Assessment of long-term adverse events regarding different COVID-19 vaccine regimens within an 18-month follow-up study.

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon.

PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.

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.

Impact of TRIM5α and TRIM22 Genes Expression on the Clinical Course of Coronavirus Disease 2019.

OBJECTIVE: The innate immune response in humans involves a wide variety of factors, including the tripartite motif-containing 5α (TRIM5α) and 22 (TRIM22) as a cluster of genes on chromosome 11 that have exhibited antiviral activity in several viral infections. We analyzed the correlation of the expression of TRIM5α and TRIM22 with the severity of Coronavirus Disease 2019 (COVID-19) in blood samples of 330 patients, divided into two groups of severe and mild disease, versus the healthy individuals who never had contact with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS: The transcription level of TRIM5α and TRIM22 was determined by quantitative real-time polymerase chain reaction (qPCR). The laboratory values were collected from the patients' records. RESULTS: The expression of both genes was significantly lower in the severe group containing the hospitalized patients than in both the mild group and the control group. However, in the mild group, TRIM22 expression was significantly higher (p <0.0001) than in the control group while TRIM5α expression was not significantly different between these two groups. We found a relationship between the cycle threshold (Ct) value of patients and the expression of the aforementioned genes. CONCLUSION: The results of our study indicated that lower Ct values or higher RNA viral load might be associated with the downregulation of TRIM5α and TRIM22 and the severity of COVID-19. Additional studies are needed to confirm the results of this study.

Comparing the expression levels of tripartite motif containing 28 in mild and severe COVID-19 infection.

BACKGROUND: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients. RESULTS: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection. CONCLUSION: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins.

The Dynamic Effective Reproductive Number of COVID-19 during the Epidemic in Iran

Background: We aimed to determine the generation time, the best model for estimating reproduction number (R), and to estimate the basic reproduction number (R0) and effective reproduction number (Rt) for COVID-19 in Iran. Methods: We used the daily incidence cases of COVID-19, hospitalized due to a probable diagnosis of COVID-19 from 19 February 2020 to 17 November 2020 in Iran. Four models, including maximum likelihood (ML), exponential growth (EG), time-dependent (TD), sequential Bayesian (SB) were evaluated. The weekly reproduction number with a 95% confidence interval (CI) was calculated. Results: TD model shows the best fit compared to other models for estimating reproduction number in Iran. The R0 in Iran in the first week of the epidemic, leading up to 21 February 2020 was 7.19, 95% CI: 5.56, 9.00. The lowest value for the Rt was equal to 0.77 between 3 to 10 March 2020 and 4 to 11 December 2020. From 11 June 2020 up to13 August 2020, the Rt was more than one but after then to 24 September 2021 was less than one. Conclusion: TD model was the best fit for estimating the R in Iran. The worst situation of the epidemic in Iran was related to the weeks leading up to 26 February 2020 and 28 October 2020, and better status was related to the weeks leading up to 10 March 2020 and 11 December 2020.

Exploration of the Impact of Coronavirus Disease 2019 on People Living With HIV in Kerman, Iran: A Qualitative Study.

ABSTRACT: We explored the impact of the coronavirus disease 2019 (COVID-19) pandemic on people living with HIV (PLWH) in Kerman, Iran. A convenience sample of 18 PLWH from a voluntary counseling and testing (VCT) center (August-October 2020) were invited to participate in face-to-face interviews. Inductive content analysis was performed with MAXQDA software. Six themes were identified: COVID-19-related knowledge and preventive practices, misconceptions about COVID-19, fear of seeking health care services, psychosocial effects, limited or inconvenient access to health care services, and the impact of COVID-19 on socioeconomic status. Although participants generally understood COVID-19 preventative measures, some held misconceptions. COVID-19 negatively affected PLWHs' mental health, financial stability, and use of and access to health care services. Our findings support expansion of services related to HIV care/treatment and mental health to promote health and well-being during the COVID-19 pandemic.

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.

