Differences in clinical outcomes of COVID-19 among vaccinated and unvaccinated kidney transplant recipients

IntroductionThe remarkable efficacy and effectiveness of COVID-19 vaccines have been described in healthy individuals, but kidney transplant recipients have been excluded from these studies. Therefore, real-world evidence of these vaccines can guide clinicians in predicting complications in kidney transplant recipients and how many doses of vaccines are protective. In this study, we aimed to investigate the impact of the COVID-19 vaccines on kidney transplant recipients with SARS-CoV-2 infection.Material and methodThis matched case-control study included vaccinated kidney transplant recipients with COVID-19 from two centers between 1 May and 1 October 2021. All patients in the vaccinated group received a minimum of two doses of the vaccine and were diagnosed with COVID-19 at least one month after the last dose. Each vaccinated patient was matched with an unvaccinated kidney transplant recipient diagnosed with COVID. The endpoints were all-cause mortality, hospitalization, intensive care unit admission, acute kidney injury, cytokine storm, and acute respiratory distress syndrome.ResultsThe median age of vaccinated seventy-two participants was 45 years, and 41 of the participants were men in the vaccinated group. Four patients in the vaccinated group and nine patients in the control group died during follow-up (p = 0.247). Seventeen patients in the vaccinated group, thirty-four participants in the control group were hospitalized (p = 0.004); five vaccinated patients and ten unvaccinated patients were followed-up in the ICU during follow-up (p = 0.168). Thirteen of the vaccinated and twelve unvaccinated patients developed acute kidney injury (p = 0.16). The occurrence of cytokine storm (n = 4 vs. n = 11; p = 0.061) and acute respiratory distress syndrome (n = 5 vs. n = 10; p = 0.168) was higher in the patient group compared to the control group.ConclusionCOVID-19 remains a fatal disease despite advancing treatment modalities and preventive strategies. COVID-19 vaccines can't prevent death in all kidney transplant recipients, but they decrease hospitalization rate and duration in most patients.     

Second dose of the BNT162b2 mRNA vaccine: Value of timely administration but questionable necessity among the seropositive

This study monitored titers of neutralizing IgG against the receptor-binding domain of the SARS-CoV-2 S1 subunit 14 days post-injection of each dose of the BNT162b2 mRNA Covid-19 vaccine in 401 Greek healthcare workers aged 20–67. After the first dose, titers varied upon age and history of infection, being lower in the 50+ age group and significantly higher among the seropositive. After the second dose, immunogenicity was significantly boosted in the age 50+ and SARS-CoV-2-naïve individuals, indicating the effectuality of its timely administration, yet questioning its value among the seropositive.     

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults

BackgroundRisk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0–7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs.MethodsWe conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0–7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories.ResultsFollow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0–7 following dose 2 was not common among case-patients or controls.ConclusionsHistory of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.     

Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

SARS-CoV-2 vaccine breakthrough infections in Virginia,January 17, 2021 – June 30, 2021

As COVID-19 vaccines moved from the controlled environment of clinical trials to use in real-world settings, it has been important to evaluate vaccine effectiveness. A retrospective cohort study was designed to identify cases of SARS-CoV-2 infection that occurred between January 17-June 30, 2021 in fully vaccinated Virginia residents. Of the fully vaccinated population of Virginia at the end of the study period (N = 4,271,505), 2445 (0.057 %) were reported to have experienced a vaccine breakthrough infection. Of those, 183 (7.5 %) were reported to have been hospitalized for COVID-19 and 53 (2.2 %) died from COVID-19. There were significant differences in vaccine effectiveness over time between both mRNA vaccines and the Janssen vaccine. Increasing age, pre-existing medical conditions, and male sex were associated with severe outcomes (hospitalization or death). Persons at greater risk for severe outcomes should continue to take precautions to prevent SARS-CoV-2 infection, even if fully vaccinated.     

Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine

BackgroundThe antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection.MethodsThis prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination.ResultsA total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic.ConclusionsBoth humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent.UMIN Clinical Trials Registry IDUMIN000043340.     

Sub-cutaneous Pfizer/BioNTech COVID-19 vaccine administration results in seroconversion among young adults

Route of vaccine administration plays a role in extent and quality of immunogenicity. 790 military personnel accidentally received the first of two doses of Pfizer/BioNTech mRNA anti Covid-19 vaccine using a needle intended for subcutaneous administration. A serological blood test (on day 21, prior to the second intramuscular dose) was performed, analyzing whether immunological response was elicited. 98.2% demonstrated seroconversion. IgG titers were negatively correlated with age and did not correlate with BMI. Our results could help reassure providers confronted with a similar mistake and may even imply a possibly new and effective administration route.     

