Clinical outcomes, immunogenicity, and safety of BNT162b22 Vaccine in Primary Antibody Deficiency (preprint)

Background: Common variable immunodeficiency (CVID) is characterized by an impaired post-vaccination response, high susceptibility to respiratory tract infections, and a broad spectrum of non-infectious complications. Thus, patients with CVID are at high risk of coronavirus disease 2019 (COVID-19), and vaccination’s role in prevention is questionable. The main aim of this study was to evaluate the clinical outcomes, safety, and dynamics of humoral and T-cell immune responses induced by the mRNA vaccine BNT162b2 in CVID. Methods: This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients, disease severity), safety (adverse-event incidence, laboratory-parameter changes), and dynamics of humoral (specific post-vaccination and virus-neutralizing-antibody assessment) and T-cell immune responses (anti-SARS-CoV-2 specific T-cell detection) in 21 patients with CVID after a two-dose administration of BNT162b2. The patients were followed for 6 months. Results: Humoral response was observed in 52% (11/21) of patients at month 1 post-vaccination but continuously decreased to 33.3% (5/15) at month 6. Nevertheless, they had a remarkably lower anti-SARS-CoV-2 neutralizing antibody titer than healthy controls. The T-cell response was measurable in 33% (6/17) of patients with CVID at month 1, and it persisted for the study period. Mild infection occurred in three patients (14.3%) within the follow-up period. The vaccine also exhibited a favorable safety profile. Conclusions: The BNT162b2 vaccine elicited a measurable antibody response in a high proportion of patients, but it was limited by low titer of the virus-neutralizing antibodies and rapid waning of anti-RBD SARS-CoV-2 specific antibodies. T-cell response was detected in one-third of the patients and remained stable within the follow-up period. Vaccination has favorable safety and clinical-related outcomes in preventing severe COVID-19.

COVID-19 Antigen Testing: Better than We Know? (preprint)

Background: Antigen testing (AGT) for SARS-CoV-2 is generally considered to be less sensitive than the standard reference method – RT-PCR. It has been suggested that a significant part of patients with positive RT-PCR “missed” by AGT might be free of viable virus and, thus, non-infectious. However, to the best of our knowledge, no head-to-head comparison of this has been performed so far.Methods: In a screening setting for asymptomatic or mildly symptomatic patients, 496 patients were tested using RT-PCR as well as a single AGT. Where the results differed, virus viability was evaluated by culture on CV-1 cells. Screening test parameters were calculated with RT-PCR and RT-PCR corrected on viability as reference standards.Findings: The sensitivity of the used AGT related to the RT-PCR only was mere 76·2%. However, 36 out of 39 patients “missed” by AGT contained no viable virus. After correction on that, the sensitivity grew to 97·7% and, more importantly for disease control purposes, the negative predictive value reached 99·2%.Interpretation: We propose that viability testing should be always performed when evaluating a new antigen test. Our results also indicate that a well-chosen and validated antigen test provides excellent results in the identification of patients who are shedding viable virus (although some caveats still remain) in the screening setting of asymptomatic or mildly symptomatic individuals.Funding Statement: This research was internally funded by the Hospital Karvina-Raj and the Public Health Institute Ostrava. Antigen tests were provided by the Ministry of Health of the Czech Republic.Declaration of Interests: All Authors declare that they have no conflict of interest regarding the research presented in this paper.Ethics Approval Statement: The study was approved by the local Ethics Committee, No. NsPKar/19956/2020/SEK.