Risk factors affecting COVID-19 vaccine effectiveness identified from 290 cross-country observational studies until February 2022: a meta-analysis and meta-regression.

BACKGROUND: Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19. METHODS: A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle-Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression. RESULTS: Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95-96%) for mRNA and from 86% (95% CI, 83-89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82-87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months. CONCLUSIONS: Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.

Antibodies against platelet factor 4 and the risk of cerebral venous sinus thrombosis in patients with vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector-based vaccines against SARS-CoV-2. This syndrome is caused by antibodies against platelet factor 4 (PF4; CXCL4) that lead to platelet activation and is characterized by thrombocytopenia and thrombosis in unusual locations, including cerebral venous sinus thrombosis (CVST). VITT can be classified based on anti-PF4 antibodies properties in vitro: those that require PF4 to activate platelets (PF4-dependent) and those that can activate platelets without additional PF4 (PF4-independent) in the serotonin release assay. OBJECTIVES: We aim to characterize the relationship of VITT platelet-activating profiles with CVST. METHODS: We conducted a retrospective cohort study involving patients with confirmed VITT who were tested between March and June 2021. Data were collected with an anonymized form and cases were identified as VITT with high clinical suspicion according to platelet activation assays. Anti-PF4 antibody binding regions on PF4 were further characterized with alanine scanning mutagenesis. RESULTS: Of the patients with confirmed VITT (n = 39), 17 (43.6%) had PF4-dependent antibodies and 22 (56.4%) had PF4-independent antibodies. CVST occurred almost exclusively in PF4-independent patients (11 of 22 vs 1 of 17; P < .05). Additionally, PF4-independent antibodies bound to 2 distinct epitopes on PF4, the heparin-binding region and a site typical for heparin-induced thrombocytopenia antibodies, whereas PF4-dependent antibodies bound to only the heparin-binding region. CONCLUSION: These findings suggest that VITT antibodies that cause PF4-independent platelet activation represent a unique subset of patients more likely to be associated with CVST, possibly due to the 2 different types of anti-PF4 antibodies.

A Novel Vaccine Strategy to Prevent Cytauxzoonosis in Domestic Cats.

Cytauxzoonosis is caused by Cytauxzoon felis (C. felis), a tick-borne parasite that causes severe disease in domestic cats in the United States. Currently, there is no vaccine to prevent this fatal disease, as traditional vaccine development strategies have been limited by the inability to culture this parasite in vitro. Here, we used a replication-defective human adenoviral vector (AdHu5) to deliver C. felis-specific immunogenic antigens and induce a cell-mediated and humoral immune response in cats. Cats (n = 6 per group) received either the vaccine or placebo in two doses, 4 weeks apart, followed by experimental challenge with C. felis at 5 weeks post-second dose. While the vaccine induced significant cell-mediated and humoral immune responses in immunized cats, it did not ultimately prevent infection with C. felis. However, immunization significantly delayed the onset of clinical signs and reduced febrility during C. felis infection. This AdHu5 vaccine platform shows promising results as a vaccination strategy against cytauxzoonosis.

Short-Term Adverse Effects Following Booster Dose of Inactivated-Virus vs. Adenoviral-Vector COVID-19 Vaccines in Algeria: A Cross-Sectional Study of the General Population.

COVID-19 booster vaccines have been adopted in almost all countries to enhance the immune response and combat the emergence of new variants. Algeria adopted this strategy in November 2021. This study was conducted to consider the self-reported side effects of COVID-19 booster vaccines by Algerians who were vaccinated with a booster dose of one of the approved inactivated-virus vaccines, such as BBIBP-CorV and CoronaVac, or one of the adenoviral-vector-based vaccines, such as Gam-COVID-Vac, AZD1222 and Ad26.COV2.S, and to determine the eventual risk factors. A cross-sectional study using an online self-administered questionnaire (SAQ) was conducted in Algeria between 28 April 2022, and 20 July 2022. A descriptive analysis of the 196 individuals who were included showed a nearly equal distribution of adenoviral- (52%) and inactivated-virus vaccines (48%) and of males (49.5%) and females (50.5%). The results showed that 74.7% of the studied population reported at least one local or systemic side effect. These side effects were more frequent among adenoviral-vector vaccinees (87.3%) than inactivated-virus vaccinees (60.6%) (sig. < 0.001). Injection site pain (40.3%), heat at the injection site (21.4%), and arm pain (16.3%) were the most common local side effects. These signs generally appeared in the first 12 h (73.3%) and generally lasted less than 24 h (32.8%). More interestingly, these signs differed from those that followed the administration of primer doses (48.5%) and were generally more severe (37%). The same observation was reported for systemic side effects, where the signs were especially most severe in the adenoviral-vaccinated group (49.4% vs. 20.8%; sig. = 0.001). These signs generally appeared within the first day (63.6%) and mostly disappeared before two days (50.8%), with fatigue (41.8%), fever (41.3%), and headache (30.1%) being the most common. Adenoviral-vector vaccinees (62.7%) were more likely to use medications to manage these side effects than were inactivated-virus vaccinees (45.7%) (sig. = 0.035) and paracetamol (48.5%) was the most used medication. Adenoviral-based vaccines were the types of vaccines that were most likely to cause side effects. In addition, being female increased the risk of developing side effects; regular medication was associated with local side effects among inactivated-virus vaccinees; and previous infection with COVID-19 was associated with systemic and local side effects among adenovirus-based vaccinees. These results support the short-term safety of booster vaccines, as has been reported for primer doses.

Thrombotic Complications after COVID-19 Vaccination: Diagnosis and Treatment Options.

Coronavirus disease 2019 (COVID-19) vaccines were developed a few months after the emergence of the pandemic. The first cases of vaccine-induced thrombotic complications after the use of adenoviral vector vaccines ChAdOx1 nCoV-19 by AstraZeneca, and Ad26.COV2.S by Johnson & Johnson/Janssen, were announced shortly after the initiation of a global vaccination program. In these cases, the occurrence of thrombotic events at unusual sites-predominantly located in the venous vascular system-in association with concomitant thrombocytopenia were observed. Since this new entity termed vaccine-induced thrombotic thrombocytopenia (VITT) shows similar pathophysiologic mechanisms as heparin-induced thrombocytopenia (HIT), including the presence of antibodies against heparin/platelet factor 4 (PF4), standard routine treatment for thrombotic events-arterial or venous-are not appropriate and may also cause severe harm in affected patients. Thrombotic complications were also rarely documented after vaccination with mRNA vaccines, but a typical VITT phenomenon has, to date, not been established for these vaccines. The aim of this review is to give a concise and feasible overview of diagnostic and therapeutic strategies in COVID-19 vaccine-induced thrombotic complications.