Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection.

BACKGROUND: Before the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea. METHODS: The two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases. RESULTS: There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02-97.61%, SVNT-O: 15.18-42.29%) group than in the BBB group (SVNT-WT: 89.19-98.11%, SVNT-O: 23.58-68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group. CONCLUSION: The cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.

Immune Responses against the Omicron Variant of SARS-CoV-2 after a Third Dose of COVID-19 Vaccine in Patients Living with Human Immunodeficiency Virus (PLWH): Comparison with Healthcare Workers.

We compared immune responses against the omicron variant of SARS-CoV-2 after a third dose of the coronavirus disease 2019 (COVID-19) vaccine between people living with human immunodeficiency (PLWH) and healthcare workers (HCWs). In this prospective observational study, PLWH and HCWs vaccinated with at least two doses of vaccine were enrolled. We analyzed neutralizing responses using the GenScript SARS-CoV-2 surrogate virus neutralization test kit. Twenty-nine PLWH and 114 HCWs were included to analyze immune responses after the third vaccination. Most PLWH (86.2%) had fully suppressed viral loads and CD4 T cell counts were well-controlled (median 670.0 cells/µL). The neutralizing responses against the omicron variant in PLWH were not significantly different from those in HCWs (43.94% vs. 51.77%, p = 0.42). However, neutralizing responses against the omicron variant were significantly impaired by about 50% compared with wild type SARS-CoV-2 in PLWH (43.94% vs. 97.46%, p < 0.001) and HCWs (51.77% vs. 97.74%, p < 0.001). Although neutralizing responses against the omicron variant in well-controlled PLWH were comparable to those of HCWs, the responses were much lower than those against wild type in both PLWH and HCWs. Therefore, the risk of breakthrough SARS-CoV-2 infection due to the currently circulating omicron variant is still high despite three doses of vaccine in PLWH and will not differ from HCWs.

Immunogenicity against the Omicron Variant after mRNA-Based COVID-19 Booster Vaccination in Medical Students Who Received Two Primary Doses of the mRNA-1273 Vaccine.

We evaluated the immune response against the Omicron variant after mRNA-based COVID-19 booster vaccination in medical students. We prospectively enrolled medical students who received two primary doses of the mRNA-1273 vaccine. The neutralizing response and the SARS-CoV-2-specific T-cell response was evaluated. A total of 56 serum samples were obtained before booster vaccination. Nineteen students (33.9%) developed COVID-19 two months after booster vaccination. Of 56 students, 35 students (12 infected and 23 uninfected) were available for blood sampling four months after booster vaccination. In comparison with uninfected students, infected students showed a significantly higher level of SARS-CoV-2-specific IgG (5.23 AU/mL vs. 5.12 AU/mL, p < 0.001) and rate of neutralizing response (96.22% vs. 27.18%, p < 0.001) four months after booster vaccination. There was no significant difference in the SARS-CoV-2-specific T-cell response. Among 23 infection-naive students, the neutralizing response was significantly higher in those who received the mRNA-1273 booster than in those who received the BNT162b2 booster (69.07% vs. 26.43%, p = 0.02). In our study, booster vaccination with mRNA-1273 instead of BNT162b2 was significantly associated with a higher neutralizing response.

Positivity of Rapid Antigen Testing for SARS-CoV-2 With Serial Followed-up Nasopharyngeal Swabs in Hospitalized Patients due to COVID-19.

Despite the accuracy of nucleic acid amplification tests (NAATs), rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus-2 are widely used as point-of-care tests. A total of 282 pairs of reverse transcription-polymerase chain reaction and Standard Q COVID-19 Ag tests were serially conducted for 68 patients every 3-4 days until their discharge. Through a field evaluation of RATs using direct nasopharyngeal swabs, the sensitivities were 84.6% and 87.3% for E and RNA-dependent RNA polymerase (RdRp) genes, respectively, for specimens with cycle thresholds (Cts) < 25. The Ct values of E and RdRp genes for 95% detection rates by RATs were 16.9 and 18.1, respectively. The sensitivity of RAT was 48.4% after the onset of symptoms, which was not sufficient. RAT positivity gradually decreased with increased time after symptom onset and had continuously lower sensitivity than NAATs.

Relationship between SARS-CoV-2 antibody titer and the severity of COVID-19.

BACKGROUND: It remains unclear whether high titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies aggravate clinical manifestations in patients or whether severe clinical manifestations result in high antibody titers. Thus, we investigated the cause-effect relationship between SARS-CoV-2 antibody titers and disease severity. METHODS: We prospectively enrolled patients admitted with the diagnosis of coronavirus disease-19 (COVID-19) from February 2020 to August 2020. We measured SARS-CoV-2 antibody titers, namely anti-receptor-binding domain (RBD) antibody and neutralizing antibody (NAb), from blood samples and calculated the chest radiograph (CXR) scores of the patients to evaluate the severity of COVID-19. RESULTS: Overall, 40 patients with COVID-19 were enrolled. Pneumonia was observed in more than half of the patients (25/40, 60%). SARS-CoV-2 antibody titers were higher in patients who were aged >60 years (anti-RBD antibodies, P = 0.003 and NAb, P = 0.009), presented with pneumonia (P = 0.006 and 0.007, respectively), and required oxygen therapy (P = 0.003 and 0.004, respectively) than in those who were not. CXR scores peaked (at 15-21 days after the onset of symptoms) statistically significantly earlier than SARS-CoV-2 antibody titers (at 22-30 days for NAb and at 31-70 days for anti-RBD antibody). There was a close correlation between the maximum CXR score and the maximum SAR-CoV-2 antibody titer. CONCLUSIONS: Based on the comparison of the peak time of SARS-CoV-2 antibody titers with the CXR score after symptom onset, we suggest that severe clinical manifestations result in high titers of SARS-CoV-2 antibodies.