Prolonged Symptoms after COVID-19 in Japan: A Nationwide Survey of the Symptoms and Their Impact on Patients' Quality of Life.

BACKGROUND: Clinical details of long COVID are still not well understood because of potential confounding with a wide range of pre-existing comorbidities. METHODS: The present study used datasets from a nationwide, cross-sectional, online survey. We determined which prolonged symptoms were more likely to be associated with post-COVID condition after adjusting for a wide range of comorbidities and baseline characteristics. This study also used the EuroQol 5 Dimension 5 Level (EQ-5D-5L) and Somatic Symptom Scale-8 to assess health-related quality of life (QOL) and somatic symptoms in individuals with a previous history of COVID-19, defined as the diagnosis of COVID-19 made at least 2 months prior to the online survey. RESULTS: In total, 19,784 respondents were included for analysis; of these, 2397 (12.1%) had a previous history of COVID-19. The absolute difference of adjusted prevalence of symptoms attributed to prolonged symptoms after COVID-19 ranged from -0.4% to +2.0%. Headache (adjusted odds ratio [aOR]: 1.22; 95% confidence interval [95% CI]:1.07-1.39), chest discomfort (aOR:1.34, 95% CI:1.01-1.77), dysgeusia (aOR: 2.05, 95% CI: 1.39-3.04), and dysosmia (aOR: 1.96, 95% CI: 1.35-2.84) were independently associated with a previous history of COVID-19. Individuals with a previous history of COVID-19 had lower health-related QOL scores. CONCLUSIONS: After adjusting for potential comorbidities and confounders, clinical symptoms, such as headache, chest discomfort, dysgeusia, and dysosmia, were found to be independently associated with a previous history of COVID-19, which was diagnosed 2 or more months previously. These protracted symptoms might have impacted QOL and the overall somatic symptom burden in subjects with a previous history of COVID-19.

Post-COVID Health-related Quality of Life and Somatic Symptoms: A National Survey in Japan

Background : The characteristics and risk factors of post-COVID-19 condition affecting health-related quality of life and the symptom burden are unclear. Methods : The present, cross-sectional study used the JASTIS (Japan Society and New Tobacco Internet Survey) database. EQ-5D-5L and Somatic Symptom Scale-8 were used to assess health-related quality of life and somatic symptoms, respectively. The participants were classified into a no-COVID-19, COVID-19 not requiring oxygen therapy or COVID-19 requiring oxygen therapy group. First, the entire cohort was analyzed. Then, sensitivity analysis was performed after excluding patients in the no-COVID-19 group with a history of close contact with individuals known to have the disease. Findings : In total, 30130 individuals (mean age: 47.8;females: 51.2%), including 539 and 805 with COVID-19 requiring and not requiring oxygen therapy, respectively, participated. The analysis of the entire cohort as well as the sensitivity analysis demonstrated that individuals with a history of COVID-19 had significantly lower EQ-5D-5L and significantly higher SSS-8 scores than those with no COVID-19 history. The group requiring oxygen therapy was associated with significantly lower EQ-5D-5L and higher SSS-8 scores than the group not requiring oxygen therapy. Propensity-score matching confirmed these results. Furthermore, two or more COVID-19 vaccinations were independently associated with high EQ-5D-5L and low SSS-8 scores (P < 0.001). Interpretation : The participants with a COVID-19 history, especially those with severe disease, had a significantly higher somatic symptom burden. Analysis after adjusting for potential confounders found that their quality-of-life was also severely affected. Vaccination is crucial to addressing these symptoms, especially in high-risk patients.

Analysis of hydroxychloroquine prescriptions for COVID-19 in Japan.

Number of hydroxychloroquine prescriptions per month for patients with coronavirus disease 2019 (COVID-19) in Japan from January 2020 to November 2021. The blue bars show the monthly number of chloroquine prescriptions for COVID-19 among patients in the Medical Data Vision database, which includes data on approximately 20% of acute care hospitals in Japan. The gray line shows the national number of COVID-19 notifications in Japan by month over the same period.

Modelling of salt intake reduction by incorporation of umami substances into Japanese foods: a cross-sectional study.

