This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

OBJECTIVE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19).
METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect.
RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness.
CONCLUSIONS: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.

Annual vaccination is widely recommended for influenza and SARS-CoV-2. In this essay, we analyse and question the prevailing policymaking approach to these respiratory virus vaccines, especially in the United States. Every year, licensed influenza vaccines are reformulated to include specific strains expected to dominate in the season ahead. Updated vaccines are rapidly manufactured and approved without further regulatory requirement of clinical data. Novel vaccines (i.e. new products) typically undergo clinical trials, though generally powered for clinically unimportant outcomes (e.g. lab-confirmed infections, regardless of symptomatology or antibody levels). Eventually, the current and future efficacy of influenza and COVID-19 vaccines against hospitalization or death carries considerable uncertainty. The emergence of highly transmissible SARS-CoV-2 variants and waning vaccine-induced immunity led to plummeting vaccine effectiveness, at least against symptomatic infection, and booster doses have since been widely recommended. No further randomized trials were performed for clinically important outcomes for licensed updated boosters. In both cases, annual vaccine effectiveness estimates are generated by observational research, but observational studies are particularly susceptible to confounding and bias. Well-conducted experimental studies, particularly randomized trials, are necessary to address persistent uncertainties about influenza and COVID-19 vaccines. We propose a new research framework which would render results relevant to the current or future respiratory viral seasons. We demonstrate that experimental studies are feasible by adopting a more pragmatic approach and provide strategies on how to do so. When it comes to implementing policies that seriously impact people\'s lives, require substantial public resources and/or rely on widespread public acceptance, high evidence standards are desirable.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined.
METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure.
RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions.
CONCLUSIONS: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

BACKGROUND: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses.
METHODS: Prevaccination and postvaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV.
RESULTS: Among SARS-CoV-2 infection-naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The prevaccination antibody response to the common cold human coronaviruses did not negatively impact the postvaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralization tests.
CONCLUSIONS: Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV.

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BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are among patients with highest risk of adverse coronavirus disease 2019 (COVID-19) outcomes.
OBJECTIVE: We compared clinical outcomes in post-HSCT patients with COVID-19 before and during the Omicron period.
METHODS: This was a retrospective study including patients post-HSCT with severe acute respiratory syndrome coronavirus 2 infection from April 2020 to March 2023 at Instituto Nacional de Cancerología, Mexico City. We describe their clinical characteristics and report the variables associated with severe clinical disease, hospitalization, and death.
RESULTS: Fifty-three patients were included; 31 (58.5%) from the pre-Omicron period and 22 (41.5%) from the Omicron period. Median age was 42-years old (interquartile range 26-53), and 31 patients (59%) were men. Only four patients (16%) had received a vaccine prior to COVID-19 diagnosis in the pre-Omicron period versus 20 (91%) in the Omicron period (p < 0.001). COVID-19 severe cases were more common before Omicron: seven patients (23%) versus two patients (9%). Only one patient (3%) received an antiviral in the pre-Omicron period compared to 11 patients (50%) during the Omicron period (p < 0.01). COVID-19-associated mortality was almost double in the pre-Omicron period (16% vs. 9%, p = 0.6).
CONCLUSIONS: This study reports patients with a high proportion of severe outcomes during the first 2 years of the pandemic. Outcomes improved during Omicron with better access to vaccines and antivirals and no in-hospital cases. Variables associated with worse outcomes were similar to other reports. Strengthening infection control measures in the hospital and better access to preventive strategies and therapeutic options are mandatory in these high-risk patients.

BACKGROUND: SARS-CoV-2, a highly dynamic beta-coronavirus, can afflict all age groups. Notably, over 16100 mortalities have been recorded among children as yet. In this regard, many vaccine projects are operational to assess immuno-potency among young cohorts. A bulk of reports have evidenced the efficacy of these immunization technologies in the elderly population, though the impact is yet to be determined among children.
OBJECTIVE: This review is envisioned to outline the current efficacy of contributing vaccine technologies and examine the dose-dependent impact of immunization regimens in lowering the risks of SARS-CoV-2 infections among children and adolescents. Furthermore, the current review exclusively estimated the vaccine impact at current doses.
METHODS: A total of 52 research papers extracted from PubMed, Pubmed Central, Science Direct, Research Gate, Google Scholar and Semantic Scholar were screened along with an emphasis on patents. Inclusion criteria involved all published reports directly or indirectly linked to the contributing vaccine candidates that are operational among the young cohort. Unrelated research papers were excluded from the study. Key search terminologies included information on vaccine identifiers, such as name, type and clinical trial ID, and successively restricted to children and adolscents age groups.
RESULTS: Several vaccine designs, such as mRNA-based vaccinations, viral vector vaccines, DNA vaccines, inactivated vaccines, recombinant vaccines, and protein-based immunizations, are being examined at various stages of clinical trials to gauge the effects on children and adolescents. With reference to the published reports, the mRNA 1273 (1610 GMT; 6-10 yrs, 1401 GMT; 12-15 yrs), BNT162b2 (1407 GMT; 6 months- <2 yrs, 1535 GMT; 2-4 yrs, 4583 GMT; 5-11 yrs, 1239.5 GMT; 12-15 yrs) and Ad5 nCoV (1037.5 GMT; 6-17 yrs) offered relatively high neutralization titers with sharp seroconversion rates compared to MVC-COV1901 (648.5 GMT; 12-17 yrs) and ZyCoV-D (133.49 GMT; 12-17 yrs), which produced modest immune responses.
CONCLUSIONS: Currently, the WHO is analyzing emerging evidence to issue an emergency use list of vaccines for vaccinating children and adolescents.

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.

BACKGROUND: Reports of intravascular thrombosis and cardiac complications have raised concerns about the safety of COVID-19 vaccinations, particularly in patients with high cardiovascular risk. Herein, we aimed to analyze the impact of preoperative COVID-19 vaccination on outcomes after coronary artery bypass grafting (CABG).
RESULTS: Among 520 patients who underwent isolated CABG from 2020 to 2022, 481 patients (mean±SD age: 67±11 years, 86 women) whose COVID-19 vaccination status could be confirmed were included. A total of 249 patients who had not received any COVID-19 vaccine before CABG (never vaccinated group) and 214 patients who had completed primary vaccination (fully vaccinated group) were subjected to 1:1 propensity score matching, and 156 pairs of patients were matched. There was no significant difference in early mortality between the 2 groups after matching. After matching, overall survival (P=0.930) and major adverse cardiovascular and cerebrovascular event-free survival (P=0.636) did not differ between the 2 groups. One-year graft patency also did not differ significantly between the 2 groups; all patent grafts in 85/104 patients (82%) and 62/73 patients (85%) in the never vaccinated and fully vaccinated groups, respectively (P=0.685). Subgroup analysis showed equivalent overall and major adverse cardiovascular and cerebrovascular event-free survival among AstraZeneca and Pfizer vaccine recipients and between those with ≤30 days versus >30 days from vaccination to CABG.
CONCLUSIONS: Despite the very high cardiovascular risk for patients undergoing CABG, COVID-19 vaccination did not affect major outcomes after CABG. Therefore, there is no reason for patients with coronary artery disease requiring CABG to avoid preoperative COVID-19 vaccination.