Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Excess deaths during the COVID-19 pandemic in Iran.

BACKGROUND: The actual number of deaths during the COVID-19 pandemic is expected to be higher than the reported deaths. We aimed to estimate the number of deaths in Iran during the COVID-19 pandemic from December 22, 2019 to March 20, 2022. METHODS: We compared the number of age- and sex-specific deaths reported by Iran's Bureau of Vital Statistics with the predicted deaths estimated using an improved Lee-Carter model. We estimated the number of all-cause excess deaths in three scenarios, including the baseline scenario (without any undercounting of deaths) and 4% and 8% undercounting of all-cause deaths. RESULTS: We estimated 282,378 (95% confidence intervals [CI]: 225,439; 341,951) excess deaths in the baseline model. This number was 303,148 (95% CI: 246,417; 357,823) and 308,486 (95% CI: 250,607; 364,417) in the 4% and 8% scenarios, respectively. During the same period, Iran reported 139,610 deaths as being directly related to COVID-19. The ratio of reported COVID-19 deaths to total excess deaths ranged from 45.2% to 49.4% in the various scenarios. Most excess deaths occurred in the baseline scenario in males (157,552 [95% CI: 125,142; 191,265]) and those aged ≥75 years (102,369 [95% CI: 93,894; 111,188]). CONCLUSIONS: The reported number of COVID-19 deaths was less than half of Iran's estimated number of excess deaths. The results of this study will be helpful for health policymakers' planning, and call for strengthening the timeliness and accuracy of Iran's death registration systems, planning for more accurate monitoring of epidemics, and planning to provide support services for survivors' families.

Estimating the Number of COVID-19 Cases and Impact of New COVID-19 Variants and Vaccination on the Population in Kerman, Iran: A Mathematical Modeling Study.

COVID-19 is spreading all over Iran, and Kerman is one of the most affected cities. We conducted this study to predict COVID-19-related deaths, hospitalization, and infected cases under different scenarios (scenarios A, B, and C) by 31 December 2021 in Kerman. We also aimed to assess the impact of new COVID-19 variants and vaccination on the total number of COVID-19 cases, deaths, and hospitalizations (scenarios D, E, and F) using the modified susceptible-exposed-infected-removed (SEIR) model. We calibrated the model using deaths reported from the start of the epidemic to August 30, 2021. A Monte Carlo Markov Chain (MCMC) uncertainty analysis was used to estimate 95% uncertainty intervals (UI). We also calculated the time-varying reproductive number (R t) following time-dependent methods. Under the worst-case scenario (scenario A; contact rate = 10, self-isolation rate = 30%, and average vaccination shots per day = 5,000), the total number of infections by December 31, 2021, would be 1,625,000 (95% UI: 1,112,000-1,898,000) with 6,700 deaths (95% UI: 5,200-8,700). With the presence of alpha and delta variants without vaccine (scenario D), the total number of infected cases and the death toll were estimated to be 957,000 (95% UI: 208,000-1,463,000) and 4,500 (95% UI: 1,500-7,000), respectively. If 70% of the population were vaccinated when the alpha variant was dominant (scenario E), the total number of infected cases and deaths would be 608,000 (95% UI: 122,000-743,000) and 2,700 (95% UI: 700-4,000), respectively. The R t was ≥1 almost every day during the epidemic. Our results suggest that policymakers should concentrate on improving vaccination and interventions, such as reducing social contacts, stricter limitations for gathering, public education to promote social distancing, incensing case finding and contact tracing, effective isolation, and quarantine to prevent more COVID-19 cases, hospitalizations, and deaths in Kerman.

Impact of Non-pharmaceutical Interventions on the Control of COVID-19 in Iran: A Mathematical Modeling Study.