BACKGROUND: Evidence has demonstrated that excess sodium intake is associated with development of several non-communicable diseases. The main source of sodium is salt. Therefore, reducing salt intake in foods is an important global public health effort to achieve sodium reduction and improve health. This study aimed to model salt intake reduction with 'umami' substances among Japanese adults. The umami substances considered in this study include glutamate or monosodium glutamates (MSG), calcium diglutamate (CDG), inosinate, and guanylate. METHODS: A total of 21,805 participants aged 57.8 years on average from the National Health and Nutrition Survey was used in the analysis. First, we employed a multivariable linear regression approach with overall salt intake (g/day) as a dependent variable, adjusting for food items and other covariates to estimate the contribution of salt intake from each food item that was selected through an extensive literature review. Assuming the participants already consume low-sodium products, we considered three scenarios in which salt intake could be reduced with the additional umami substances up to 30%, 60% and 100%. We estimated the total amount of population-level salt reduction for each scenario by age and gender. Under the 100% scenario, the Japan's achievement rates against the national and global salt intake reduction goals were also calculated. RESULTS: Without compromising the taste, the 100% or universal incorporation of umami substances into food items reduced the salt intake of Japanese adults by 12.8-22.3% at the population-level average, which is equivalent to 1.27-2.22 g of salt reduction. The universal incorporation of umami substances into food items changed daily mean salt intake of the total population from 9.95 g to 7.73 g: 10.83 g to 8.40 g for men and 9.21 g to 7.17 g for women, respectively. This study suggested that approximately 60% of Japanese adults could achieve the national dietary goal of 8 g/day, while only 7.6% would meet the global recommendation of 5.0 g/day. CONCLUSIONS: Our study provides essential information on the potential salt reduction with umami substances. The universal incorporation of umami substances into food items would enable the Japanese to achieve the national dietary goal. However, the reduced salt intake level still falls short of the global dietary recommendation.

Serious mental illness and in-hospital mortality among hospitalized patients with acute COVID-19: A large-database analysis in Japan

Objective The association of serious mental illness (affective or non-affective psychotic disorders) with higher mortality in patients infected with acute coronavirus disease 2019 (COVID-19) has been suggested. Although this association remains significant after adjusting for medical comorbidities in previous studies, admission clinical status and treatment modalities should be considered as important confounding factors. Methods We aimed to assess whether serious mental illness is associated with in-hospital mortality, in patients with COVID-19 by adjusting for comorbidities, admission clinical status, and treatment modalities. Our nationwide cohort in Japan included consecutive patients admitted to 438 acute care hospitals for laboratory-confirmed acute COVID-19 from January 1, 2020 to November 30, 2021. Results Of 67,348 hospitalized patients (mean [standard deviation] age, 54 [18.6] years;3891 [53.0%] female), 2524 patients (3.75%) had serious mental illness. In-hospital mortality was 282/2524 (11.17%) among patients with serious mental illness, while it was 2118/64,824 (3.27%) in other patients. In the fully adjusted model, serious mental illness was significantly associated with in-hospital mortality (odds ratio, 1.49;95% CI, 1.27–1.72). E-value analysis confirmed the robustness of the results. Conclusion Serious mental illness remains a risk for mortality in acute COVID-19 after adjusting for comorbidities, admission clinical status, and treatment modalities. Vaccination, diagnosis, early assessment and treatment should be prioritized for this vulnerable group.

Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study.

BACKGROUND: Steroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias. METHODS: We performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020-2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy. RESULTS: During the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52-0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02-3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40-250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71-0.89). CONCLUSION: The results of our study suggest that intravenous methylprednisolone showed dose-response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Serious mental illness and in-hospital mortality among hospitalized patients with acute COVID-19: A large-database analysis in Japan.

OBJECTIVE: The association of serious mental illness (affective or non-affective psychotic disorders) with higher mortality in patients infected with acute coronavirus disease 2019 (COVID-19) has been suggested. Although this association remains significant after adjusting for medical comorbidities in previous studies, admission clinical status and treatment modalities should be considered as important confounding factors. METHODS: We aimed to assess whether serious mental illness is associated with in-hospital mortality, in patients with COVID-19 by adjusting for comorbidities, admission clinical status, and treatment modalities. Our nationwide cohort in Japan included consecutive patients admitted to 438 acute care hospitals for laboratory-confirmed acute COVID-19 from January 1, 2020 to November 30, 2021. RESULTS: Of 67,348 hospitalized patients (mean [standard deviation] age, 54 [18.6] years; 3891 [53.0%] female), 2524 patients (3.75%) had serious mental illness. In-hospital mortality was 282/2524 (11.17%) among patients with serious mental illness, while it was 2118/64,824 (3.27%) in other patients. In the fully adjusted model, serious mental illness was significantly associated with in-hospital mortality (odds ratio, 1.49; 95% CI, 1.27-1.72). E-value analysis confirmed the robustness of the results. CONCLUSION: Serious mental illness remains a risk for mortality in acute COVID-19 after adjusting for comorbidities, admission clinical status, and treatment modalities. Vaccination, diagnosis, early assessment and treatment should be prioritized for this vulnerable group.

