Background The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique. Methods English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms. Results A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries. Conclusions Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.

ObjectiveTo provide global, regional, and national estimates of target population sizes for coronavirus disease 2019 (covid-19) vaccination to inform country specific immunisation strategies on a global scale.DesignDescriptive study.Setting194 member states of the World Health Organization.PopulationTarget populations for covid-19 vaccination based on country specific characteristics and vaccine objectives (maintaining essential core societal services; reducing severe covid-19; reducing symptomatic infections and stopping virus transmission).Main outcome measureSize of target populations for covid-19 vaccination. Estimates use country specific data on population sizes stratified by occupation, age, risk factors for covid-19 severity, vaccine acceptance, and global vaccine production. These data were derived from a multipronged search of official websites, media sources, and academic journal articles.ResultsTarget population sizes for covid-19 vaccination vary markedly by vaccination goal and geographical region. Differences in demographic structure, presence of underlying conditions, and number of essential workers lead to highly variable estimates of target populations at regional and country levels. In particular, Europe has the highest share of essential workers (63.0 million, 8.9%) and people with underlying conditions (265.9 million, 37.4%); these two categories are essential in maintaining societal functions and reducing severe covid-19, respectively. In contrast, South East Asia has the highest share of healthy adults (777.5 million, 58.9%), a key target for reducing community transmission. Vaccine hesitancy will probably impact future covid-19 vaccination programmes; based on a literature review, 68.4% (95% confidence interval 64.2% to 72.6%) of the global population is willing to receive covid-19 vaccination. Therefore, the adult population willing to be vaccinated is estimated at 3.7 billion (95% confidence interval 3.2 to 4.1 billion).ConclusionsThe distribution of target groups at country and regional levels highlights the importance of designing an equitable and efficient plan for vaccine prioritisation and allocation. Each country should evaluate different strategies and allocation schemes based on local epidemiology, underlying population health, projections of available vaccine doses, and preference for vaccination strategies that favour direct or indirect benefits.

We previously showed that platelet aggregation and thrombus formation occurred in mice lacking both fibrinogen (Fg) and von Willebrand factor (VWF) and that plasma fibronectin (pFn) promoted thrombus growth and stability in injured arterioles in wild-type mice. To examine whether pFn is required for Fg/VWFindependent thrombosis, we generated Fg/VWF/conditional pFn triple-deficient (TKO; Cre ؉ , Fn flox/flox , Fg/VWF ؊/؊ ) mice and littermate control (Cre ؊ , Fn flox/flox , Fg/ VWF ؊/؊ ) mice. Surprisingly, TKO platelet aggregation was not abolished, but instead was enhanced in both heparinized platelet-rich plasma and gel-filtered platelets. This enhancement was diminished when TKO platelets were aggregated in pFn-positive control platelet-poor plasma (PPP), whereas aggregation was enhanced when control platelets were aggregated in pFn-depleted TKO PPP. The TKO platelet aggregation can be completely inhibited by our newly developed mouse anti-mouse ␤ 3 integrin antibodies but was not affected by anti-mouse GPIb␣ antibodies. Enhanced platelet aggregation was also observed when heparinized TKO blood was perfused in collagen-coated perfusion chambers. Using intravital microscopy, we further showed that thrombogenesis in TKO mice was enhanced in both FeCl 3 -injured mesenteric arterioles and laser-injured cremaster arterioles. Our data indicate that pFn is not essential for Fg/VWF-independent thrombosis and that soluble pFn is probably an important inhibitory factor for platelet aggregation. IntroductionPlatelet adhesion and subsequent aggregation at the site of vascular injury are key events required for hemostasis. However, excessive platelet accumulation and thrombus formation may result in myocardial infarction or stroke, the 2 leading causes of morbidity and mortality worldwide. 1,2 It has been shown that fibrinogen (Fg) and von Willebrand factor (VWF) are the 2 key molecules required for platelet adhesion and aggregation. 3 Interestingly, we found that platelet aggregation and thrombus formation still occur in mice lacking Fg or VWF or both, 4,5 suggesting that additional molecule(s) can promote platelet aggregation and thrombus formation.We subsequently found that platelet fibronectin (Fn) content was markedly increased in Fg-deficient mice 4 and a severe hypofibrinogenemic human patient, 6 although no alteration of plasma Fn (pFn) was observed in their Fg-deficient blood. The increase in platelet Fn content was found to be due to enhanced pFn internalization via ␤ 3 integrin. 7 Further experiments with pFn conditional deficient mice and Fn heterozygous mice showed that pFn promoted thrombus growth and stability in injured arterioles. 8,9 These data are consistent with recent in vitro studies that showed that Fn assembly on the platelet surface, 10,11 supported thrombus growth. [12][13][14][15] However, the role of pFn in Fg/VWF-independent platelet aggregation and thrombus formation has not been studied. It was expected that pFn may be required for these processes.To address this question, we generated Fg...