Effectiveness and Cost-Effectiveness of Inactivated Vaccine to Address COVID-19 Pandemic in China: Evidence From Randomized Control Trials and Real-World Studies.

Objective: This study aimed to determine the efficacy, effectiveness, and cost-effectiveness of inactivated COVID-19 vaccines (CoronaVac and BBIBP-CorV) in China using existing international clinical trials and real-world evidence. Methods: Through a search of PubMed, Embase, Web of Science, and CNKI, studies investigating the effectiveness of inactivated COVID-19 vaccines were identified, and a meta-analysis was undertaken to synthesize the vaccine efficacy and effectiveness data. Moreover, a decision-analytic model was developed to estimate the cost-effectiveness of inactivated vaccines for combating the COVID-19 pandemic in the Chinese context from a societal perspective. Results of the meta-analysis, along with cost data from official websites and works of literature were used to populate the model. Sensitivity analysis was performed to test the robustness of the model results. Results: A total of 24 studies were included in the meta-analysis. In comparison to no immunization, the effectiveness of inactivated vaccine against COVID-19 infection, hospitalization, ICU admission and death were 65.18% (95% CI 62.62, 67.75), 79.10% (95% CI 71.69, 86.51), 90.46% (95% CI 89.42, 91.50), and 86.69% (95% CI 85.68, 87.70); and the efficacy against COVID-19 infection and hospitalization were 70.56% (95% CI 57.87, 83.24) and 100% (95% CI 61.72, 100). Inactivated vaccine vaccination prevented more infections, hospitalizations, ICU admissions, and deaths with lower total costs, thus was cost-saving from a societal perspective in China. Base-case analysis results were robust in the one-way sensitivity analysis, and the percentage of ICU admission or death and direct medical cost ranked the top influential factors in our models. In the probabilistic sensitivity analysis, vaccination had a 100% probability of being cost-effective. Conclusion: Inactivated vaccine is effective in preventing COVID-19 infection, hospitalization, ICU admission and avoiding COVID-19 related death, and COVID-19 vaccination program is cost-saving from societal perspective in China.

Real-World Evidence for COVID-19 Delta Variant's Effects on the Digestive System and Protection of Inactivated Vaccines from a Medical Center in Yangzhou, China: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement.

BACKGROUND: We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. CASE PRESENTATION: A 29-year-old woman recently immunized with inactivated viral vaccine-BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. CONCLUSIONS: ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood-brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

Adverse effects following COVID-19 vaccination in Iran.

BACKGROUND: Vaccination is a key intervention to prevent COVID-19. Many vaccines are administered globally, yet there is not much evidence regarding their safety and adverse effects. Iran also faces this challenge, especially as data regarding the Sputnik V vaccine is sparse. Therefore, the aim of this study is to determine the adverse effects of the most commonly used vaccines in Iran. METHODS: Using a retrospective cohort study design, 6600 subjects aged 18 years or older who had received two doses of any of the three COVID-19 vaccines (Sinopharm, AstraZeneca, and Sputnik V) were selected using a random sampling method between March and August 2021. Subjects were asked about any adverse effects of the vaccines by trained interviewers via telephone interview. Vaccine-related adverse effects in individuals during the first 72 h and subsequently following both doses of the vaccines were determined. The demographic variables, type of administered vaccine, adverse effects, and history of the previous infection with COVID-19 were collected. Descriptive statistics (mean, standard deviation) and analytical statistics (Chi-squared and Wilcoxon tests) were performed at a 95% significance level using STATA software version 15 (STATA Corp, College Station, TX, USA). RESULTS: From 6600 participants, 4775 responded (response rate = 72.3%). Of the participants, 1460 (30.6%) received the AstraZeneca vaccine, 1564 (32.8%) received the Sinopharm vaccine and 1751 (36.7%) received the Sputnik V vaccine. 2653 participants (55.56%) reported adverse effects after the first dose and 1704 (35.7%) after the second dose. Sputnik V caused the most adverse effects with 1449 (82.7%) vaccine recipients reporting symptoms after the first or second dose, compared with 1030 (70.5%) for AstraZeneca and only 585 (37.4%) for the Sinopharm vaccine. The most common adverse effects after the first dose were fatigue (28.37%), chill/fever (26.86%), and skeletal pain (22.38%). These three adverse effects were the same for the second dose, although their prevalence was lower. CONCLUSIONS: In this study, we demonstrate that the Sputnik V vaccine has the highest rate of adverse effects, followed by the AstraZeneca and Sinopharm vaccines. COVID-19 vaccines used in Iran are safe and there were no reports of serious adverse effects.

