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Background: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose.Methods: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys.Results: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events.Conclusions: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. Methods We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. Results Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E−5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E−4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. Conclusions Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health. [ABSTRACT FROM AUTHOR]

Since its introduction as a mass-screen parameter for early detection of prostate cancer, PSA was credited for a significant revolution in the management of prostate disease. But over 2 decades of global experience with this marker have emphasized that the recommended threshold value of 4.0 ng/ml may not be valid in distinguishing tumor growth from benign proliferation of the prostate in over 30% of the cases. Hence, more advanced tools of PSA evaluation have been introduced such as "PSA velocity", "PSA density" or age-related PSA". Recently, precursor molecules of PSA were identified, which are assumed to be zymogen structures devoid of proteolytic activity. These precursor species known as pro-PSAs possess an additional "tail" ranging in size from 2 to 7 extra amino acids at the N terminus of PSA, and represent a fraction of the non-complex or "free PSA", that has usually been identified as a marker for non-cancerous proliferation of the prostate. Interestingly, one of these proPSA structures in particular, [-2]proPSA, has demonstrated to be more specifically indicative of prostate tumor growth in numerous clinical studies. Lately, a chemiluminescence kit has been approved by the European Health Agency as a more specific marker for diagnosis of prostate malignancy, mostly in men with PSA levels ranging from 2-10 ng/ml.