ABSTRACT
We identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
ABSTRACT
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.
ABSTRACT
The VOC of SARS-CoV-2, Omicron (BA.1, BA.1.1, BA.2, or BA.3), is associated with an increased risk of reinfection. BA.2 has become the next dominant variant worldwide. Although BA.2 infection has been shown to be mild illness, its high transmissibility will result in high numbers of cases. In response to the surge of Omicron BA.1 cases, booster vaccination was initiated in many countries. But there is limited evidence regarding the effectiveness of a booster vaccination against BA.2. We collected blood samples from 84 physicians at Kobe University Hospital, Japan, in January 2022 [~]7 months after they had received two BNT162b2 vaccinations and [~]2 weeks after their booster vaccination. We performed a serum neutralizing assay against BA.2 using authentic virus. Although most of the participants had no or a very low titer of neutralizing antibody against BA.2 at 7 months after two BNT162b2 vaccinations, the titer increased significantly at 2 weeks after the booster vaccination.
ABSTRACT
The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Surprisingly and interestingly, after the second vaccination, the subjects neutralizing antibody titers including that against Omicron all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the subjects disease severity. Our findings thus demonstrate that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.
ABSTRACT
To investigate the induction of neutralizing antibodies against Omicron after two and three vaccine doses in recipients of different ages. Physicians at Kobe University Hospital who had received the second dose of the BNT162b2 mRNA vaccine. At 2 months after the second vaccinations, the positive rate of neutralizing antibody against Omicron was 28%, and the titer was significantly lower than those against other variants, 11.8-fold and 3.6-fold lower than those against D614G and Delta, respectively. Unlike Delta, that positive rates of neutralizing antibody against Omicron were low in all age groups, and there was no significant difference in titers among age groups. Seven months after the 2nd dose, the positive rate of neutralizing antibody against Omicron decreased to 6%, but after the booster,3rd vaccination, it increased to 100%, and the titer was much higher than those at 2 and 7 months post-vaccination, 32-fold and 39-fold respectively. The booster vaccination effect was also observed in the younger at 41-fold, middle-aged at 43-fold, and older at 27-fold groups compared to the 7-month titers. Surprisingly, higher-than-predicted titers of the neutralizing antibodies against Omicron were induced after the booster vaccination regardless of recipient age, while this effect was not observed after two doses, indicating the induction of antibodies against common epitopes by the booster vaccination. Three doses can be confidently recommended to suppress the pandemic.
ABSTRACT
BackgroundThe COVID-19 pandemic situation has been changing drastically worldwide due to the continuous appearance of SARS-CoV-2 variants and the roll-out of mass vaccination. Periodic cross-sectional studies during the surge of COVID-19 cases is essential to elucidate the pandemic situation. MethodsSera of 1,000 individuals who underwent a health check-up in Hyogo Prefecture Health Promotion Association clinics in Japan were collected in August and December 2021. Antibodies against SARS-CoV-2 N and S antigens were detected in the sera by an electrochemiluminescence immunoassay (ECLIA) and an enzyme-linked immunosorbent assay (ELISA), respectively. The seras neutralization activities for the conventional SARS-CoV-2 (D614G), Delta, and Omicron variants were measured. ResultsThe seropositive rates for the antibody against N antigen were 2.1% and 3.9% in August and December 2021 respectively, demonstrating a Delta variant endemic during that time; the actual infection rate was approximately twofold higher than the rate estimated based on the polymerase chain reaction (PCR)-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. ConclusionsThese analyses revealed that herd immunity against SARS-CoV-2 including the Delta variant was established in December 2021, leading to convergence of the variants. The low neutralizing activity against the Omicron variant suggests the need for the further promotion of the prompt three-dose vaccination to overcome this variants imminent 6th wave in Japan. SummarySeroepidemiologic study of COVID-19 on December 2021 in Japan showed neutralizing antibodies for Delta were 78.7%, indicating the acquisition of herd immunity by mass vaccination leading to convergence while those for Omicron were only 36.6%, indicating need of booster vaccination.
ABSTRACT
BACKGROUND@#We investigated whether family histories of herpes zoster (HZ) are associated with the risk of incident HZ in a Japanese population.@*METHODS@#A total of 12,522 Japanese residents aged ≥50 years in Shozu County participated in the baseline survey between December 2008 and November 2009 (the participation rate = 72.3%). They were interviewed at baseline by research physicians regarding the registrants' history of HZ. A self-administered questionnaire survey was conducted to evaluate the potential confounding factors. 10,530 participants without a history of HZ were followed up to ascertain the incidence of HZ during 3-years follow-up until the end of November 2012 with Japanese nationals. We estimated hazard ratios (HRs) of incident HZ according to first-degree family histories using the Cox proportional hazard regression after adjusting for age, sex, and other potential confounding factors.@*RESULTS@#Compared to no HZ history of each family member, a history of brother or sister was associated with a higher risk of incident HZ while histories of father and mother were not. The multivariable HR (95%CI) of incident HZ for a history of brother or sister was 1.67 (1.04-2.69). When comparing to no family histories of all first-degree relatives, the multivariable HRs (95%CIs) were 1.34 (0.77-2.34) for a history of brother or sister alone, but 4.81 (1.78-13.00) for a history of mother plus brother or sister. As for the number of family histories, the multivariable HRs (95%CIs) were 1.08 (0.76-1.54) for one relative (father, mother, or brother or sister) and 2.75 (1.13-6.70) for two or more relatives.@*CONCLUSION@#Family histories of mother plus brother or sister and two or more first-degree relatives were associated with a higher risk of incident HZ.
