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IntroductionIn addition to the original monovalent vaccines available for SARS-CoV-2, bivalent vaccines covering wild-type (WT) and Omicron BA.1 are also available. However, there is a lack of real-world data on the effectiveness of bivalent vaccines as second boosters on the dominant Omicron sublineages, including BA.2 and BA.5. MethodsThis prospective longitudinal cohort study was conducted at Toyama University Hospital, a tertiary medical center in Japan. Participants (n = 565) who received the first booster vaccination were followed up until 2 weeks after the second booster dose of the monovalent mRNA-1273 (WT group, n = 168) and bivalent BNT162b2 (WT+BA.1 group, n = 23) vaccines. Participants with previous SARS-CoV-2 infections were excluded from the study. Anti-receptor-binding domain (RBD) antibody levels and neutralizing activity were measured. Vaccine-related symptoms were also assessed using a questionnaire after the second booster dose. ResultsThe anti-RBD antibody levels after the second booster dose in the WT and WT+BA.1 group were similar (median [inter quartile], 26262.0 [16951.0-38137.0] U/mL vs. 24840.0 [14828.0-41460.0] U/mL, respectively). Although the neutralization activity of the pooled sera of the WT+BA.1 group was the lowest against BA.5, the activities against BA.2 and BA.5 were higher than those of the WT group in both pseudotyped and live virus assays. Vaccine-related symptoms, including systemic and local symptoms, were strongly correlated with anti-RBD antibody levels and neutralizing titers with significant differences. ConclusionThe second booster dose of the bivalent (WT/Omicron BA.1) vaccine induced higher neutralizing activity against BA.2 and BA.5 than that of the original monovalent vaccine.
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IntroductionThe vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster. MethodsSerum samples were obtained from healthcare workers (20-69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires. ResultsThe median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0-1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0->25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever [≥]37.5 {degrees}C, general fatigue, and myalgia, local swelling, and local hardness. ConclusionThe booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.
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ObjectivesVaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate whether the vaccine provides protective immunity effectively, the amount and function of vaccine-induced antibodies were evaluated. MethodsSera from 13-17 days after the second dose of the Pfizer BNT162b2 vaccine were collected from healthcare workers at the University of Toyama (n=740). Antibody levels were quantitatively measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralising activity against pseudotyped viruses displaying wild-type (WT) and mutant spike proteins (B.1.1.7- and B.1.351-derived variants) were assayed using a high-throughput chemiluminescent reduction neutralising test (htCRNT). Basic clinical characteristics were obtained from questionnaires. ResultsAntibodies were confirmed in all participants in both the anti-RBD test (median 2112 U/mL, interquartile range [IQR] 1275-3390 U/mL) and the htCRNT against WT (median % inhibition >99.9, IQR >99.9 to >99.9). For randomly selected sera (n=61), 100.0% were positive for htCRNT against the B.1.1.7- and B.1.351-derived variants. Among those who answered the questionnaire (n=237), the values of the anti-RBD test were negatively correlated with age for females (p<0.01; r = -0.31, 95% confidence interval -0.45 to -0.16). Systemic symptoms after vaccination were related to higher values of the anti-RBD test (median 2425, IQR 1450 - 3933 vs. median 1347, IQR 818 - 2125 for no symptoms; p<0.01). ConclusionsThe BNT162b2 vaccine produced sufficient antibodies in terms of quality and quantity which could neutralise emerging variants. Antibody induction can be affected by age and sex but will still be at a sufficient level.
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BackgroundSerological tests are beneficial for recognizing the immune response against SARS-CoV-2. To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT), using pseudotyped SARS-CoV-2, is critical. Whether commercial antibody tests are comparably accurate is unknown. MethodsSerum samples collected before variants were locally found were obtained from confirmed COVID-19 patients (n = 74), confirmed non-COVID-19 individuals (n = 179), and unscreened individuals (suspected healthy individuals, n = 229). The convalescent phase was defined as the period after day 10 from disease onset. The CRNT against pseudotyped viruses displaying the wild-type spike protein and a commercially available anti-receptor binding domain (RBD) antibody test were assayed. The CRNT was also assayed, using South African (SA) and United Kingdom (UK)-derived variants. ResultsThe CRNT (cut off value, 50% inhibition) and the anti-RBD antibody test (cut off value, 0.8 U/mL) concurred regarding symptomatic COVID-19 patients in the convalescent phase and clearly differentiated between patients and suspected healthy individuals (sensitivity; 95.8% and 100%, specificity; 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titer (r = 0.47, 95% CI 0.20-0.68). Compared with the wild-type, CRNT reduction was observed for the SA and UK-derived variants. Of the samples with [≥]100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed [≥]50% neutralization against the UK and the SA variants, respectively. ConclusionThe CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. The strong positive results using the commercial antibody test can reflect neutralizing activity against emerging variants.
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IntroductionAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Patients and MethodsUsing SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. ResultsOf the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P=.0011). ConclusionsNeutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.
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ObjectiveThis study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. MethodsAn analytical cross-sectional study was performed in a single tertiary care hospital and included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables, including required oxygen supplementation, ICU admission, invasive mechanical ventilation, and in-hospital mortality, were examined. ResultsFifty-six patients were included in the study. The median age was 54.5 years, and individuals with RNAemia were older than those without detectable SARS-CoV-2 RNA in serum (78 vs. 50 years; P = .0013). RNAemia was detected in 19.6% of patients (11/56) and in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) of moderate, severe, and critically ill cases, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%; P < .0001) and ICU admission (81.8% vs. 6.7%; P < .0001) and required invasive mechanical ventilation (27.3% vs. 0.0%; P < .0001). Among patients with RNAemia, the median viral loads of NP swabs that were collected around the same time as the serum were significantly higher in critically ill cases (5.4 Log10 copies/L [IQR: 4.2-6.3]) than in moderate-severe cases (2.6 Log10 copies/L [1.1-4.5]; P =.030) and were significantly higher in nonsurvivor cases (6.2 Log10 copies/L [IQR: 6.0-6.5]) than in survivor cases (3.9 Log10 copies/L [1.6-4.6]; P =.045). ConclusionsThis study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with severity and mortality, thus suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19 with a higher quality than each separate test.
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SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an immunofluorescence assay (IFA). The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.
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To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19), we reviewed epidemiological and clinical data obtained from immunocompetent laboratory-confirmed patients with COVID-19 at Toyama University Hospital. In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in adults than in children and in symptomatic than in asymptomatic patients. Among symptomatic patients, non-linear regression models showed that the estimated viral load at onset was higher in the index (patients who transmitted the disease to at least one other patient) than in the non-index patients (patients who were not the cause of secondary transmission; median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/L, respectively). High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Article Summary LineHigh nasopharyngeal viral load around the onset may contributes to secondary transmission of COVID-19.