Effectiveness of inactivated SARS-CoV-2 vaccine (CoronaVac) on intensive care unit survival.

This study compared the course of coronavirus disease 2019 (COVID-19) in vaccinated and unvaccinated patients admitted to an intensive care unit (ICU) and evaluated the effect of vaccination with CoronaVac on admission to ICU. Patients admitted to ICU due to COVID-19 between 1 April 2021 and 15 May 2021 were enrolled to the study. Clinical, laboratory, radiological parameters, hospital and ICU mortality were compared between vaccinated patients and eligible but unvaccinated patients. Patients over 65 years old were the target population of the study due to the national vaccination schedule. Data from 90 patients were evaluated. Of these, 36 (40.0%) were vaccinated. All patients had the CoronaVac vaccine. Lactate dehydrogenase and ferritin levels were higher in an unvaccinated group than vaccinated group (P = 0.021 and 0.008, respectively). SpO2 from the first arterial blood gas at ICU was 83.71 ± 19.50% in vaccinated, 92.36 ± 6.59% in unvaccinated patients (P = 0.003). Length of ICU and hospital stay were not different (P = 0.204, 0.092, respectively). ICU and hospital mortality were similar between groups (P = 0.11 and 0.70, respectively). CoronaVac vaccine had no effect on survival from COVID-19. CoronaVac's protective effect, especially on new genetic variants, should be investigated further.

Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.

Background: Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. Results: In total, 47,086 LT4 users were identified (BNT162b2: n = 12,310; CoronaVac: n = 11,353; and unvaccinated: n = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. Conclusions: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.

Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study.

Anti-COVID-19 vaccination may have functional implications for immune checkpoint inhibitor treatment in patients with cancer. This study was undertaken to determine whether the safety or efficacy of anti-PD-1 therapy is reduced in patients with cancer during COVID-19 vaccination. A large multicenter observational study was conducted in 83 Chinese hospitals between January 28, 2021 and September 30, 2021. A total of 3552 patients were screened and 2048 eligible patients with cancer receiving PD-1 inhibitor treatment were recruited. All enrolled patients had received camrelizumab treatment alone or in conjunction with other cancer therapies. Among these, 1518 (74.1%) patients received the BBIBP-CorV vaccine and were defined as the vaccinated subgroup. The remaining 530 (25.9%) patients did not receive anti-COVID-19 vaccination and were defined as the non-vaccinated subgroup. For all participants, Response Evaluation Criteria in Solid Tumor and Common Terminology Criteria for Adverse Events criteria were used to evaluate the efficacy and safety of camrelizumab treatment, respectively. Propensity score match analysis with the optimal pair matching was used to compare these criteria between the vaccinated and non-vaccinated subgroups. A total of 2048 eligible patients with cancer were included (median age 59 years, 27.6% female). Most patients (98.8%) had metastatic cancer of the lung, liver or intestinal tract. Aside from the PD-1 inhibitor treatment, 55.9% of patients received additional cancer therapies. 1518 (74.1%) patients received the BBIBP-CorV vaccine with only mild side effects reported. The remaining patients did not receive COVID-19 vaccination and had a statistically greater percentage of comorbidities. After matching for age, gender, cancer stage/types, comorbidity and performance status, 1060 patients (530 pairs) were selected for propensity score match analysis. This analysis showed no significant differences in overall response rate (25.3% vs 28.9%, p=0.213) and disease control rate (64.6% vs 67.0%, p=0.437) between vaccinated and non-vaccinated subgroups. Immune-related adverse events (irAEs) were reported in both subgroups after camrelizumab treatment. Among vaccinated patients who experienced irAEs, the median interval between the first dose of camrelizumab treatment and the first vaccine shot was ≤16 days. Compared with the non-vaccinated subgroup, irAEs in vaccinated patients were more frequently reported as mild (grade 1 or 2 irAEs; 33.8% vs 19.8%, p<0.001) and these patients were less likely to discontinue the PD-1 inhibitor treatment (4.2% vs 20.4%, p<0.001). Severe irAEs (grade 3 irAE or higher) related to camrelizumab treatment were reported, however no significant differences in the frequency of such events were observed between the vaccinated and non-vaccinated subgroups. The COVID-19 vaccine, BBIBP-CorV, did not increase severe anti-PD-1-related adverse events nor did it reduce the clinical efficacy of camrelizumab in patients with cancer. Thus, we conclude that patients with cancer need not suspend anti-PD-1 treatment during COVID-19 vaccination.

