A questionnaire-based survey of COVID-19 transmission in dental practice during the pandemic:comparison between the 1st-5th and the 6th-8th surges in Japan (preprint)

Background: Previously, we conducted a questionnaire survey on infection control measures and infection status among practicing dentists in Nagano prefecture, Japan, between February 2020 and September 2021 (1-5th surge of COVID-19 cases in Japan) and found that the risk of COVID-19 infection spreading through dental care was very low. However, it was noted that the low number of infected patients during the survey period may have been a contributing factor. Subsequently, an explosive increase in the number of infected patients was observed, raising the possibility of nosocomial infections in dental treatment settings. Therefore, in this study, we reexamined the infection situation in dental care settings at the time of infection spread and compared the results with those of previous reports. Materials and methods An online questionnaire-based survey on clinical activities, infection control measures, and confirmed or probable COVID-19 cases among patients and clinical staff were conducted between February 2022 to March 2023 (6-8th surge). Results The number of COVID-19 positive patients increased approximately 50-fold between the study periods. There was a 3.5-fold increase in the rate of treatment for infected patients. Even with the increased likelihood of contact with COVID-19 patients, no cases of infection during dental treatment were observed. Conclusions The results of this study indicate that even with the possibility of contact with COVID-19 during dental treatment, the likelihood of COVID-19 clusters occurring in dental practices is low if appropriate infection prevention measures are in place.

A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients (preprint)

We previously reported that a second dose of COVID-19 mRNA vaccine was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. However, some of these patients did not achieve seroconversion. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in Japanese allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of COVID-19 mRNA vaccine. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID19 mRNA vaccine (BNT162b2 [n = 15] and mRNA1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Median time from HSCT to the third vaccination and from the second to the third vaccination was 1842 (range, 378-4279) days and 219 (range, 194-258) days, respectively. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Median optical density of S1 IgG titers before and after the third dose was 0.099 (range, 0.001-0.713) and 1.315 (range, 0.006-1.730), respectively. Among 22 evaluable patients, 21 (95%) seroconverted after the third dose. Four of the five patients treated with steroids or CI seroconverted after the third vaccination. One patient with a serum IgG level of 173 mg/dL who received steroids did not achieve seroconversion. On one-week follow-up, none of our patients had > grade 3 or serious adverse events, new onset graft versus host disease (GVHD), or GVHD exacerbation after vaccination. The most frequent adverse event was mild pain at the injection site. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.

Promising efficacy of following a third dose of mRNA SARS-CoV-2 vaccination in patients treated with anti-CD20 antibody who failed 2-dose vaccination (preprint)

Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for S1 protein after third vaccination in 22 patients treated with anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving seroconversion rate in patients treated with anti-CD20 antibody who failed standard two-dose vaccination.

Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in Japanese patients after allogeneic stem cell transplantation. (preprint)

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccine in HSCT patients remains to be investigated. We prospectively evaluated the safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) got seroconversion of anti-S1 IgG. Median optical density of antibody levels in HSCT patients with low IgG levels (< 600 mg/dL), steroid treatment, or low lymphocytes (< 1000 /L) was significantly lower than that in the other HSCT patients. There were no serious adverse events (> Grade 3), no new development or exacerbation of graft-versus-host disease after vaccination. We concluded BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.

Safety and Immunogenicity of the COVID-19 Vaccine BNT162b2 in Patients Undergoing Chemotherapy for Solid Cancer (preprint)

Background: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. Methods: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. Results: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. Conclusion: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.

Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients in outbreak on a cruise ship (preprint)

Background A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients. Methods Blood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples. Results Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein, were significantly lower in blood samples with false-negative results than in those with positive results. Conclusions These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines, and situations in which it is useful are limited.