Decreased community-acquired pneumonia coincided with rising awareness of precautions before governmental containment policy in Japan.

The effectiveness of population-wide compliance to personal precautions (mask-wearing and hand hygiene) in preventing community-acquired pneumonia has been unknown. In Japan, different types of nonpharmaceutical interventions from personal precautions to containment and closure policies (CACPs, e.g. stay-at-home requests) were sequentially introduced from late January to April 2020, allowing for separate analysis of the effects of personal precautions from other more stringent interventions. We quantified the reduction in community-acquired pneumonia hospitalizations and deaths and assessed if it coincided with the timing of increased public awareness of personal precautions before CACPs were implemented. A quasi-experimental interrupted time-series design was applied to non-COVID-19 pneumonia hospitalization and 30-day death data from April 2015 to August 2020 across Japan to identify any trend changes between February and April 2020. We also performed a comparative analysis of pyelonephritis and biliary tract infections to account for possible changes in the baseline medical attendance. These trend changes were then compared with multiple indicators of public awareness and behaviors related to personal precautions, including keyword usage in mass media coverage and sales of masks and hand hygiene products. Hospitalizations and 30-day deaths from non-COVID-19 pneumonia dropped by 24.3% (95% CI 14.8-32.8) and 16.1% (5.5-25.5), respectively, in February 2020, before the implementation of CACPs, whereas pyelonephritis and biliary tract infections did not suggest a detectable change. These changes coincided with increases in indicators related to personal precautions rather than those related to contact behavior changes. Community-acquired pneumonia could be reduced by population-wide compliance to moderate precautionary measures.

Estimation of Intangible Costs for Factors Associated with Oral Antiviral Drugs for COVID-19 Treatment: A Conjoint Analysis in Japan.

INTRODUCTION: During the recent coronavirus disease 2019 (COVID-19) pandemic, preferences for factors associated with vaccines have been evaluated. Three oral antiviral drugs have been approved in Japan for patients with mild-to-moderate I COVID-19 symptoms. Although preferences for the drugs may also depend on various factors, these have not been fully evaluated. METHODS: A conjoint analysis was performed based on an online survey in August 2022 to estimate the intangible costs of factors associated with oral antiviral drugs for COVID-19. Respondents were individuals aged 20-69 across Japan. The attributes included the company (Japanese/foreign) that developed the drug, formulation and size of the drug, frequency of administration per day, number of tablets/capsules per dose, number of days until no longer infectious to others, and out-of-pocket expenses. A logistic regression model was applied to estimate the utility of each level for each attribute. The intangible costs were calculated by comparing the utility to the out-of-pocket attribute. RESULTS: Responses were collected from 11,303 participants. The difference between levels was the largest for companies that developed a drug; the intangible costs were JPY 5390 higher for the foreign company than for the Japanese company. The next largest difference was in the number of days until one is no longer infectious. For the same formulation, the intangible cost was lower for small sizes than large sizes. For similar-sized tablets and capsules, the intangible cost was lower for tablets than capsules. These tendencies were similar regardless of COVID-19 infection history and the presence of risk factors for severe COVID-19 in the respondents. CONCLUSION: Intangible costs for factors associated with oral antiviral drugs among the Japanese population were estimated. The results may change as the number of people with a history of COVID-19 infection increases and significant progress is made regarding treatments.

Serological response to a third dose of SARS-CoV-2 vaccine according to previous infection history

The IgG antibody titer against SARS-CoV-2 receptor binding protein (RBD) after mRNA vaccine were compared between those with and without previous infection (PI) for up to 48 weeks. Though sustained higher IgG-RBD were observed in the PI group after two doses of vaccines, both groups benefited from the booster shots of the third vaccine. This data supports the necessity of the booster shots to those with PI.

Serological response to a third dose of SARS-CoV-2 vaccine according to previous infection history.

The IgG antibody titer against SARS-CoV-2 receptor binding protein (RBD) after mRNA vaccine were compared between those with and without previous infection (PI) for up to 48 weeks. Though sustained higher IgG-RBD were observed in the PI group after two doses of vaccines, both groups benefited from the booster shots of the third vaccine. This data supports the necessity of the booster shots to those with PI.

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study.

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization.

Favorable Humoral Response to Third Dose of BNT162b2 in Patients Undergoing Hemodialysis.