Comparison of SARS-CoV-2 antibody response after two doses of mRNA and inactivated vaccines in multiple sclerosis patients treated with disease-modifying therapies.

BACKGROUND: Disease-modifying therapy could weaken the immune system and decrease the immune response to vaccines. It is essential to know which vaccine is more protective against SARS-CoV-2 in the multiple sclerosis population. OBJECTIVE: To assess immune response after messenger RNA BNT162b2 (Pfizer/BioNTech) and inactivated Sinovac vaccines in people with multiple sclerosis (pwMS) treated with a disease-modifying therapy (DMT) compared to healthy controls. METHODS: This single-center cross-sectional study included 526 MS patients treated with DMT, 44 healthy controls, and 21 untreated patients with MS between May 2021 and September 2021. Serum samples were collected at least two weeks after the second dose of the vaccine. RESULTS: Participants vaccinated with BNT162b2 had a higher antibody titer than the Sinovac group (95%CI=1.023 - 1.473; p< .001). No significant difference between antibody titer of pwMS without treatment and HC was found [95%CI= -0.882; - 0.935 p > .99]. In 65 adults without DMT use (HC+pwMSwithout treatment), no seronegative cases were observed in any vaccine group. In patients treated with DMT, BNT162b2 was associated with a 16.3% greater absolute risk of seropositivity than Sinovac. CONCLUSION: The mRNA vaccine could be a preferred choice of protection against SARS-CoV-2 in pMS treated with DMT.

Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19), and the resulting pandemic has caused widespread health problems and social and economic disruption. Thus far in 2021, more than 4 million people worldwide have died from COVID-19, so safe and efficacious vaccines are urgently needed to restore normal economic and social activities. According to the official guidance documents of the World Health Organization (WHO), vaccines based on four major strategies including mRNA, adenoviral vectors, inactivated viruses, and recombinant proteins have entered the stage of emergency use authorization and pre-certification evaluation. The current review summarizes these vaccines and it looks ahead to the development of additional COVID-19 vaccines in the future.

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

Does COVID-19 Vaccination Warrant the Classical Principle "ofelein i mi vlaptin"?

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.

Doctor-Should I get the COVID-19 vaccine? Infection and immunization in individuals with neuromuscular disorders.

The clinical course of neuromuscular disorders (NMDs) can be affected by infections, both in immunocompetent individuals, and in those with reduced immunocompetence due to immunosuppressive/immunomodulating therapies. Infections and immunizations may also trigger NMDs. There is a potential for reduced efficacy of immunizations in patients with reduced immunocompetence. The recent vaccination program for coronavirus disease-2019 (COVID-19) raises several questions regarding the safety and efficacy of this vaccine in individuals with NMDs. In this Practice Topic article, we address the role of vaccine-preventable infections in NMDs and the safety and efficacy of immunization in individuals with NMDs, with emphasis on vaccination against COVID-19.

Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.