Iran COVID-19 Epidemiology Committee: A Review of Missions, Structures, Achievements, and Challenges.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic in Iran, the control and management of the epidemic were headed by the National Headquarter for the Control of COVID-19 Epidemic through setting up different scientific committees, including the COVID-19 National Epidemiology Committee. The present study reviews the missions, structures, achievements, and challenges of the Epidemiology Committee. STUDY DESIGN: A rapid review . METHODS: All relevant reports, documents, guidelines, published literature, and surveillance data related to the establishment, visions, missions, roles, activities, and outputs of the COVID-19 Epidemiology Committee were critically reviewed in this study. RESULTS: The efforts of the committee's working groups may have impacted improvements in data registration/usage, provincial data quality at provincial levels, and perception of the epidemic situation in the provinces. The committees have also played role in informing the policies in different stages of the epidemic through routine or problem-based data/evidence analyses, epidemic investigations, and mathematical modeling. CONCLUSION: The structure and experience gained by the committee can be used in similar situations within and outside the country. To further improve the impacts of our activities, it is essential to have effective interaction, collaboration, and data flow between the committee and a broad range of organizations within and outside the Ministry of Health and Medical Education.

Adherence to Self-isolation measures by older adults during coronavirus disease 2019 (COVID-19) epidemic: A phone survey in Iran.

Background: Older adults are at higher risk for severe illness and death associated with coronavirus disease 2019 (COVID-19). As Iran was affected by COVID-19 pandemic, the elderly population soon were told to self-isolate for a very long time. We aimed to identify the coverage, efficacy, and integrity of self-isolation and its predictors in the Iranian older adults (≥60 years) from February 19 to 19 March 2020. Methods: Quota sampling was performed to recruit respondents from 16 cities that were selected based on their population size (4, 7, and 5 cities for localities with ≤500 000, 500 000-1 000 000, and ≥1 000 000 populations) and geographical direction (West = 4 cities; North, East, South, Center = 3 each). At least 30 respondents per locality were selected. Phone interviews of 558 respondents (out of 560; response rate = 99.6%) were performed by local trained interviewers using a validated interview form. Association between age, sex, and living condition (with family vs alone) was assessed with Pearson Chi Square and logistic regression analyses. Results: Complete self-isolation was reported by 61% of the respondents. In 72%, self-isolation led to 80%-100% contact reduction. Self-isolation was broken by 26% of the respondents. Females had better self-isolation behaviors (OR adjusted: 2.3, 95% CI: 1.5, 3.3) and higher contact reduction rates (p: 0.067). They kept the integrity of self-isolation better (OR adjusted: 1.8; 95% CI: 1.2, 2.7). Those aged older than 80 years were 2.3-folds more likely to completely self-isolate than younger elderly (95% CI adjusted: 1.2, 4.3). Living alone did not significantly predict self-isolation features in the elderly. Conclusion: About one third of the interviewed Iranian older adults did not adhere to important self-isolation measures, with males and younger ages showing lower adherence. With the relaxation of social distancing measures, protection measures of the elderly should be strengthened. Given that prolonged self-isolation adversely affects physical and mental health status of the elderly, it is highly recommended to think of creative and gender-specific methods that best tailor the needs of this population in Iran.

Association of cigarette smoking, obesity, and underlying medical conditions with COVID-19 hospitalization and mortality in Iran: A nationwide retrospective ecological study.

Background: Coronavirus Disease 2019 (COVID-19) has resulted in a considerable number of deaths worldwide. This ecological study aimed to explore the relationship between COVID-19 hospitalization and mortality with smoking, obesity, and underlying conditions in Iran. Methods: Provincial-level COVID-19 data were obtained from the official reports. Two outcomes were assessed: the total number of hospitalizations and deaths. Data on underlying health conditions, cigarette smoking, and obesity were obtained from national surveys. Negative binomial regression was used to report incident rate (IRR) ratios. Results: As of April 22, 2020, a total number of 43 950 lab-confirmed COVID-19 hospitalizations and 5391confirmed COVID-19 deaths were officially reported. Adjusting for underdetection to cover the number of clinically-confirmed COVID-19 cases, a total of 76 962 additional hospitalizations (ie, total lab- and clinically-confirmed hospitalizations = 120 912; 175% increase) and 7558 additional deaths (ie, total lab- and clinically-confirmed deaths = 12 949; 140% increase) were estimated during the same period. Provinces with a higher prevalence of obesity (IRR: 2.75, 95% CI: 1.49, 5.10), cigarette smoking (1.81; 95% CI: 1.01, 3.27), hypertension (1.88; 95% CI: 1.03, 3.44), and diabetes mellitus (1.74; 95% CI: 0.96, 3.16) had a higher likelihood of COVID-19 death rates. Conclusion: Inequality in COVID-19 hospitalization and mortality was observed in provinces whose populations had underlying diseases, in particular, obesity, cigarette smoking, hypertension, and diabetes.

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.