Jaroslav Janošek

Introduction: Healthy Vaccinee Effect (HVE), arising when generally healthier or more health-conscious individuals are vaccinated, is a major confounder in observational studies on vaccine effectiveness. In principle, we can distinguish between the short-term HVE arising primarily by the fact that individuals who are virtually on their deathbeds are less likely to get vaccinated and the long-term component caused (among other things) by more health-conscious behavior of those opting for vaccination. Methods: In this simulation study, we constructed a model of all-cause mortality in a population vaccinated with a zero-effect (placebo) vaccine. Subsequently, we introduced the short-term HVE with two parameters (HVE magnitude and duration) and assessed the dependence of the observed mortality and apparent vaccine effectiveness patterns on these two parameters. Subsequently, we used real-world population-wide data on all-cause mortality during the COVID-19 pandemic from the Czech Republic to find out if the patterns produced by the model are consistent with the real-world data. Results and discussion: The simulation demonstrated that if vaccination status (not time from vaccination) is used for calculation of vaccine effectiveness, even the short-term component of HVE is capable of creating the illusion of transient apparent vaccine effectiveness for a zero-effect vaccine. We confirm the same pattern in real-world data. Further, we propose a simple method of estimating the magnitude and duration of the short-term component of HVE from real-world data on non-COVID mortality.

Cellular immunity against SARS-CoV-2 is an important component of the immune response to the virus. At present, two such tests based on interferon-gamma release (interferon-γ release assays, IGRAs) are available—Quan-T-Cell SARS-CoV-2 by EUROIMMUN and T-SPOT.COVID by Oxford Immunotec. In this paper, we compared the results of these two tests in 90 subjects employed at the Public Health Institute Ostrava who had previously undergone COVID-19 infection or were vaccinated against that disease. To the best of our knowledge, this is the first head-to-head comparison of these two tests evaluating T-cell-mediated immunity against SARS-CoV-2. In addition, we also evaluated humoral immunity in the same individuals using the in-house virus neutralization test and IgG ELISA assay. The evaluation yielded similar results for both IGRAs, with Quan-T-Cell appearing to be insignificantly (p = 0.08) more sensitive (all 90 individuals were at least borderline positive) than T-SPOT.COVID (negative results found in five patients). The overall qualitative (presence/absence of immune response) agreement of both tests with virus neutralization test and anti-S IgG was also excellent (close or equal to 100% in all subgroups, with the exception of unvaccinated Omicron convalescents, a large proportion of whom, i.e., four out of six subjects, were IgG negative while at least borderline positive for T-cell-mediated immunity measured by Quan-T). This implies that the evaluation of T-cell-mediated immunity is a more sensitive indicator of immune response than the evaluation of IgG seropositivity. This is true at least for unvaccinated patients with a history of being infected only by the Omicron variant, but also likely for other groups of patients.

Background and Aims: Elderly nursing home residents are especially prone to a severe course of SARS-CoV-2 infection. In this study, we aimed to investigate the complex immune response after vaccination depending on the convalescence status and vaccine. Methods: Sampling took place in September–October 2021. IgG antibodies against spike protein and nucleocapsid protein, the titer of virus neutralization antibodies against delta and (on a subset of patients) omicron, and cellular immunity (interferon-gamma release assay) were tested in nursing home residents vaccinated with Pfizer, Moderna (both 30–31 weeks after the completion of vaccination), or AstraZeneca (23 weeks) vaccines. The prevalence with 95% confidence intervals (CI) was evaluated in Stata version 17. Results: 95.2% (95% CI: 92.5–97.1%) of the 375 participants had positive results of anti-S IgG, 92.8% (95% CI: 89.7–95.2%) were positive in virus neutralization assay against delta, and 89.0% (95% CI: 84.5–92.5%) in the interferon-gamma-releasing assay detecting cellular immunity. Results of the virus neutralization assay against omicron correlated with those against delta but the neutralization capacity was reduced by about half. As expected, the worst results were found for the AstraZeneca vaccine, although the vaccination-to-test period was the shortest for this vaccine. All immune parameters were significantly higher in convalescent residents than in naive residents after vaccination. No case of COVID-19 occurred during the vaccination-to-test period. Conclusions: A high immune response, especially among vaccinated convalescents (i.e., residents with hybrid immunity), was found in elderly nursing home residents 5–7 months after vaccination against SARS-CoV-2. In view of this, it appears that such residents are much better protected from COVID-19 than those who are only vaccinated and the matter of individual approach to the booster dose in such individuals should be further discussed.

