Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study.

BACKGROUND: The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. METHODS: This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. RESULTS: The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. CONCLUSIONS: Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.

Dynamics of the COVID-19 Clinical Findings and the Serologic Response.

The factors affecting the dynamics of lengthening of symptoms and serologic responses are not well known. In order to see how the serologic responses change in relation to the clinical features, we selected a group of 472 adults with a positive IgM/IgG antibody test result from a baseline study of the anti-SARS-CoV-2 seropositivity, assessed their COVID-19 and past medical histories, and followed them up in about 3 months. Nearly one-fourth of the subjects were asymptomatic at the baseline; 12.8% subjects became symptomatic at the follow-up (FU) when 39.8% of the subjects had some persisting symptoms. At the baseline, 6.1% showed anti-SARS-CoV-2 IgM positive, 59.3% only for IgG, and 34.5% for both. At the FU, these figures declined to 0.6, 54.0, and 4.4%, respectively, with the mean IgM and IgG levels declining about 6.3 and 2.5 folds. Blood group A was consistently linked to both sustaining and flipping of the gastrointestinal (GI) and respiratory symptoms. The baseline IgM level was associated with GI symptoms and pre-existing cirrhosis in multivariate models. Both of the baseline and FU IgG levels were strongly associated with age, male, and lung involvement seen in chest computed tomography (CT)-scan. Finally, as compared with antibody decayers, IgM sustainers were found to be more anosmic [mean difference (MD): 11.5%; P = 0.047] with lower body mass index (BMI) (MD: 1.30 kg/m2; P = 0.002), while IgG sustainers were more commonly females (MD: 19.2%; P = 0.042) with shorter diarrhea duration in the FU (MD: 2.8 days; P = 0.027). Our findings indicate how the anti-SARS-CoV-2 serologic response and COVID-19 clinical presentations change in relation to each other and basic characteristics.

SARS-CoV-2 antibody seroprevalence in the general population and high-risk occupational groups across 18 cities in Iran: a population-based cross-sectional study.

BACKGROUND: Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate. METHODS: In this population-based cross-sectional study, we randomly selected and invited study participants from the general population (from lists of people registered with the Iranian electronic health record system or health-care centres) and a high-risk population of individuals likely to have close social contact with SARS-CoV-2-infected individuals through their occupation (from employee lists provided by relevant agencies or companies, such as supermarket chains) across 18 cities in 17 Iranian provinces. Participants were asked questions on their demographic characteristics, medical history, recent COVID-19-related symptoms, and COVID-19-related exposures. Iran Food and Drug Administration-approved Pishtaz Teb SARS-CoV-2 ELISA kits were used to detect SARS-CoV-2-specific IgG and IgM antibodies in blood samples from participants. Seroprevalence was estimated on the basis of ELISA test results and adjusted for population weighting (by age, sex, and city population size) and test performance (according to our independent validation of sensitivity and specificity). FINDINGS: From 9181 individuals who were initially contacted between April 17 and June 2, 2020, 243 individuals refused to provide blood samples and 36 did not provide demographic information and were excluded from the analysis. Among the 8902 individuals included in the analysis, 5372 had occupations with a high risk of exposure to SARS-CoV-2 and 3530 were recruited from the general population. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17·1% (95% CI 14·6-19·5), implying that 4 265 542 (95% CI 3 659 043-4 887 078) individuals from the 18 cities included were infected by the end of April, 2020. The adjusted seroprevalence of SARS-CoV-2-specific antibodies varied greatly by city, with the highest estimates found in Rasht (72·6% [53·9-92·8]) and Qom (58·5% [37·2-83·9]). The overall population weight-adjusted and test performance-adjusted seroprevalence in the high-risk population was 20·0% (18·5-21·7) and showed little variation between the occupations included. INTERPRETATIONS: Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected. The potential shortcomings of current public health policies should therefore be identified to prevent future epidemic waves in Iran. FUNDING: Iranian Ministry of Health and Medical Education. TRANSLATION: For the Farsi translation of the abstract see Supplementary Materials section.

Molecular dynamics analysis predicts ritonavir and naloxegol strongly block the SARS-CoV-2 spike protein-hACE2 binding.

The rapid emergence of COVID-19 pandemics has posed humans particularly vulnerable to the novel SARS-CoV-2 virus. Since de novo drug discovery is both expensive and time-consuming, drug repurposing approaches are believed to be of particular help. The SARS-CoV-2 spike (S) protein is known to attach human angiotensin-converting enzyme-2 (hACE2) through its receptor-binding domain (RBD). We screened 1930 FDA-approved ligands for the selection of optimal ones blocking this interaction. Virtual screening predicted top 25 ligands docking to any of the reported binding sites. After exclusion of those ligands which were unsuitable for systemic use, the remaining 69 RBD-ligand complexes were screened based on the masking capacity of the amino acid residues engaged in RBD-hACE2 interaction, excluding 47 RBD-ligand complexes. A short molecular dynamics (MD) simulation analysis identified 11 globally stable complexes with the lowest RMSD (root-mean-square deviation). Next, a moderately long MD analysis revealed those six RBD-ligand complexes with the lowest RMSD variation, as a measure of global stability. Finally, a long MD analysis revealed two select candidate ligands, including ritonavir and naloxegol, highly stabilizing those key residues engaged in RBD-hACE2 interaction. A similar MD analysis of a few antiviral drugs which are under clinical trials or approved for COVID-19 treatment showed them inferior to both select ligands in terms of stabilizing the RBD globally and locally at binding sites. Because of the crucial role of the S protein in virus virulence, our results highly propose ritonavir and naloxegol as the potentially helpful therapeutics against COVID-19, mandating appropriate clinical trials.Communicated by Ramaswamy H. Sarma.