BACKGROUND: During the first months of the coronavirus disease 2019 (COVID-19) pandemic, Iran reported high numbers of infections and deaths. In the following months, the burden of this infection decreased significantly, possibly due to the impact of a package of interventions. We modeled the dynamics of COVID-19 infection in Iran to quantify the impacts of these interventions. METHODS: We used a modified susceptible-exposed-infected-recovered (SEIR) model to model the COVID-19 epidemic in Iran, from January 21, 2020 to September 21, 2020. We estimated the 95% uncertainty intervals (UIs) using Markov chain Monte Carlo simulation. Under different scenarios, we assessed the effectiveness of non-pharmaceutical interventions (NPIs) including physical distancing measures and self-isolation. We also estimated the time-varying reproduction number (Rt ), using our mathematical model and epidemiologic data. RESULTS: If no NPIs were applied, there could have been a cumulative number of 51 800 000 (95% UI: 1 910 000- 77 600 000) COVID-19 infections and 266 000 (95% UI: 119 000-476 000) deaths by September 21, 2020. If physical distancing interventions, such as school/border closures and self-isolation interventions had been introduced a week earlier than they were actually launched, 30.8% and 35.2% reduction in the number of deaths and infections respectively could have been achieved by September 21, 2020. The observed daily number of deaths showed that the Rt was one or more than one almost every day during the analysis period. CONCLUSION: Our models suggest that the NPIs implemented in Iran between January 21, 2020 and September 21, 2020 had significant effects on the spread of the COVID-19 epidemic. Our study also showed that the timely implementation of NPIs showed a profound effect on further reductions in the numbers of infections and deaths. This highlights the importance of forecasting and early detection of future waves of infection and of the need for effective preparedness and response capabilities.

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.

Repurposing novel therapeutic candidate drugs for coronavirus disease-19 based on protein-protein interaction network analysis.

BACKGROUND: The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules. RESULTS: Based on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19. CONCLUSIONS: Our computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic.

The Urgency of Conducting Serological Studies for COVID-19.

BACKGROUND: COVID-19 has been the most priority of the world since the early 2020s. We aimed to investigate the importance, urgency and value of serological tests for monitoring and evaluation of COVID-19. STUDY DESIGN: Rapid review. METHODS: This study was conducted through a review of seroepidemiological studies to evaluate their strength and weakness in monitoring and predicting the epidemic situation of COVID-19. RESULTS: Conducting serological studies is an important measure to determine the status of the COVID-19 in affected countries. These studies may also be used to estimate cumulative incidence of the disease, and to get an impression about the level of the epidemic. CONCLUSION: If an accurate serological test is available it can be used for seroepidemiological studies and epidemic investigation in special context, but given the current situation, it may not be possible to be used for screening the normal population and in care and treatment. This research highlighted the importance and urgency of conducting serological studies for monitoring the COVID-19 situation and evaluation of the interventions.

How Can the Epidemic Curve of COVID-19 in Iran Be Interpreted?

BACKGROUND: Iran is one of the countries most affected by COVID-19. This review provides possible interpretations of the observed trend of COVID-19 in Iran. STUDY DESIGN: A rapid review METHODS: We reviewed the daily new cases of COVID-19 based on hospitalized and outpatients, reported deaths, and diagnostic testing in Iran. RESULTS: Iran reported its first peak in the number of cases in late March, 2020. From the 1 April to 3 May 2020, the downward trend in the number of cases was started. The death trend also showed a peak in early April as well as a downward trend in late April. During May, the number of death cases showed a stable trend with a daily number of deaths ranging between 50 and 75 cases. Then the number of deaths gradually increased. CONCLUSION: The epidemic curve in Iran is a function of different factors such number of total tests, change in mitigation policies, and heterogeneities among different provinces in the country. Therefore it should be interpreted under the light of the effect of such factors.

Estimating COVID-19-Related Infections, Deaths, and Hospitalizations in Iran Under Different Physical Distancing and Isolation Scenarios

BACKGROUND: Iran is one of the first few countries that was hit hard with the coronavirus disease 2019 (COVID-19) pandemic. We aimed to estimate the total number of COVID-19 related infections, deaths, and hospitalizations in Iran under different physical distancing and isolation scenarios. METHODS: We developed a susceptible-exposed-infected/infectious-recovered/removed (SEIR) model, parameterized to the COVID-19 pandemic in Iran. We used the model to quantify the magnitude of the outbreak in Iran and assess the effectiveness of isolation and physical distancing under five different scenarios (A: 0% isolation, through E: 40% isolation of all infected cases). We used Monte-Carlo simulation to calculate the 95% uncertainty intervals (UIs). RESULTS: Under scenario A, we estimated 5 196 000 (UI 1 753 000-10 220 000) infections to happen till mid-June with 966 000 (UI 467 800-1 702 000) hospitalizations and 111 000 (UI 53 400-200 000) deaths. Successful implantation of scenario E would reduce the number of infections by 90% (ie, 550 000) and change the epidemic peak from 66 000 on June 9, to 9400 on March 1, 2020. Scenario E also reduces the hospitalizations by 92% (ie, 74 500), and deaths by 93% (ie, 7800). CONCLUSION: With no approved vaccination or therapy available, we found physical distancing and isolation that include public awareness and case-finding and isolation of 40% of infected people could reduce the burden of COVID-19 in Iran by 90% by mid-June.