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We investigated changes in heterotrophic bacterial metabolic activities and associated carbon cycles in response to a change in dominant phytoplankton communities during two contrasting environmental conditions in austral summer in the Amundsen Sea polynya (ASP), Antarctica: the closed polynya condition in 2014 (ANA04) and the open polynya condition in 2016 (ANA06). In ANA04, Phaeocystis antarctica predominated phytoplankton biomass, comprising 78% of total phytoplankton carbon biomass, whereas diatoms and Dictyocha speculum accounted for 45% and 48% of total phytoplankton carbon biomass, respectively, in ANA06. Bacterial production (BP) showed a significant positive correlation with only chlorophyll-a (Chl-a, rho = 0.66, p < 0.001) in P. antarctica-dominated ANA04, whereas there were significant positive relationships of BP with various organic carbon pools, such as chromophoric dissolved organic matter (CDOM, rho = 0.84, p < 0.001), Chl-a (rho = 0.59, p < 0.001), and dissolved organic carbon (DOC, rho = 0.51, p = 0.001), in ANA06 when diatoms and D. speculum co-dominated. These results indicate that BP depended more on DOC directly released from P. antarctica in ANA04, but was supported by DOC derived from various food web processes in the diatom-dominated system in ANA06. The BP to primary production (BP : PP) ratio was three-fold higher in P. antarctica-dominated ANA04 (BP: PP = 0.09), than in diatom- and D. speculum-co-dominated ANA06 (BP : PP = 0.03). These results suggested that the microbial loop is more significant in Phaeocystis-dominated conditions than in diatom-dominated conditions. In addition, the decreases in BP : PP ratio and bacterial respiration with increasing diatom proportion in the surface mixed layer indicated that the change from P. antarctica to diatom predominance enhanced biological carbon pump function by increasing particulate organic carbon export efficiency. Consequently, our results suggest that bacterial metabolic response to shifts in phytoplankton communities could ultimately affect larger-scale ecological and biogeochemical processes in the water column of the ASP.

We characterized the biogeochemical organic carbon (Corg) cycles in the surface sediment layer of the Ulleung Basin (UB) of the East Sea. The total oxygen uptake (TOU) rate and the diffusive oxygen uptake (DOU) rate of the sediment were measured using an autonomous in situ benthic lander equipped with a benthic chamber (KIOST BelcII) and a microprofiler (KIOST BelpII). The TOU rate was in the range of 1.51 to 1.93 mmol O2 m−2 d−1, about double the DOU rate. The high TOU/DOU ratio implies that the benthic biological activity in the upper sediment layer is one of the important factors controlling benthic remineralization. The in situ oxygen exposure time was about 20 days, which is comparable to the values of other continental margin sediments. The sedimentary Corg oxidation rates ranged from 6.4 to 6.5 g C m−2 yr−1, which accounted for ~2% of the primary production in UB. The Corg burial fluxes ranged from 3.14 ± 0.12 to 3.48 ± 0.60 g C m−2 yr−1, corresponding to more than 30% of the deposited Corg buried into the inactive sediment deep layer.

This study aims to evaluate the effect of androgen-deprivation therapy (ADT) on the incidence of dementia, after considering the time-dependent survival in patients with prostate cancer (PC) using a Korean population-based cancer registry database. After excluding patients with cerebrovascular disease and dementia before or within the 3-month-ADT and those with surgical castration, 9880 (19.3%) patients were matched into ADT and non-ADT groups using propensity-score matching (PSM) among 51,206 patients registered between 2006 and 2013. To define the significant relationship between ADT duration and the incidence of dementia, the extension Cox proportional hazard model was used with p-values < 0.05 regarded as statistically significant. The mean age and survival time were 67.3 years and 4.33 (standard deviation [SD] 2.16) years, respectively. A total of 2945 (9.3%) patients developed dementia during the study period, including Parkinson’s (11.0%), Alzheimer’s (42.6%), vascular (18.2%), and other types of dementia (28.2%). Despite PSM, the PC-treatment subtypes, survival rate, and incidence of dementia significantly differed between the ADT and non-ADT groups (p < 0.05), whereas the rate of each dementia subtype did not significantly differ (p = 0.069). A multivariate analysis for dementia incidence showed no significance of ADT type or use duration among patients with PC (p > 0.05), whereas old age, obesity, regional SEER stage, a history of cerebrovascular disease, and a high Charlson Comorbidity Index were significant factors for dementia (p < 0.05). Insignificant correlation was observed between ADT and the incidence of dementia based on the extension survival model with PSM among patients with PC.

