ABSTRACT
Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.
ABSTRACT
Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZenecas ChAdOx1-nCov-19 vaccine. As a consequence, several European governments recommended using this vaccine only in individuals older than 60 years leaving millions of ChAd primed individuals with the decision to either receive a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical Schools COVID-19 Contact (CoCo) Study cohort of health care professionals (HCP) to monitor ChAd primed immune responses before and three weeks after booster with ChAd or BioNTech/Pfizers BNT162b2. Whilst both vaccines boosted prime-induced immunity, BNT induced significantly higher frequencies of Spike-specific CD4 and CD8 T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and the P.1 variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).
ABSTRACT
BackgroundDuring the current pandemic, healthcare professionals (HCP) have been at the frontline of the crisis. Serological screening may help in identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence. However, given the rapidly evolving situation in spring 2020, many questions regarding coronavirus disease 2019 (COVID-19) infection risk and utility of serological testing remained unanswered. To address these questions, we initiated the COVID-19 Contact (CoCo) study at Hannover Medical School, a large university hospital in Northern Germany and affiliated care providers. MethodsThe CoCo study is an ongoing, prospective, longitudinal, observational study in HCP and individuals with potential contact to SARS-CoV-2. It monitors anti-SARS-CoV-2 immunoglobulin serum levels and collects information on symptoms of respiratory infection, work and home environment, and self-perceived SARS-CoV-2 infection risk. Inclusion criteria are (1) working as HCP in clinical care at our university centre, affiliated hospitals or private practices, (2) written informed consent and (3) age >18 years. Exclusion criteria are (1) refusal to give informed consent and (2) contraindication to venepuncture. Study participants are asked to provide weekly to six-monthly samples (7.5 ml serum and 7.5 ml EDTA blood) and fill out a questionnaire. Since March 2020, around 1250 HCP have been included in the study. At each study visit, sera are screened for anti-SARS-CoV-2 spike protein 1 (S1) immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Positive or borderline positive samples are re-assessed with an alternative serological test. Individual results for each study participant are made available online via a dedicated study website. This study also aims to compare different serological testing assays, as well as explore further humoral and cellular immune markers. Study protocols are continually adapted to the rapidly evolving situation of the current pandemic. DiscussionThis ongoing prospective study will aim to answer central questions on the prevalence and kinetics of anti-SARS-CoV-2-humoral immune responses and the validity of serological testing of HCP in a region with high healthcare standard and comparatively low COVID-19 prevalence. As such, our results are highly relevant to other regions and may support HCP around the world in managing this unprecedented situation. Trial registrationGerman Clinical Trial Registry, DRKS00021152. Registered 4th April 2020 -retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021152 Protocol summary O_TBL View this table: org.highwire.dtl.DTLVardef@1066beborg.highwire.dtl.DTLVardef@9734b4org.highwire.dtl.DTLVardef@1052a3dorg.highwire.dtl.DTLVardef@183b87org.highwire.dtl.DTLVardef@ec4318_HPS_FORMAT_FIGEXP M_TBL C_TBL
ABSTRACT
BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2. ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12{middle dot}4 % in week six, p<0.001). In sera of convalescent PCR-confirmed COVID-19 patients, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from ELISAs using e.g. the S1 spike protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralization. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the six week study period. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralization against live SARS CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%. ConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.
ABSTRACT
Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells using surface-expressed angiotensin-converting enzyme 2 (ACE2). We developed a surrogate neutralization test (sVNT) to assess at what degree serum antibodies interfere with the binding of SARS-CoV-2-S-RBD to ACE2. The sVNT revealed neutralizing anti-SARS-CoV-2-S antibodies in the sera of 90% of mildly and 100% of severely affected coronavirus-disease-2019 (COVID-19) convalescent patients. Importantly, sVNT results correlated strongly to the results from pseudotyped-vesicular stomatitis virus-vector-based neutralization assay and to levels of anti-SARS-CoV-2-S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies also correlated to duration and severity of clinical symptoms, but not patient age or gender. These findings together with the sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.
ABSTRACT
There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health care system. The COVID-19 Contact (CoCo) Study follows 217 frontline healthcare professionals at a university hospital with weekly SARS-CoV-2 specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 20.9% (range 0 to 90%). In contrast, anti-SARS-CoV-2-IgG prevalence was about 1-2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.