Antibody and T-Cell Responses against SARS-CoV-2 after Booster Vaccination in Patients on Dialysis: A Prospective Observational Study.

Intensive vaccination is recommended for populations more vulnerable to COVID-19 infection, although data regarding the built of immunity after vaccination for dialysis patients are lacking. This prospective, observational cohort study of maintenance hemodialysis patients examined IgG antibody levels against the SARS-CoV-2 spike (S1) protein, neutralizing activity, and interferon gamma levels after the third dose of the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Humoral immunity was repeatedly measured for up to two months. The study includes 58 patients on hemodialysis. Median neutralizing antibodies reached a maximum at 56 and 9 days after booster vaccination with BNT162b2 and mRNA-1273, respectively. The median IgG antibody titer reached a maximum of 3104.38 and 7209.13 AU/mL after 16 days of booster dose, and cellular immunity was positive in 61.9% and 100% of patients with BNT162b2 and mRNA-1273 vaccination, respectively. By repeating the measurements over a period of two months, we clarified the chronological aspects of the acquisition of humoral immunity in dialysis patients after a booster COVID-19 vaccination; most dialysis patients acquired not only humoral immunity, but also cellular immunity against SARS-CoV-2. Future research should investigate the continued long-term dynamics of antibody titers and cellular immunity after the third or further vaccinations, evaluating the need for additional vaccinations for hemodialysis patients.

Association between hospital internal medicine physician workforce and patient admissions during the COVID-19 pandemic in Japan.

BACKGROUND: Hospital physician workforce in Japan is the lowest among developed countries. Many patients with novel coronavirus disease 2019 (COVID-19) with high risk of mortality could not be hospitalized during case surges in Japan and only about 5% of total acute care beds were used as COVID-19 beds nationwide. However, the relationship between the number of hospital physicians and patient admissions remains unclear. Thus, we aimed to evaluate this relationship in areas with the highest incidences during the surges. METHODS: Data collection was performed for teaching hospitals accredited with the specialty of internal medicine in three prefectures which experienced the highest COVID-19 incidences in Japan (Tokyo, Osaka, Okinawa). Association was examined between the number of full-time physicians (internal medicine staff physicians and residents) and admissions of internal medicine patients through ambulance transport from April 2020 to March 2021. Analysis was conducted separately for community hospitals and university hospitals because the latter have roles as research institutions in Japan. Community hospitals included private, public, and semi-public hospitals. RESULTS: Of 117 teaching hospitals in three prefectures, data from 108 teaching hospitals (83 community hospitals and 25 university hospitals) were available. A total of 102,400 internal medicine patients were admitted to these hospitals during the one-year period. Private hospitals received the greatest mean number of patient admissions (290 per 100 beds), followed by public hospitals (227) and semi-public hospitals (201), and university hospitals (94). Among community hospitals, a higher number of resident physicians per 100 beds was significantly associated with a greater number of patient admissions per 100 beds with beta coefficient of 11.6 (95% CI, 1.5 to 21.2, p = 0.025) admissions by one physician increase per 100 beds. There was no such association among university hospitals. CONCLUSIONS: Community hospitals with many resident physicians accepted more internal medicine admissions through ambulance transport during the COVID-19 pandemic. An effective policy to counter physician shortage in hospitals in Japan may be to increase internal medicine resident physicians among community hospitals to save more lives.

Prevalence of Asymptomatic SARS-CoV-2 Infection in Japan.

