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.

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.

SARS-CoV-2 Seroprevalence Among Health Care Workers in Major Private and Public Hospitals With COVID-19 Patient's Referral in Tehran, Iran.

Estimating the prevalence of SARS-CoV-2 antibody seropositivity among health care workers (HCWs) is crucial. In this study, the seroprevalence of anti-SARS-CoV-2 antibodies among HCWs of five hospitals of Tehran, Iran with high COVID-19 patient's referrals from April to June, 2020, was assessed. In this cross-sectional study, HCWs from three public and two private hospitals, selected randomly as a pilot, were included. Participants were asked questions on their demographic characteristics, medical history, hospital role, and usage of personal protective equipment (PPE). Iran FDA-approved SARS-CoV-2 ELISA kits were used to detect IgG and IgM antibodies in blood samples. The seroprevalence was estimated on the basis of ELISA test results and adjusted for test performance. Among the 2,065 participants, 1,825 (88.4%) and 240 (11.6%) HCWs were recruited from public and private hospitals, respectively. A total of 340 HCWs were tested positive for SARS-CoV-2-specific IgG or IgM antibodies, and 17.9% of seropositive individuals were asymptomatic. The overall test performance-adjusted seroprevalence estimate among HCWs was 22.6 (95% CI: 20.2-25.1), and PPE usage was significantly higher among HCWs of public vs. private hospitals (66.5 vs. 20.0%). This study found that seroprevalence of SARS-CoV-2 among HCWs was higher in private hospitals (37.0%; 95% CI: 28.6-46.2) than public hospitals (20.7%; 95% CI: 18.2-23.3), and also highest among assistant nurses and nurses, and lowest among janitor or superintendent categories. The PPE usage was especially suboptimal among HCWs in private hospitals. Continued effort in access to adequate PPE and regular screening of hospital staff for detecting asymptomatic personnel, especially during the upcoming wave of infection, are warranted.

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.

Impact of COVID-19-related public health measures on HCV testing in British Columbia, Canada: An interrupted time series analysis.

BACKGROUND & AIMS: Public health measures introduced to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), also disrupted various healthcare services in many regions worldwide, including British Columbia (BC), Canada. We assessed the impact of these measures, first introduced in BC in March 2020, on hepatitis C (HCV) testing and first-time HCV-positive diagnoses within the province. METHODS: De-identified HCV testing data for BC residents were obtained from the provincial Public Health Laboratory. Weekly changes in anti-HCV, HCV RNA and genotype testing episodes and first-time HCV-positive (anti-HCV/RNA/genotype) diagnoses from January 2018 to December 2020 were assessed and associations were determined using segmented regression models examining rates before vs after calendar week 12 of 2020, when measures were introduced. RESULTS: Average weekly HCV testing and first-time HCV-positive diagnosis rates fell immediately following the imposition of public health measures by 62.3 per 100 000 population and 2.9 episodes per 1 000 000 population, respectively (P < .0001 for both), and recovered in subsequent weeks to near pre-March 2020 levels. Average weekly anti-HCV positivity rates decreased steadily pre-restrictions and this trend remained unchanged afterwards. CONCLUSIONS: Reductions in HCV testing and first-time HCV-positive diagnosis rates, key drivers of progression along the HCV care cascade, occurred following the introduction of COVID-19-related public health measures. Further assessment will be required to better understand the full impact of these service disruptions on the HCV care cascade and to inform strategies for the re-engagement of people who may have been lost to care because of these measures.

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

BACKGROUND: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. MATERIAL AND METHODS: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. RESULTS: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 109 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. CONCLUSION: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.

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.