days after challenge, the tissue samples from the trachea, lungs and kidneys were taken to evaluate cilliary activity, viral load (quantitative real-time RT-PCR), and histopathological evaluation. Clinical sign scores were also recorded after challenge. Overall, the results showed a protective efficacy of the used vaccination program. Best cross protection (69.2%) was obtained in the H120-1/96 vaccinated group. Virus replication of the challenged virus in H120-1/96 group compared with H120-H120 group showed a significant reduction of viral load in trachea (1.5×103 compared to 503) and kidneys. Clinical sign scores of the challenged groups showed significant effect of the vaccination program to reduce clinical signs. The trachea pathological scores and histopathological findings in the lungs and kidneys also confirmed better protective efficacy of vaccinated groups. In conclusion, using combination of heterologous IBV vaccine serotypes (Massachusetts and 793/B) would be a better strategy to control variant 2-like viruses, but more evaluation is needed using other circulating isolates to find the best combination of vaccines.

In 2010, H5N8 highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage dramatically affected poultry and wild birds in Asia, Europe, and North America. In November 2016, HPAI H5N8 was detected in a commercial layer farm in Tehran province. The diagnosis was based on real-time reverse transcriptase PCR (RRT-PCR) and sequencing of haemaglutinin (HA) and neuraminidase (NA) genes from suspected samples. Genetic and phylogenetic analysis of the HA gene demonstrated that the Iranian HPAI H5N8 viruses belong to the HPAI H5 virus clade 2.3.4.4 and cluster within group B (Gochang-like). In particular, the highest similarity was found with the sequences of the HPAI H5N8 identified in Russia in 2016. To our knowledge, this clade has not been previously detected in Iran. Previous HPAI A (H5) epidemic in Iran occurred in 2015 and involved exclusively viruses of clade 2.3.2.1c. These findings indicate that Iran is at high risk of introduction of HPAI H5 of the A/Goose/Guangdong/1/1996 lineage from East Asia and highlight the need to maintain adequate monitoring activities in target wild and domestic bird species for HPAI early detection. This study is useful for better understanding the genetic and antigenic evolution of H5 HPAI viruses in the region and the world.

Background: Studies have shown that CT could be valuable for prognostic issues in COVID-19. Objectives: To investigate the prognostic factors of early chest CT findings in COVID-19 patients. Methods: This retrospective study included 91 patients (34 women, and 57 men) of real-time reverse transcription polymerase chain reaction (RT-PCR) positive COVID-19 from three hospitals in Iran between February 25, 2020, to March 15, 2020. Patients were divided into two groups as good prognosis, discharged from the hospital and alive without symptoms (48 patients), and poor prognosis, died or needed ICU care (43 patients). The first CT images of both groups that were obtained during the first 8 days of the disease presentation were evaluated considering the pattern, distribution, and underlying disease. The total CT-score was calculated for each patient. Univariate and multivariate analysis with IBM SPSS Statistics v.26 was used to find the prognostic factors. Results: There was a significant correlation between poor prognosis and older ages, dyspnea, presence of comorbidities, especially cardiovascular and comorbidities. Considering CT features, peripheral and diffuse distribution, anterior and paracardiac involvement, crazy paving pattern, and pleural effusion were correlated with poor prognosis. There was a correlation between total CT-score and prognosis and an 11.5 score was suggested as a cut-off with 67.4% sensitivity and 68.7% specificity in differentiation of poor prognosis patients (patients who needed ICU admission or died). Multivariate analysis revealed that a model consisting of age, male gender, underlying comorbidity, diffused lesions, total CT-score, and dyspnea would predict the prognosis better. Conclusions: Total chest CT-score and chest CT features can be used as prognostic factors in COVID-19 patients. A multidisciplinary approach would be more accurate in predicting the prognosis.