BackgroundIsolation of COVID-19 patients is a crucial infection control measure to prevent further SARS-CoV-2 transmission, but determining an appropriate timing to end the COVID-19 isolation is a challenging. We evaluated the performance of the self-test rapid antigen test (RAT) as a potential proxy to terminate the isolation of COVID-19 patients.Materials and methodsSymptomatic COVID-19 patients were enrolled who were admitted to a regional community treatment center (CTC) in Seoul (South Korea). Self-test RAT and the collection of saliva samples were performed by the patients, on a daily basis, until patient discharge. Cell culture and subgenomic RNA detection were performed on saliva samples.ResultsA total of 138 pairs of saliva samples and corresponding RAT results were collected from 34 COVID-19 patients. Positivity of RAT and cell culture was 27% (37/138) and 12% (16/138), respectively. Of the 16 culture-positive saliva samples, seven (43.8%) corresponding RAT results were positive. Using cell culture as the reference standard, the overall percent agreement, percent positive agreement, and percent negative agreement of RAT were 71% (95% CI, 63–78), 26% (95% CI, 12–42), and 82% (95% CI, 76–87), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the RAT for predicting culture results were 44% (95% CI, 20–70), 75% (95% CI, 66–82), 18% (95% CI, 8–34), and 91% (95% CI, 84–96), respectively.ConclusionAbout half of the patients who were SARS-CoV-2 positive based upon cell culture results gave negative RAT results. However, the remaining positive culture cases were detected by RAT, and RAT showed relatively high negative predictive value for viable viral shedding.

Metasurface-based microdisplays Organic light-emitting diodes (OLEDs) have found wide application in high-resolution, large-area televisions and the handheld displays of smartphones and tablets. With the screen located some distance from the eye, the typical number of pixels per inch is in the region of hundreds. For near-eye microdisplays—for example, in virtual and augmented reality applications—the required pixel density runs to several thousand pixels per inch and cannot be met by present display technologies. Joo et al. developed a full-color, high-brightness OLED design based on an engineered metasurface as a tunable back-reflector. An ultrahigh density of 10,000 pixels per inch readily meets the requirements for the next-generation microdisplays that can be fabricated on glasses or contact lenses. Science , this issue p. 459

Coronavirus disease 2019 (COVID‐19) is a novel infectious disease that continues to spread on a global scale. There has been growing concern about donor‐derived transmissions of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Herein, we present the case of a patient who underwent ABO‐incompatible living donor liver transplantation without knowing that the liver donor was infected with COVID‐19 during the donation procedure. In this case, the donor‐derived transmission to the recipient was not identified, and the liver donor was found to be recovering from a COVID‐19 infection. The donor‐derived transmission was not identified.

The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription–PCR. Anti–SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ–induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5–10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.

We performed retrospective study to identify the characteristics of invasive Trichosporon asahii infection. A total of 102 patients with T. asahii were identified including 18 (18%) with invasive infection. Invasive infection was associated with indwelling central venous catheter (94% vs 54%, P = .001), prior antifungal agent use (50% vs 18%, P = .01), hematologic malignancy (33% vs 7%, P = .006), and end-stage renal disease (28% vs 7%, P = .02). Patients with invasive infections had higher in-hospital mortality than patients with noninvasive infections (61% vs 27%, P = .006). Those with the above risk factors should be monitored for the development of invasive T. asahii infection.Lay summaryPatients with indwelling central venous catheter, prior antifungal agent use, hematologic malignancy, and end-stage renal disease were associated with invasive Trichosporon asahii infection. Patients with invasive infections had higher in-hospital mortality than patients without invasive infection.

We evaluated the effectiveness of IGRA-based isoniazid (INH) treatment with the diagnostic value of quantitative IGRA titer for post-transplant tuberculosis (TB) in kidney transplant (KT) recipients.All adult KT recipients were enrolled from January 2014 to December 2017. The development of TB after KT was observed, stratified by quantitative IGRA results as well as by IGRA results with/without INH treatment.Of 1150 KT recipients, 322 (28%) revealed positive IGRA results (≥0.35 IU/mL) and 12 (1.0%) developed TB. Seven (3.2%) of 217 patients with positive IGRA without INH developed TB, whereas none of 105 patients with positive IGRA with INH developed TB (rate difference -1616 per 100,000 person-years, P = 0.016) and 5 (0.6%) of 828 patients with negative or indeterminate IGRA developed TB (rate difference -1388 per 100,000 person-years, P0.001). Among the 217 positive IGRA patients without INH, 6 (6.4%) of 94 patients who had positive IGRA titer2.96 IU/mL developed TB, whereas one (0.8%) of 123 patients who had positive IGRA titer≤2.96 IU/mL developed TB (rate difference 2964 per 100,000 person-years, P = 0.017).IGRA-based INH treatment with risk stratification by quantitative IGRA results appears to be effective to prevent the development of TB in KT recipients.