Subject(s)
Female , Humans , Male , Herpes Zoster/epidemiology , Incidence , Mothers , Proportional Hazards ModelsABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is transmitted by droplet and contact infection. SARS-CoV-2 that adheres to environmental surfaces remains infectious for several days. We herein attempted to inactivate SARS-CoV-2 and influenza A virus adhering to an environmental surface by spraying aerosolized hypochlorous acid solution and hydrogen peroxide solution in the form of Dry Fog (fog that does not wet objects even if touched). SARS-CoV-2 and influenza virus were dried on plastic plates and placed into a test chamber for inactivation by the Dry Fog spraying of disinfectants. The results obtained showed that Dry Fog spraying inactivated SARS-CoV-2 and influenza A virus in time- and exposed disinfectant amount-dependent manners. SARS-CoV-2 was more resistant to the virucidal effects of aerosolized hypochlorous acid solution and hydrogen peroxide solution than influenza A virus; therefore, higher concentrations of spray solutions were required to inactivate SARS-CoV-2 than influenza A virus. The present results provide important information for the development of a strategy that inactivates SARS-CoV-2 and influenza A virus on environmental surfaces by spatial spraying.
ABSTRACT
BackgroundAlthough 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. MethodsWe 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. ResultsAnti-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. ConclusionAlthough 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. Mini abstractTiters of anti-S1 antibody after the second dose of BNT162b2 were significantly lower in patients with solid tumors undergoing active anticancer treatment than in the healthy volunteers.
ABSTRACT
The situation of the COVID-19 pandemic in Japan is drastically changing in the 2nd year, 2021, due to the appearance of SARS-CoV-2 variants of concern and the roll-out of mass vaccination. In addition to PCR diagnosis, periodic seroepidemiologic surveillance is important to analyze the epidemic situation. In this study, we analyzed the rate of seropositivity for the SARS-CoV-2 N and S antigens in Hyogo prefecture, Japan in August 2021. Sera collected from people who received a health check-up in a clinic of the Hyogo Prefecture Health Promotion Association were subjected to analysis of reactivity to the SARS-CoV-2 N and S antigens by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA), respectively. For a total 1,000 sera, the positive rates to N and S antigens were 2.1% and 38.7%, respectively. The infectious rate estimated by serological analysis based on the presence of the anti-N antibody was 2.5-fold higher than the value reported based on PCR-based analysis, and it increased five-fold compared to the rate determined by our previous seroepidemiologic study in October, 2020. The anti-S positive rate was almost consistent with the vaccination rate in this area. The observed high anti-S antibody level in the seropositive population may indicate that the mass vaccination in Japan is being performed smoothly at this time point, although the infectious rate has also increased.
ABSTRACT
In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. We investigated the neutralizing potency of 81 COVID-19 patients sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses. Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351.
ABSTRACT
BackgroundCOVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established. MethodsWe serially collected 45 blood samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients clinical courses. ResultsAll 12 individuals infected with SARS-CoV-2 had the neutralizing antibody against it, and the antibodies were induced at approx. 4-10 days after the patients onsets. The antibodies in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms. ConclusionNeutralizing antibodies against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease severity. These results may indicate that plasma or neutralizing antibody therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genomes disappearance.
ABSTRACT
The analysis of systematically collected data for COVID-19 infectivity and death rates has revealed in many countries around the world a typical oscillatory pattern with a 7-days (circaseptan) period. Additionally, in some countries the 3.5-days (hemicircaseptan) and 14-days periodicities have been also observed. Interestingly, the 7-days infectivity and death rates oscillations are almost in phase, showing local maxima on Thursdays/Fridays and local minima on Sundays/Mondays. These observations are in stark contrast with a known pattern, correlating the death rate with the reduced medical staff in hospitals on the weekends. One possible hypothesis addressing these observations is that they reflect a gradually increasing stress with the progressing week, which can trigger the maximal death rates observed on Thursdays/Fridays. Moreover, assuming the weekends provide the likely time for new infections, the maximum number of new cases might fall again on Thursdays/Fridays. These observations deserve further study to provide better understanding of the COVID-19 dynamics.