Importance: Real-world evidence of SARS-CoV-2 transmission is needed to understand the prevalence of infection in the Japanese population. Objective: To conduct sentinel screening of the Japanese population to determine the prevalence of SARS-CoV-2 infection in asymptomatic individuals, with complementary analysis for symptomatic patients as reported by active epidemiologic surveillance used by the government. Design, Setting, and Participants: This cross-sectional study of a sentinel screening program investigated approximately 1 million asymptomatic individuals with polymerase chain reaction (PCR) testing for SARS-CoV-2 infection between February 22 and December 8, 2021. Participants included children, students, employed adults, and older individuals, as well as volunteers to broadly reflect the general Japanese population in the 14 prefectures of Japan that declared a state of emergency. Saliva samples and a cycle threshold (Ct) value of approximately 40 as standard in Japan were used. Polymerase chain reaction testing for symptomatic patients was separately done by public health authorities, and the results were obtained from the Ministry of Health, Labour, and Welfare of Japan to complement data on asymptomatic infections from the present study. Main Outcomes and Measures: Temporal trends in positivity and prevalence (including surges of different variants) and demographic associations (eg, age, geographic location, and vaccination status) were assessed. Results: The positive rate of SARS-CoV-2 infection in 1 082 976 asymptomatic individuals (52.08% males; mean [SD] age 39.4 [15.7] years) was 0.03% (95% CI, 0.02%-0.05%) during periods without surges and a maximum of 0.33% (95% CI, 0.25%-0.43%) during peak surges at the Japanese standard Ct value of approximately 40; however, the positive rate would have been 10-fold less at a Ct value of 25 as used elsewhere in the world (eg, UK). There was an increase in patients with a positive PCR test result with a Ct value of 25 or 30 preceding surges in infection and hotspots of asymptomatic infections. Conclusions and Relevance: In this cross-sectional study of asymptomatic SARS-CoV-2 infection in the general population of Japan in 2021, as investigated by sentinel surveillance, a low rate of infection was seen in the Japanese population compared with reported levels elsewhere in the world. This finding provides real-world data on the state of infection in Japan.

Prevalence and characteristics of antibiotic prescription for acute COVID-19 patients in Japan.

COVID-19 is a viral infection and does not require antibiotics. The study aimed to elucidate a prescribing pattern of antibiotics for COVID-19. A nationwide cross-sectional study was conducted in Japan. The Diagnosis and Procedure Combinations (DPC) data was used to collect information, covering 25% of all acute care hospitals in the country. In 140,439 COVID-19 patients, 18,550 (13.21%) patients received antibiotics. Antibiotics were prescribed more often in inpatients (10,809 out of 66,912, 16.15%) than outpatients (7741 out of 73,527, 10.53%) (p < 0.001). Outpatient prescription was significantly associated with older patients (odds ratio [OR], 4.66; 95% confidence interval [CI] 4.41-4.93) and a greater Charlson index (OR with one-point index increase, 1.22; 95% CI 1.21-1.23). Inpatient prescription was significantly associated with older patients (OR 2.10; 95% CI 2.01-2.21), male gender (OR 1.12, 95% CI 1.07-1.18), a greater Charlson index (OR with one-point increase, 1.06; 95% CI 1.05-1.07), requirement of oxygen therapy (OR 3.44; 95% CI 3.28-3.60) and mechanical ventilation (OR 15.09; 95% CI 13.60-16.74). The most frequently prescribed antibiotic among outpatients was cefazolin, while that among inpatients was ceftriaxone. Antibiotic prescription is relatively low for acute COVID-19 in Japan. Antibiotic prescription was associated with older age, multi-morbidity, severe disease, and winter season.

Effectiveness of the Booster of SARS-CoV-2 Vaccine among Japanese Adolescents: A Cohort Study.

Vaccination is effective in preventing COVID-19-related hospitalization among all age groups, but there is limited evidence on the effectiveness of the booster of the SARS-CoV-2 vaccine among adolescents. We analyzed the data on the status of SARS-CoV-2 infection and their vaccination profiles in adolescents aged 13-18 years in Soma city (Fukushima, Japan) (n = 1835) from 14 May to 15 June 2022. The crude incidence rate and 95% confidence interval were calculated with the negative-binomial regression model after classifying the immunization status. The crude effectiveness of a booster administration to prevent infections was estimated as 86.4% (95% confidence interval: 57.2-95.7) when compared with the primary vaccination alone. The results of this study support that the community-based mass vaccination campaign of a booster dose among adolescents has additional protection from COVID-19 during the period of the B.1.1.529 (omicron) variant wave.

Humoral response to SARS-CoV-2 vaccination in haemodialysis patients and a matched cohort.