Data regarding extraintestinal Clostridioides difficile infections (ECDIs) remain scarce and anecdotal. We conducted a retrospective cohort study to investigate characteristics and prognostic factors in patients with ECDI. From January 1997 through December 2018, 60 patients were enrolled and divided into three groups as follows: group A (gastrointestinal [GI] disruption caused by malignancy, n = 13); group B (GI disruption from causes other than malignancy, n = 25); group C (no GI disruption, n = 22). GI disruption was defined as compromised integrity of the GI tract caused by abdominal surgery, perforation, malignancy, enterocolitis, or bleeding. The incidence of ECDI was 2.53 per 100,000 admissions. The most common specimens yielded C. difficile were blood (36.7%), peritoneal fluid (20.0%), and abscesses (16.7%). Six patients (10.0%) had confirmed C. difficile enterocolitis, and 36 patients (60.0%) had a polymicrobial infection. C. difficile bacteremia was significantly more common in group A patients than those in groups B or C (53.8% vs. 48.0% vs. 13.6%, p = 0.02), as was the 30-day mortality rate (69.2% vs. 12.0% vs. 18.2%, respectively; p 0.001). In multivariate analysis, group A (adjusted odds ratio [aOR], 17.32; 95% confidence interval [CI], 2.96-101.21; p = 0.002) and an age of 65 years (aOR, 7.09; 95% CI, 1.31-38.45; p = 0.02) were independent risk factors for 30-day mortality. ECDI was uncommonly associated with C. difficile enterocolitis. Two factors, GI disruption caused by malignancy, and old age, were associated with significantly poorer short-term outcomes.

We investigated the association between herpes zoster (HZ) and dementia, and the effects of antiviral therapy on the risk of dementia. We used the National Health Insurance Service-National Sample Cohort in South Korea to identify individuals that were followed from January 1, 2002, to December 31, 2013. Occurrences of HZ and dementia were identified using the relevant diagnostic codes. Dementia was defined as the presence of diagnostic codes and history of anti-dementia drug prescription. Propensity score matching (1:1) was carried out among HZ patients according to antiviral therapy. A total of 229,594 individuals aged ≥50 years were analyzed. The incidences of the first-diagnosed HZ and dementia were 16.69 and 4.67 per 1000 person-years (PY), respectively. HZ patients had a higher risk of dementia (incidence rate ratio [IRR], 1.94 [95% CI 1.83–2.06]; adjusted hazard ratio [HR], 1.12 [95% CI 1.05–1.19]). Of the 34,505 patients with HZ, 28,873 (84%) had received antiviral treatment. The crude incidence rates of subsequent dementia in the treated and untreated groups were 7.79 and 12.27 per 1000 PY, respectively, resulting in an IRR of 0.64 (95% CI 0.56–0.72) and covariate-adjusted HR of 0.79 (95% CI 0.69–0.90). After propensity score matching, the treated group showed a significantly lower risk of dementia (HR 0.76; 95% CI 0.65–0.90). In this large population-based cohort study, HZ was associated with a higher risk of dementia. The use of antiviral agents in HZ patients was associated with lower risks of dementia.

Purpose This study aimed to examine the causes of death in Korean patients who underwent radical prostatectomy for prostate cancer and investigate the relationship between comorbidity and mortality. Materials and methods We conducted a retrospective multicenter cohort study including 4,064 consecutive patients who had prostate cancer and underwent radical prostatectomy between January 1998 and June 2013. The primary endpoint of this study was all-cause mortality, and the secondary endpoints were cancer-specific mortality (CSM) and other-cause mortality (OCM). Charlson comorbidity index (CCI) was calculated to assess the comorbidities of each patient. Results Of 4,064 patients, 446 (11.0%) died during follow-up. The cause of death was prostate cancer in 132 patients (29.6%), other cancers in 121 patients (27.1%), and vascular disease in 57 patients (12.8%) in our cohort. The overall 10-year CSM rate was lower than the OCM rate (4.6% vs. 10.5%). The 10-year CSM rate was lower than the OCM rate in low- to intermediate-risk group patients (1.2% vs. 10.6%), whereas they were similar in high-risk group patients (11.8% vs. 10.1%). In the multivariable analysis, CCI was independently associated with all-cause mortality after radical prostatectomy, regardless of age and pathologic features. Conclusion Death from prostate cancer was rare in Korean men who underwent radical prostatectomy. Clinicians should be aware of the possibility of overtreatment of low-risk prostate cancer in men with significant comorbidity. Our findings may help to facilitate counseling and plan management in this patient group.