Data on the effectiveness of arthroscopic arthrolysis and extraction of osteosynthetic material after osteosynthesis of the proximal humerus in patients with persisting problems are rare and insufficient. In this study, we performed arthroscopic arthrolysis and extraction of fixation screws, and, where protruding, extraction of the nail in 34 patients with problems persisting 12 months after osteosynthesis of the proximal humerus using an intramedullary nail. The effectiveness of the treatment was assessed using the Constant–Murley shoulder score and forward flexion difference between the treated arm and the contralateral one. A median increase of 16 points in CMS score and 30 degrees reduction in the arm forward flexion difference was recorded 12 months after the arthroscopy. The improvement was significantly higher in the patient group with intramedullary nail extraction (however, this group had worse pre-operative values and the screw was only extracted where likely to cause problems). The median time to heal was 11 weeks; no serious peri- or post-procedural complications occurred. Mini-invasive arthroscopic arthrolysis combined with extraction of osteosynthetic material proved to be a safe and effective method for treatment of patients after osteosynthesis of the proximal humerus using an intramedullary nail with persisting pain and/or mobility limitation.

Background and Objectives: In patients with orbital floor blowout fracture (OFBF), accurate diagnosis of ocular motility disorder is important for decisions about conservative or surgical therapy. However, the accuracy of the traditional test for detecting binocular diplopia/ocular motility disorder using a moving pencil or finger (hereinafter, “finger test”) has been generally accepted as correct and has not been subject to scrutiny so far. Hence, its accuracy relative to full orthoptic examination is unknown. Materials and Methods: In this paper, the results of the “finger test” were compared with those derived from a complex examination by orthoptic tests (considered “true” value in patients with OFBF). Results: “Finger test” detected ocular motility disorder in 23% of patients while the full orthoptic examination proved much more efficient, detecting ocular motility disorder in 65% of patients. Lancaster screen test and test with color filters were the most important tests in the battery of the orthoptic tests, capable of identifying 97.7% and 95.3% of patients with ocular motility disorder, respectively. Still, none of the tests were able to correctly detect all patients with ocular motility disorder in itself. Conclusions: As the presence of ocular motility disorder/binocular diplopia is an important indication criterion for the surgical solution of the orbital floor blowout fracture, we conclude that a complex orthoptic evaluation should be always performed in these patients.

Many studies reported good performance of nasopharyngeal swab-based antigen tests for detecting SARS-CoV-2-positive individuals; however, studies independently evaluating the quality of antigen tests utilizing anterior nasal swabs or saliva swabs are still rare, although such tests are widely used for mass testing. In our study, sensitivities, specificities and predictive values of seven antigen tests for detection of SARS-CoV-2 (one using nasopharyngeal swabs, two using anterior nasal swabs and four using saliva) were evaluated. In a setting of a high-capacity testing center, nasopharyngeal swabs for quantitative PCR (qPCR) were taken and, at the same time, antigen testing was performed in accordance with manufacturers’ instructions for the respective tests. In samples where qPCR and antigen tests yielded different results, virus culture was performed to evaluate the presence of the viable virus. Sensitivities and specificities of individual tests were calculated using both qPCR and qPCR corrected for viability as the reference. In addition, calculations were also performed for data categorized according to the cycle threshold and symptomatic status. The test using nasopharyngeal swabs yielded the best results (sensitivity of 80.6% relative to PCR and 91.2% when corrected for viability) while none of the remaining tests (anterior nasal swab or saliva-based tests) came even close to the WHO criteria for overall sensitivity. Hence, we advise caution when using antigen tests with alternative sampling methods without independent validation.

Antigen testing for SARS-CoV-2 is considered to be less sensitive than the standard reference method – real-time PCR (RT-PCR). It has been suggested that many patients with positive RT-PCR ‘missed’ by antigen testing might be non-infectious. In a real-world high-throughput setting for asymptomatic or mildly symptomatic patients, 494 patients were tested using RT-PCR as well as a single lateral flow antigen test (Ecotest, AssureTech, China). Where the results differed, virus viability was evaluated by cell culture. The test parameters were calculated with RT-PCR and RT-PCR adjusted on viability as reference standards. The overall sensitivity of the used antigen test related to the RT-PCR only was 76.2%, specificity was 97.3%. However, 36 out of 39 patients ‘missed’ by the antigen test contained no viable virus. After adjusting on that, the sensitivity grew to 97.7% and, more importantly for disease control purposes, the negative predictive value reached 99.2%. We propose that viability testing should be always performed when evaluating a new antigen test. A well-chosen and validated antigen test provides excellent results in identifying patients who are shedding viable virus (although some caveats still remain) in the real-world high-throughput setting of asymptomatic or mildly symptomatic individuals.