Patients undergoing hemodialysis are known to exhibit low humoral responses to vaccines against severe acute respiratory syndrome coronavirus 2. In this study, we aimed to elucidate the humoral response to the third dose of BNT162b2 (Pfizer) in patients undergoing hemodialysis. We included 279 patients undergoing hemodialysis (69 ± 11 years, 65% male, median dialysis vintage: 69 months) and 189 healthcare workers (45 ± 13 years, 30% male) who received the third dose of BNT162b2. Anti-spike immunoglobulin G (anti-S IgG) antibody levels were measured 3-4.5 months after the second dose and 3 weeks after the third dose and were compared. Despite a significant difference in anti-S IgG antibody levels after the second dose between the two groups (patients: median 215 U/mL and healthcare workers: median 589 U/mL; p < 0.001), no significant difference in anti-S IgG antibody levels after the third dose was observed (patients: median 19,000 U/mL, healthcare workers: median 21,000 U/mL). Except for dialysis vintage (ρ = 0.209, p < 0.001), no other factors correlated with anti-S IgG antibody levels after the third vaccine dose in patients undergoing hemodialysis. Therefore, a favorable response to the third dose of BNT162b2 was observed in patients undergoing hemodialysis, irrespective of their backgrounds.

Clinical Evaluation of Conventional Human Coronavirus Infection in Adults.

Human coronaviruses (HCoVs) are distributed globally and they cause a range of respiratory symptoms. Since HCoV infection usually causes mild upper respiratory tract disease and currently has no specific therapy, there are limited reports on its features, especially in adults. We aimed to evaluate the features of HCoV infections in clinical settings. Adult patients with respiratory symptoms from October 2014 to September 2019 at Nagasaki Genbaku Isahaya Hospital were enrolled. Multiplex reverse transcription-polymerase chain reaction as performed for 15 viruses, including HCoVs, and eight bacterial species on the patients' respiratory specimens. A total of 121 cases were recruited with HKU1, OC43, 229E, and NL63 strains in 80, 21, 12, and 11 cases, respectively. The percentage of HCoV-infected patients peaked in winter (47.5%). Symptoms of fever (69.4%), cough (47.9%), and comorbidities of asthma/cough variant asthma (34.7%) were frequently observed. Lymphocytopenia and increased C-reactive protein levels were observed in laboratory tests. Co-infection with other viruses was identified in 38.8% of the cases. In the repeat-positive cases, 42% were repeat positive within 100 days. HCoV-infected patients showed winter seasonality with a high frequency of comorbidity with asthma and co-infections. Re-infection within an early period was suspected, but further consideration is required.

Low humoral immune response to the BNT162b2 vaccine against COVID-19 in nursing home residents undergoing hemodialysis: a case-control observational study.

Background: Patients on hemodialysis (HD) face a high mortality risk from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and they are therefore prioritized for vaccination. However, the efficacy of vaccination in this vulnerable population has not been confirmed. Although age is negatively correlated with serum immunoglobulin (Ig) levels, humoral responses to vaccination in elderly patients undergoing HD have not been investigated. To address this issue, we evaluated the anti-SARS-CoV-2 spike protein antibodies in nursing home residents on HD after BNT162b2 vaccine administration. Methods: Patients on HD from a nursing home and care workers (controls) receiving two doses of the BNT162b2 vaccine between April and May 2021 were enrolled in this study. Those with a prior history of COVID-19 were excluded. Anti-spike protein antibodies were measured with the Elecsys (Roche) immunoassay system. Results: The study included 26 nursing home residents (41% male; median age, 86 years) and 184 care workers (28% male; median age, 45 years). The median HD vintage was 51 months. After two doses of BNT162b2, 73% of the nursing home residents and 99.5% of the control group developed sufficient anti-spike protein antibodies (> 29 U/mL) to neutralize SARS-CoV-2. Three weeks after the second dose, median IgG titers of the residents and care workers were 83 [interquartile range (IQR) 17-511] and 1365 (IQR 847-2245) U/mL, respectively (p < 0.001). Conclusions: The humoral response to BNT162b2 among elderly HD patients was relatively low; therefore, the optimal vaccination strategy for this population should be studied further to avoid COVID-19 outbreaks in healthcare facilities. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00397-5.