COVID-19 impact and vaccine effectiveness among healthcare workers of a large University Hospital in Lombardy,Italy

Background:Healthcare Workers (HCWs) are a key element in managing the COVID-19 pandemic, but they are also at high risk of infection.Objective:The aim of this study was to describe, in a large university hospital which provided healthcare services to patients with SARS-CoV-2 infection, the course of the epidemic among HCWs and effectiveness of COVID-19 vaccination in reducing SARS-CoV-2 infection and disease.Methods:Our case series included all “Fatebenefratelli Sacco” University Hospital workers. Data were collected until the 15th of May 2021 and analysed as part of the health surveillance program carried out by the Occupational Health Unit.Results:From March 2020 until May 2021, 14.4% of workers contracted COVID-19, with the highest incidence peak recorded during the second wave of the pandemic. The prevalence of infection was slightly higher in males than in females, and a greater number of cases was found in job categories characterized by direct patient care activities. We reported a higher prevalence of “serious/critical illness” in elder workers. A clear reduction of COVID-19 incidence was found in our population during the third pandemic wave, that coincided with the start of vaccination campaign.Discussion:HCWs have been at high risk of COVID-19 infection. Male sex and advanced age appear to be predisposing factor and negative prognostic factor respectively. An out-of-hospital setting appears to be the main source of COVID-19 confirming that the correct use of protective devices during work counters the risk of infection. Vaccination seems to reduce both documented cases of infection and severe illness.     

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

BackgroundAlthough several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays.MethodsThis prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20–64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays.ResultsAmong the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively.ConclusionsTwo BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.     

Immunological features that associate with the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

Predictive clinical factors associated with favorable responses to BNT162b2 mRNA vaccine against SARS-CoV-2 have been reported in some studies; however, there is a subgroup with low antibody titers without well-known clinical factors reducing antibody responses. To clarify the immunological backgrounds that underlie the difference in antibody responses, we analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1774 healthcare workers who received BNT162b2 mRNA vaccine. A higher percentage of B cells before vaccination was associated with a higher antibody titer. Among B cells, naïve and transitional B cell frequencies were positively correlated with a higher antibody titer, whereas the frequencies of late memory B cells and plasmablasts were associated with a lower antibody titer. Fold change in the frequency of activated CD8⁺ T cells upon vaccination was also correlated with high antibody titers.     

Cellular and humoral immune responses after a third dose of SARS-CoV-2 mRNA vaccine in lung transplant recipients in Japan

BackgroundLung transplant (LTx) recipients are at higher risk of infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). There is an increasing demand for additional analysis regarding the efficacy and safety of after the initial series of mRNA SARS-CoV-2 vaccines in Japanese transplant recipients.MethodIn this open-label, nonrandomized prospective study carried out at Tohoku University Hospital, Sendai, Japan, LTx recipients and controls received third doses of either the BNT162b2 or the mRNA-1273 vaccine, and the cellular and humoral immune responses were analyzed.ResultsA cohort of 39 LTx recipients and 38 controls participated in the study. The third dose of SARS-CoV-2 vaccine promoted much greater humoral responses at 53.9 % of LTx recipients than after the initial series at 28.2 % of patients without increasing the risk of adverse events. However, still fewer LTx recipients responded to the SARS-CoV-2 spike protein with the median IgG titer of 129.8 AU/mL and with the median IFN-γ level of 0.01 IU/mL when compared to controls with those of 7394 AU/mL and 0.70 IU/mL, respectively.ConclusionAlthough the third dose of mRNA vaccine in LTx recipients was effective and safe, impaired cellular and humoral responses to SARS-CoV-2 spike protein were noted. Given lower antibody production and establishing vaccine safety, repeating the administration of mRNA vaccine will lead to robust protection in such a high-risk population (jRCT1021210009).     

COVID-19 mRNA vaccines as hypothetical epigenetic players: Results from an in silico analysis,considerations and perspectives

ObjectivesTo investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2).MethodsThe publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases.ResultsThe BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions.In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene.ConclusionThis pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.     

