Project description:Recently, the protective and/or pathological role of virus-specific T cells in SARS-CoV-2 infection has been the focus of many studies. We investigated the anti-spike IgG levels and SARS-CoV-2-specific T cells in 125 donors (90 vaccinated with four different vaccine platforms, 16 individuals with a previous natural infection, and 19 not vaccinated donors who did not report previous SARS-CoV-2 infections). Our data show that anti-spike IgG titers were similar between naturally infected subjects and those vaccinated with adenoviral vector vaccines. Of note, all immunized donors produced memory CD4+ and/or CD8+ T cells. A sustained polyfunctionality of SARS-CoV-2-specific T cells in all immunized donors was also demonstrated. Altogether, our data suggest that the natural infection produces an overall response like that induced by vaccination. Therefore, this detailed immunological evaluation may be relevant for other vaccine efforts especially for the monitoring of novel vaccines effective against emerging virus variants.
Project description:Background and purposeDuring the COVID-19 pandemic, myasthenia gravis (MG) patients have been identified as subjects at high risk of developing severe COVID-19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS-CoV-2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS-CoV-2 vaccines were assessed in a large cohort of MG patients from two referral centers.MethodsPatients with confirmed MG diagnosis, consecutively seen between October and December 2021 at two MG centers, were enrolled. Demographics, clinical characteristics, and information regarding SARS-CoV-2 infection/vaccination were extracted from medical reports and/or collected throughout telephonic or in-person interviews.ResultsNinety-eight (94.2%) of 104 patients included were administered at least two vaccine doses 4 weeks before the interview or earlier, and among them, 63 of 98 (64.2%) have already received the "booster" dose. The most frequently used vaccines were BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna. Overall, only minor side effects were reported, most commonly local pain and fever. MG worsening after vaccination was observed in eight of 104 (7.7%) cases. The frequency of worsening among muscle-specific tyrosine kinase MG cases (3/9, 33.3%) was significantly higher compared to other serological subgroups. Spontaneous symptom regression was observed in six of eight cases. Twelve of 104 (11.5%) patients had SARS-CoV-2 infection, and none of the SARS-CoV-2-infected MG patients worsened after vaccination.ConclusionsOur data support the safety and tolerability of mRNA COVID-19 vaccines, which should be strongly recommended in MG patients, who could be at higher risk of complications if exposed to SARS-CoV-2 infection.
Project description:The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL6 inhibition, we sought to evaluate outcomes following COVID-19 and SARS-CoV-2 vaccination in CD patients. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 CD patients enrolled in ACCELERATE, a natural history registry of CD patients. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose one (62/112, 55%) were comparable to the general U.S. population. While there were two cases of CD flares occurring shortly after SARS-CoV-2 infection (N=1) and vaccination (N=1), over 100 patients in this study that were infected and/or vaccinated did not experience CD flares. The median anti-spike titer six months after the second dose among CD patients was comparable to individuals with other immune-related diseases and healthy populations. Data from this small cohort suggest that, despite being on immunosuppressive therapies, CD patients do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered on clinicaltrials.gov (#NCT02817997).
Project description:ImportanceKawasaki disease (KD) symptoms significantly overlap with multisystem inflammatory syndrome in children due to COVID-19. Patients with KD may be at risk for adverse outcomes from exposure to SARS-CoV-2 infection or vaccination.ObjectiveTo describe the outcomes of patients with KD to SARS-CoV-2 infection or vaccination.Design, setting, and participantsThis case series evaluated 2 cohorts using an existing KD database and reviewed individual electronic medical records for the period spanning January 1, 2020, through January 31, 2022, via electronic medical records that include Washington state immunization records. Vaccine cohort inclusion criteria consisted of being 21 years or younger at immunization and receiving 1 or more BNT162b2 (Pfizer-BioNTech) or messenger RNA (mRNA)-1273 (Moderna) vaccine doses. The COVID-19 cohort included patients 21 years or younger with positive polymerase chain reaction or nuclear capsid IgG findings for SARS-CoV-2. Participants included 826 patients from a preexisting KD database. One hundred fifty-three patients received at least 1 BNT162b2 or mRNA-1273 vaccine dose and were included in the mRNA vaccine cohort. Thirty-seven patients had positive test results for SARS-CoV-2 and were included in the COVID-19 cohort.ExposuresSARS-CoV-2 vaccination and/or infection.Main outcomes and measuresAdverse events after mRNA vaccination and/or COVID-19, including clinician visits, emergency department encounters, or hospitalizations.ResultsAmong the 153 patients included in the mRNA vaccination cohort (mean [SD] age, 13.0 [4.3] years; 94 male [61.4%]), the BNT162b2 vaccine was provided for 143 (93.5%), and the remaining 10 (6.5%) received mRNA-1273 or a combination of both. Among patients in the vaccine cohort, 129 (84.3%) were fully vaccinated or received a third-dose booster. No clinically severe adverse events occurred, and there were no reports of vaccine-related hospitalizations or outpatient visits. The COVID-19 cohort included 37 patients (mean [SD] age, 11.0 [5.5] years; 22 male [59.5%]). No patients required hospitalization due to COVID-19. The most common symptoms included low-grade fever, fatigue, cough, and myalgia with resolution within a few days. Two patients, aged 9 and 19 years, had extended cough and fatigue for 3 to 4 weeks. One patient developed COVID-19 within 6 weeks of receiving intravenous immunoglobulin for KD.Conclusions and relevanceThese findings suggest that the mRNA vaccines may be safe and COVID-19 may not be severe for patients with a history of KD.