The clinical implications of postoperative detection of circulating tumor cells in prostate cancer are largely unknown. We investigated the association between postoperative circulating tumor cell detection after radical prostatectomy and disease recurrence in prospectively enrolled patients with prostate cancer.A total of 203 patients with an undetectable prostate specific antigen who had undergone radical prostatectomy for prostate cancer were prospectively enrolled. Circulating tumor cell sampling was performed at a median of 4.5 months after surgery. The primary end point was biochemical recurrence-free survival. Detection of circulating tumor cells in the blood of patients was performed using a novel approach with a replication-competent adenovirus controlled by prostate specific antigen/prostate specific membrane antigen transcription regulatory elements (Ad5/35E1aPSESE4).Circulating tumor cells were detected in 73 (36.0%) patients with undetectable prostate specific antigen concentrations after surgery. The 3-year biochemical recurrence-free survival rate from the time of surgery was significantly higher in circulating tumor cell-negative than in circulating tumor cell-positive cases (81.6% vs 48.9%, log rank p0.001). Multivariable analysis showed that postoperative circulating tumor cell detection was independently associated with an increased risk of biochemical recurrence (HR 5.42, 95% CI 3.24-9.06, p0.001). C-index was increased in combinations of multivariable model and postoperative circulating tumor cell detection compared with the multivariable model alone.Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future.

Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0–2), moderate (3–5), and high risk (6–8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p

Background Pulmonary mucormycosis (PM) represents a serious burden in terms of morbidity and mortality in immunocompromised patients. Studies of prognostic factors in patients with PM are limited and have involved small numbers of patients. Methods Adult patients diagnosed with proven and probable PM according to the modified definitions of the EORTC/MSG 2008 in a tertiary hospital in Seoul, South Korea, between 2008 and 2019 were retrospectively enrolled. Results A total of 49 patients including 31 (63%) with proven PM and 18 (37%) with probable PM were enrolled. The 90-day mortality rate was 49% (24/49). Neutropenia, thrombocytopenia, use of voriconazole at clinical suspicion, positivity of non-sterile culture, use of steroid and treatment without surgery were more common in fatal cases than non-fatal cases. Voriconazole use at clinical suspicion for invasive mould pneumonia (OR 6.91, P = .01) and prolonged neutropenia (OR 4.86, P = .03) were independent risk factors for mortality. Voriconazole use at clinical suspicion was associated with positive galactomannan (GM) assay (OR 5.93, P = .02) and history of invasive pulmonary aspergillosis (OR, 6.88, P = .05). Conclusion About half of the patients with PM died within 90 days of diagnosis, and fatal outcomes were common in patients with prolonged neutropenia and empirical voriconazole use. Caution is needed in using voriconazole even in patients with positive GM results and prior histories of invasive pulmonary aspergillosis in whom PM cannot be ruled out by differential diagnosis.

We investigated the effects of Manila clam aquaculture on the rates and pathways of anaerobic organic carbon (OC) oxidation in highly bioturbated (HB) and poorly bioturbated (PB) sediment in Keunso Bay, Yellow Sea. Due to the labile organic matter supply via sediment reworking by Manila clams, the anaerobic OC oxidation rate in HB sediment (38.8 mmol m-2 d-1) was ~1.5 times higher than that in PB sediment (26.8 mmol m-2 d-1). Microbial Fe(III) reduction (FeR) dominated OC oxidation pathways in HB sediment, comprising 55 to 76% of anaerobic OC oxidation, whereas sulfate reduction (SR) was the dominant oxidation pathway in PB sediment, accounting for up to 92% of anaerobic OC oxidation. Despite higher anaerobic respiration rates at the HB site, concentrations of NH4+, PO43-, oxalate-extractable iron (Fe(II)(oxal)), and total reduced inorganic sulfur were 2 to 3 times lower in HB than in PB sediment. Conversely, the concentration of reactive Fe(III)(oxal) at the HB site (2243 mmol m-2) exceeded that at the PB site (1127 mmol m-2) by a factor of 2. These results indicate that bioturbation by Manila clams enhances the re-oxidation processes of reduced metabolites in the sediment, thereby prohibiting SR and promoting FeR. Overall, the results suggest that aquaculture activities of Manila clams shift the dominant OC oxidation pathways in sediment from SR to FeR, which generates relatively oxidized and less sulfidic environments.