Low humoral immune response to the BNT162b2 vaccine against COVID-19 in nursing home residents undergoing hemodialysis: a case–control observational study

Background Patients on hemodialysis (HD) face a high mortality risk from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and they are therefore prioritized for vaccination. However, the efficacy of vaccination in this vulnerable population has not been confirmed. Although age is negatively correlated with serum immunoglobulin (Ig) levels, humoral responses to vaccination in elderly patients undergoing HD have not been investigated. To address this issue, we evaluated the anti-SARS-CoV-2 spike protein antibodies in nursing home residents on HD after BNT162b2 vaccine administration. Methods Patients on HD from a nursing home and care workers (controls) receiving two doses of the BNT162b2 vaccine between April and May 2021 were enrolled in this study. Those with a prior history of COVID-19 were excluded. Anti-spike protein antibodies were measured with the Elecsys (Roche) immunoassay system. Results The study included 26 nursing home residents (41% male;median age, 86 years) and 184 care workers (28% male;median age, 45 years). The median HD vintage was 51 months. After two doses of BNT162b2, 73% of the nursing home residents and 99.5% of the control group developed sufficient anti-spike protein antibodies (> 29 U/mL) to neutralize SARS-CoV-2. Three weeks after the second dose, median IgG titers of the residents and care workers were 83 [interquartile range (IQR) 17–511] and 1365 (IQR 847–2245) U/mL, respectively (p < 0.001). Conclusions The humoral response to BNT162b2 among elderly HD patients was relatively low;therefore, the optimal vaccination strategy for this population should be studied further to avoid COVID-19 outbreaks in healthcare facilities. Supplementary Information The online version contains supplementary material available at 10.1186/s41100-022-00397-5.

COVID-19 associated pulmonary aspergillosis: a nationwide survey by the Japanese Respiratory Society.

An online nationwide questionnaire survey in Japan revealed that the incidence rate of #COVID19 associated pulmonary aspergillosis in critical COVID-19 cases was extremely low (0.54%) compared with those previously reported in the USA and Europe https://bit.ly/2WdFtPj.

Empirical antibiotic usage and bacterial superinfections in patients with COVID-19 in Japan: A nationwide survey by the Japanese Respiratory Society.

An internet questionnaire survey for investigating empirical antibiotic usage and bacterial superinfections in patients with coronavirus disease-2019 (COVID-19) in Japan was conducted among the chief physicians of respiratory disease departments of 715 Japanese Respiratory Society-certified hospitals using Google Forms between January 28, 2021 and February 28, 2021. Responses to the questionnaire survey were obtained from 198 of 715 hospitals (27.6%). The survey revealed that the complication incidences of community-acquired pneumonia; hospital-acquired pneumonia, including ventilator-associated pneumonia; and sepsis were 2.86, 5.59, and 0.99%, respectively, among patients with moderate/severe and critical COVID-19. Bacterial co-infection and secondary infection rarely affected patients with COVID-19 in Japan, and the isolated pathogens were not specific to these patients. Moreover, the anti-inflammatory effects of macrolides for COVID-19 were not observed in several studies. These results might be useful in clinical practice for COVID-19.

Development and Evaluation of Quantitative Immunoglobulin G Enzyme-Linked Immunosorbent Assay for the Diagnosis of Coronavirus Disease 2019 Using Truncated Recombinant Nucleocapsid Protein as Assay Antigen.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Real-time RT-PCR is the most commonly used method for COVID-19 diagnosis. However, serological assays are urgently needed as complementary tools to RT-PCR. Hachim et al. 2020 and Burbelo et al. 2020 demonstrated that anti-nucleocapsid(N) SARS-CoV-2 antibodies are higher and appear earlier than the spike antibodies. Additionally, cross-reactive antibodies against N protein are more prevalent than those against spike protein. We developed a less cross-reactive immunoglobulin G (IgG) indirect ELISA by using a truncated recombinant SARS-CoV-2 N protein as assay antigen. A highly conserved region of coronaviruses N protein was deleted and the protein was prepared using an E. coli protein expression system. A total of 177 samples collected from COVID-19 suspected cases and 155 negative control sera collected during the pre-COVID-19 period were applied to evaluate the assay's performance, with the plaque reduction neutralization test and the commercial SARS-CoV-2 spike protein IgG ELISA as gold standards. The SARS-CoV-2 N truncated protein-based ELISA showed similar sensitivity (91.1% vs. 91.9%) and specificity (93.8% vs. 93.8%) between the PRNT and spike IgG ELISA, as well as also higher specificity compared to the full-length N protein (93.8% vs. 89.9%). Our ELISA can be used for the diagnosis and surveillance of COVID-19.

Discrepancy of SARS-CoV-2 PCR results due to the sample collection sites and possible improper sampling.

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5µL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity.

Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests.

INTRODUCTION: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital. METHODS: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses. RESULTS: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed. CONCLUSIONS: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.