新型冠状病毒疫苗对新型冠状病毒德尔塔变异株预防效果的Meta分析

目的 运用循证医学Meta分析方法,探究和评价新型冠状病毒疫苗对新型冠状病毒德尔塔变异株的预防效果,为新冠肺炎的防控提供循证支持。方法 以新型冠状病毒德尔塔毒株、疫苗及其同义词、近义词作为检索词,系统检索中国知网、万方数据库、维普数据库、中国生物医学文献服务系统、PubMed、考科蓝图书馆、Web of Science、BioRxiv、MedRxiv和Europe PMC关于新型冠状病毒疫苗保护效果(Vaccine Effectiveness,VE)的文献,使用纽卡斯尔-渥太华风险评分量表对纳入的队列研究和病例对照研究文献进行质量评价,对纳入的随机对照试验则使用Jadad评分进行质量评价,运用Stata 12.0进行异质性检验、总效应值和发表性偏倚估计。结果 共纳入文献14篇,其中病例对照研究文献5篇,队列研究文献8篇,随机对照实验1篇。Meta分析显示,接种一剂新冠疫苗的合并VE(95%CI)为34.57%(95%CI:21.70%～47.44%),接种两剂新型冠状病毒疫苗的合并VE(95%CI)为70.56%(95%CI: 64.29%～76.82%)。漏斗图分析表明存在发表偏倚风险。结论 接种新型冠状病毒疫苗对预防新型冠状病毒德尔塔变异株有保护作用,且2剂疫苗保护作用明显比1剂疫苗强。后续仍需要收集更多的疫苗保护率研究,提供发表性偏倚风险小的证据。     

Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose.UMIN Clinical Trials Registry ID: UMIN000043340.     

Safety and efficacy of COVID-19 prime-boost vaccinations: Homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals

BackgroundBooster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied.MethodsWe conducted a non-randomized, non-blinded phase II observational community trial across Bahrain, investigating the reactogenic and immunogenic response of participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological status was determined at baseline and on the following 8th week. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling.Results305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study, with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred.ConclusionHeterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated.Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.     

Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice

As the COVID-19 pandemic transitions into endemicity, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD-specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS-CoV-2.     

广州市一起由新型冠状病毒Delta变异株引起的家庭聚集性疫情流行病学调查

目的  分析广州市一起由Delta变异株(B.1.617.2)引起的COVID-19家庭聚集性疫情的流行病学特征,为相关疫情防控提供参考。方法  从中国疾病预防控制中心传染病报告管理信息系统和流行病学调查资料获取病例信息,采用描述性流行病学方法对该起疫情的调查和特征进行分析描述。结果  该起家庭聚集性疫情涉及6名确诊病例,其中男、女各3人,中位年龄为24.50岁,均无新型冠状病毒(简称新冠)疫苗接种史。病例1~4与确诊病例在某餐厅有同时段用餐史,在暴露后4~7 d陆续发病;家庭成员病例5、6则分别在病例1~4发病后2~5 d发病。除病例1、2是由社区集中核酸检测发现,其余4人均是作为病例1、2的密切接触者在集中隔离观察中检测发现。6名病例活动轨迹累计涉及24个重点场所,共甄别密切接触者427人,除病例3~6外无续发感染。结论  结合疫苗接种和非药物类控制措施,重点关注和控制家庭聚集性发病,仍是阻断COVID-19疫情社区传播的重要策略。     

上海某方舱医院新型冠状病毒 奥密克戎变异株感染者流行病学特征分析

[摘要]　目的　探讨上海某方舱医院新型冠状病毒奥密克戎变异株感染者的发病情况及流行病学特征。方法　以2022年4月9日—5月5日上海国家会展中心方舱医院收治的新型冠状病毒奥密克戎变异株感染者为研究对象,对感染者年龄、性别、地区、疫苗接种等疫情数据进行流行病学特征分析。结果　122 151例新型冠状病毒感染者均为奥密克戎变异株BA.2或BA.2.2亚型感染,其流行病学特征结果显示：患者男女比例为1.51:1;平均年龄为（44.91±15.38）岁;0～17岁、18～30岁、31～60岁和≥61岁感染者分别占4.74%、20.80%、62.52%和11.94%;无症状感染者占80.80%,轻型患者占19.20%;平均住院时间为（7.00±2.77）d;未接种和完成1、2和3次疫苗接种的感染者分别占20.30%、3.18%、31.30%和45.22%,其中≥61岁且完成3次疫苗接种的感染者仅占10.10%。结论　各个年龄段人群对于新型冠状病毒奥密克戎变异株普遍易感。无症状感染者是本次疫情的主体人群,临床症状不典型,早期隐匿传播,积极加强核酸检测是早期发现疫情的必要手段。