Project description:BackgroundThe continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects.MethodsBlood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61).ResultsWe report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain.ConclusionsThese results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population.
Project description:We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.
Project description:In vaccinees who were infected with SARS-CoV in 2003, we observed greater antibody responses against spike and nucleoprotein of both SARS-CoV-2 and SARS-CoV after a single dosage of inactivated SARS-CoV-2 vaccine. After receiving the second vaccination, antibodies against RBD of SARS-CoV-2 Wuhan, Beta, Delta, and recently emerged Omicron are significantly higher in SARS-CoV experienced vaccinees than in SARS-CoV naïve vaccinees. Neutralizing activities measured by authentic viruses and pseudoviruses of SARS-CoV, SARS-CoV-2 Wuhan, Beta, and Delta are greater in SARS-CoV experienced vaccinees. In contrast, only weak neutralizing activities against SARS-CoV-2 and variants were detected in SARS-CoV naïve vaccinees. By 6 months after the second vaccination, neutralizing activities were maintained at a relatively higher level in SARS-CoV experienced vaccinees but were undetectable in SARS-CoV naïve vaccinees. These findings suggested a great possibility of developing a universal vaccine by heterologous vaccination using spike antigens from different SARS-related coronaviruses.
Project description:BackgroundThe mobilization and redistribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T-cells and neutralizing antibodies (nAbs) during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019 (COVID-19). We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.MethodsEighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine. All major leukocyte subtypes were enumerated before, during, and after exercise by flow cytometry, and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays, T-cell receptor (TCR)-β sequencing, and SARS-CoV-2 nAb serology.ResultsCOVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise. However, non-infected participants had a significantly reduced mobilization of CD4+ and CD8+ naive T-cells, as well as CD4+ central memory T-cells, after vaccination (synthetic immunity group); this was not seen after vaccination in those with prior SARS-CoV-2 infection (hybrid immunity group). Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner. Both groups mobilized T-cells that reacted to spike protein; however, only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens. nAbs increased significantly during exercise only in the hybrid immunity group.ConclusionThese data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
Project description:BackgroundAs COVID-19 becomes endemic, understanding antibody response and transfer during pregnancy is crucial to inform policy and vaccination schedules. While good immunogenicity has been shown from SARS-CoV-2 vaccines, few data are available demonstrating functional responses in pregnant populations and infants.MethodsA prospective, multi-site observational study was completed across 14 centers in England from April 23, 2020, to December 21, 2022. Demographic, COVID infection and vaccination data were collected. Maternal and cord blood samples were taken at delivery, with maternal and neonatal blood samples taken at 6 weeks for participants who had been infected or vaccinated. Antibody concentrations were measured using antibody-dependent complement deposition, antibody-dependent neutrophil phagocytosis, ACE2 inhibition and Roche and EuroImmun antibody binding assays at the UK Health Security Agency.ResultsMaternal vaccination and infection both produced an antibody response in 100% of mothers and 93.8% and 92.9% of neonates, respectively, which persisted at 6 weeks in 95%. The strongest response was seen in mothers who were both vaccinated and infected. Anti-spike antibody response decreased almost 25-fold from first to third trimester vaccination (P=0.013). Placental transfer of antibodies post-infection showed varied results depending on the assay used, with higher transfer ratios observed in assays measuring Fc-mediated antibody effector functions and IgG-specific responses.ConclusionsMaternal vaccination is associated with good immunogenicity and successful antibody transfer to the neonate, particularly with vaccination in early pregnancy. Further study is needed to determine the mechanism by which the timing of vaccination affects antibody transfer. When measuring placental transfer of antibodies, consideration of the assay to use is essential.