ABSTRACT
Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , Prospective Studies , COVID-19/prevention & control , SARS-CoV-2 , Immunoglobulin A , Immunoglobulin GABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths1-4. Diagnostic tools and serological assays are critical for controlling the outbreak5-7, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection8-11. As vaccines become increasingly available12, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside of biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization9,10,13,14. Here we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped VSV virus neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase and secreted embryonic alkaline phosphatase (SEAP) expressing pseudotyped virus neutralizations, followed by GFP expressing pseudotyped virus neutralization, and then the ELISAs.
ABSTRACT
<p><b>BACKGROUND</b>After anterior cruciate ligament (ACL) reconstruction, some patients suffered from sensory disturbance around the surgical incision of the leg. This research was aimed to investigate the relationship between the different skin incisions and the injury of the infrapatellar branch of the saphenous nerve (IPBSN) post ACL reconstruction.</p><p><b>METHODS</b>ACL reconstructions were performed with quadruple hamstring tendon for 60 patients. Sensory disturbance around the skin incision was followed up at an average of 14.5 +/- 4.7 months post operation. Among the 60 patients, vertical incision for 35 patients and oblique incision for 25 patients were used for graft taking during ACL reconstruction. The lengths of the incisions were measured. The patients were asked to mark the sensory disturbance zone at follow up time, and then the marked area was measured. The IPBSN of 15 cadaver knees were anatomized. The distance between the IPBSN and the upper edge of the pes anserinus tendon at the middle point of the incision was measured. Independent-samples t-test, chi-square and Mann-Whitney tests were used for statistical analyses.</p><p><b>RESULTS</b>The patients' age (P = 0.329), the follow-up time (P = 0.681), and the incision length (P = 0.732) between the two groups had no significant difference. Twenty-three patients (65.7%) in the vertical incision group had IPBSN injury compared with 6 patients (24.0%) in oblique incision group (P = 0.002). The average sensory disturbance area in vertical incision group ((48.0 +/- 75.3) cm(2)) was significantly larger (P = 0.004) than that in the oblique group ((8.4 +/- 19.4) cm(2)). The anatomy measurement showed the average distance between IPBSN and the upper edge of the pes anserinus tendon was 0.6 cm at the incision.</p><p><b>CONCLUSIONS</b>Oblique incision with less risk of damage for IPBSN may be better for graft harvesting in ACL reconstruction. As the IPBSN is so near and parallel to the hamstring tendons, damage to the IPBSN is one of the potential complications for graft harvesting, regardless of the incision used. That's why even in the oblique incision group, 24% patients also had sensory disturbance complication.</p>
