Correlation between specific antibody response to wild-type BNT162b2 booster and the risk of breakthrough infection with omicron variants: Impact of household exposure in hospital healthcare workers.

BACKGROUND: The emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. METHODS: This prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-γ levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. RESULTS: Of 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-γ levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12-0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88-18.40] vs. 2.82 [1.37-5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). CONCLUSIONS: Spike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

No significant influence of pre-vaccination antipyretic use on specific antibody response to a BNT162b2 vaccine booster against COVID-19.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474-21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563-18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Correlation of Postvaccination Fever With Specific Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 BNT162b2 Booster and No Significant Influence of Antipyretic Medication.

Background: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine booster elicits sufficient antibody responses that protect against coronavirus disease 2019, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 2-dose primary series. Spike-specific immunoglobulin G (IgG) titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for 7 days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (ß = .305, P < .001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk, 3.97 [95% confidence interval, 2.48-6.35]); however, the IgG titers after the booster dose were not associated with the presence or degree of fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions should not interfere with the elevation of specific IgG titers.

Post-vaccination antibody evaluation for nosocomial SARS-CoV-2 delta variant breakthrough infection.

Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.

Relation of fever intensity and antipyretic use with specific antibody response after two doses of the BNT162b2 mRNA vaccine.

BACKGROUND: The reactogenicity of BNT162b2 COVID-19 vaccine has been commonly reported and antipyretic medications are often used for mitigating adverse reactions. Possible associations between the reactogenicity events and specific antibody responses have not been fully investigated, nor has the influence of using antipyretics. METHODS: Serum samples were collected from hospital healthcare workers with no COVID-19 history and the SARS-CoV-2 spike-specific IgG titer after two doses was measured. Degree of solicited adverse reactions in a day, including the highest body temperature, were reported using a self-reporting diary for five days after each dose. The highest body temperature during the five days was divided into three grades (<37.0 °C, 37.0-37.9 °C, or ≥ 38.0 °C). Self-medicated antipyretics were reported using a questionnaire. RESULTS: The data of 335 participants were available for analysis. Multivariate analysis extracted the fever grade after the second dose (standardized coefficient beta = 0.301, p < 0.0001), female sex (beta = 0.196, p = 0.0014), and age (beta = -0.119, p = 0.0495) as being significantly correlated with the IgG titers. The positive correlation of the fever grade after the second dose with the IgG titers was also observed when analyzed by sex and age. The use of antipyretics did not interfere with the IgG titers irrespective of the fever grade. CONCLUSIONS: The fever intensity after the second dose was associated with the IgG titer and antipyretic medications may be beneficial to mitigate the suffering from adverse reactions, without interfering with the acquisition of sufficient antibody responses.

Parotitis caused by Mycobacteroides abscessus subspecies abscessus.

Rapidly growing mycobacteria rarely causes parotitis. We report a rare case of Mycobacteroides abscessus subspecies abscessus (MAB) parotitis in a previously healthy 26-year-old woman. She presented to the previous hospital with a swelling over the right parotid region, and a computed tomography scan revealed multiple abscesses in the swollen parotid gland. Histopathology showed granulomatous inflammation with acid-fast bacilli; however, a subsequent culture failed to isolate mycobacterium. Despite repeated antibiotic therapy and multiple surgical interventions including partial incision and drainage of the abscesses, the parotitis did not resolved. At six months after presentation, she was referred to our institute. We performed enlarged resection of the necrotic tissue and abscesses, and the sample cultivated after homogenization was positive for mycobacterium. The isolate was finally identified as MAB. She underwent long-term postoperative antibiotic therapy for MAB, with a favorable outcome. To the best of our knowledge, this is the first case of MAB parotitis where the subspecies has been identified. MAB is much more intractable than the other subspecies. We highlight the importance of the correct identification of MAB, which leads to the appropriate treatment.

The first case of COVID-19 pneumonia in a hemodialysis patient in Japan.

On 31 December 2019, cases of pneumonia whose cause was later identified as SARS-CoV-2 were detected in Wuhan City, Hubei Province of China, and now COVID-19 has spread worldwide. On March 1, 2020, a 69-year-old Japanese man who had been on hemodialysis for 3 years was diagnosed as having COVID-19 pneumonia and hospitalized at our Medical Center. Pulmonary CT revealed bilateral multiple consolidation with bilateral pleural effusion. Aggressive weight reduction was needed to improve the patient's respiratory condition. Hemodialysis therapy was performed in isolation with hydroxychloroquine administration, but the formation of a dialysis membrane clot forced the withdrawal of dialysis therapy. Changing the dialysis membrane material and anticoagulant enabled the resumption of dialysis therapy, allowing the body weight to correct downward. On the 5th hospitalization day, the patient's fever dropped and he showed improved oxygenation and chest X-ray. He was eventually discharged. The hydroxychloroquine and appropriate fluid management may have contributed to the patient's recovery. Clinicians should pay close attention to avoid dialysis-related problems when treating a patient with COVID-19.