OBJECTIVES: SARS-CoV-2 vaccination is a crucial intervention for infection control; however, the immune response to vaccination in dialysis patients has been reported to be moderate compared with healthy adults. There are few studies available on humoral response in immunised dialysis patients compared with well-matched control group, we conducted a prospective cohort study measuring SARS-CoV-2 antibody titres in Fukushima Prefecture, Japan since September 2021. PARTICIPANTS: We compared the titres of both anti-SARS-CoV-2 S1 IgG and neutralising antibodies of 65 haemodialysis patients (dialysis group) with 500 residents in Soma, Fukushima (control group). METHODS: Coarsened exact matching was used to balance sex, age and days from the second dose between dialysis and control groups. RESULTS: Significant differences in the titres of anti-SARS-CoV-2 S1 IgG and neutralising antibodies were observed between the dialysis and control groups; anti-SARS-CoV-2 S1 IgG: 168.35 (4.48-1074.29) AU/mL and 269.81 (4.72-945.96) AU/mL in dialysis and control groups, p=0.02, neutralising antibodies: 35.77 (2.94-826.06) AU/mL and 62.22 (0.00-535.57) AU/mL, p=0.007, respectively). CONCLUSIONS: We observed significantly reduced anti-SARS-CoV-2 S1 antibody and neutralising antibodies in haemodialysis patients compared with cohorts matched for duration after vaccination. Patients receiving haemodialysis should be carefully monitored for immunological responses to the vaccination and COVID-19 infection.

Humoral immunity after second dose of BNT162b2 vaccine in Japanese communities: an observational cross-sectional study, Fukushima Vaccination Community Survey.

To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort. METHODS: Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained. RESULTS: Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities. CONCLUSIONS: Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy.

Effect of the Tokyo 2020 Summer Olympic Games on COVID-19 incidence in Japan: a synthetic control approach.

BACKGROUND: The Tokyo 2020 Summer Olympic Games (23 July-8 August 2021) were held in the middle of Japan's fifth wave of COVID-19, when the number of cases was on the rise, and coincided with the fourth state of emergency implemented by the host city, Tokyo. AIM: This study aimed to assess whether the hosting of the Games was associated with a change in the number of COVID-19 cases in Japan using a synthetic control method. METHODS: A weighted average of control countries with a variety of predictors was used to estimate the counterfactual trajectory of daily COVID-19 cases per 1 000 000 population in the absence of the Games in Japan. Outcome and predictor data were extracted using official and open sources spanning several countries. The predictors comprise the most recent country-level annual or daily data accessible during the Games, including the stringency of the government's COVID-19 response, testing capacity and vaccination capacity; human mobility index; electoral democracy index and demographic, socioeconomic, health and weather information. After excluding countries with missing data, 42 countries were ultimately used as control countries. RESULTS: The number of observed cases per 1 000 000 population on the last day of the Games was 109.2 (7-day average), which was 115.7% higher than the counterfactual trajectory comprising 51.0 confirmed cases per 1 000 000 population. During the Olympic period (since 23 July), the observed cumulative number of cases was 61.0% higher than the counterfactual trajectory, comprising 143 072 and 89 210 confirmed cases (p=0.023), respectively. The counterfactual trajectory lagged 10 days behind the observed trends. CONCLUSIONS: Given the increasing likelihood that new emerging infectious diseases will be reported in the future, we believe that the results of this study should serve as a sentinel warning for upcoming mega-events during COVID-19 and future pandemics.

Designing isolation guidelines for COVID-19 patients with rapid antigen tests.

Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adopted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation, whereas others may still be infectious. Utilizing viral test results to determine isolation length would minimize both the risk of prematurely ending isolation of infectious patients and the unnecessary individual burden of redundant isolation of noninfectious patients. In this study, we develop a data-driven computational framework to compute the population-level risk and the burden of different isolation guidelines with rapid antigen tests (i.e., lateral flow tests). Here, we show that when the detection limit is higher than the infectiousness threshold values, additional consecutive negative results are needed to ascertain infectiousness status. Further, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation.

Estimation of timing of infection from longitudinal SARS-CoV-2 viral load data: mathematical modelling study

Multiple waves of the COVID-19 epidemic have hit most countries by the end of 2021. Most of those waves are caused by emergence and importation of new variants. To prevent importation of new variants, combination of border control and contact tracing is essential. However, the timing of infection inferred by interview is influenced by recall bias and hinders the contact tracing process. We propose a novel approach to infer the timing of infection, by employing a within-host model to capture viral load dynamics after the onset of symptoms. We applied this approach to ascertain secondary transmission which can trigger outbreaks. As a demonstration, the 12 initial reported cases in Singapore, which were considered as imported because of their recent travel history to Wuhan, were analyzed to assess whether they are truly imported. Our approach suggested that 6 cases were infected prior to the arrival in Singapore, whereas other 6 cases might have been secondary local infection. Three among the 6 potential secondary transmission cases revealed that they had contact history to previously confirmed cases. Contact trace combined with our approach using viral load data could be the key to mitigate the risk of importation of new variants by identifying cases as early as possible and inferring the timing of infection with high accuracy.