Background/Aims: We evaluated the usefulness in kidney transplant (KT) candidates of cytomegalovirus (CMV)-specific enzyme-linked immunospot (ELISPOT) assays for predicting the development of post-transplant CMV infections. Methods: All adult recipients admitted for living-donor KT between March 2014 and March 2015 were prospectively enrolled except donor CMV-seropositive and recipient seronegative (D+/R-) recipients. All the enrolled patients underwent CMV-specific ELISPOT assays before transplant, and a researcher blinded to the results of these assays examined the patients for CMV infection at least 6 months post-transplant. Results: Of 133 KT recipients, 44 (33%) developed CMV infections. When we used the cut-off determined by receiver operator characteristic curve, 16 of the 34 patients (47%) with negative pp65-specific ELISPOT results (< 11 spots/200,000 cells) developed CMV infections, whereas 28 of the 99 patients (39%) with positive pp65-specific ELISPOT results at baseline (≥ 11 spots/200,000 cells) developed CMV infections after KT (p = 0.02). Based on the multivariable Cox regression model, negative pp65-specific ELISPOT assay results was an independent risk factor for CMV infection (adjusted hazard ratio [AHR], 1.87; 95% confidence interval [CI], 1.01 to 3.46; p = 0.047) as well as age (AHR, 1.05; 95% CI, 1.01 to 1.08; p = 0.007). Conclusions: Pre-transplant CMV-specific ELISPOT assay appears to predict the development of CMV infections after KT in recipients at moderate risk such as CMV-seropositive recipients (Clinical Trial Registration Number NCT 02025335).

Background: Due to the low sensitivity of mould culture, clinicians usually depend on the histomorphologic diagnosis of invasive mould infection for empirical antifungal therapy. However, definite diagnosis is not always possible based on the mould morphology. We thus compared the histomorphologic diagnosis with immunohistochemistry (IHC)- and culture-based diagnosis.Methods: All adult patients who underwent tissue biopsy and in whom the histomorphologic diagnosis revealed invasive mould infection were enrolled at a tertiary hospital, Seoul, South Korea, between 1992 and 2014 (retrospectively) and 2015 and 2019 (prospectively). Their histomorphologic diagnoses were classified as two categories: (1) acute-angled branching, septate hyphae with parallel walls and a uniform width ('morphologic aspergillosis') and (2) right-angled branching pauciseptate, broader and ribbon-like hyphae with nonparallel walls ('morphologic mucormycosis').Results: A total of 113 patients were finally analysed and their histomorphologic diagnoses were classified as follows: 51 (45%) with morphologic aspergillosis, 62 (55%) with morphologic mucormycosis. Of the 51 patients with morphologic aspergillosis, 46 (90%) received the same diagnosis based on culture and/or IHC, and the remaining five (10%) gave positive IHC result for mucormycosis. Of the 62 patients with morphologic mucormycosis, 60 (97%) had the same diagnosis based on culture and/or IHC, and the remaining two (3%) yielded a positive aspergillus culture or a positive IHC result for aspergillosis, respectively.Conclusions: The majority of histomorphologic diagnoses appear to be consistent with definitive diagnoses based on sterile culture and IHC tests. However, about 10% of 'morphologic aspergillosis' diagnoses were mucormycosis cases.

Coronavirus disease 2019 (COVID-19) vaccination in immunocompromised, especially transplant recipients, may induce a weaker immune response. But there are limited data on the immune response after COVID-19 vaccination in liver transplant (LT) recipients, especially on the comparison of Ab responses after different vaccine platforms between mRNA and adenoviral vector vaccines. Thus, we conducted a prospective study on LT recipients who received two doses of the ChAdOx1 nCoV-19 (ChAdOx1), mRNA-1273, or BNT162b2 vaccines compared with healthy healthcare workers (HCWs). SARS-CoV-2 S1-specific IgG Ab titers were measured using ELISA. Overall, 89 LT recipients (ChAdOx1, n=16 [18%]) or mRNA vaccines (mRNA-1273 vaccine, n=23 [26%]; BNT162b2 vaccine, n=50 [56%]) received 3 different vaccines. Of them, 16 (18%) had a positive Ab response after one dose of COVID-19 vaccine and 62 (73%) after 2 doses. However, the median Ab titer after two doses of mRNA vaccines was significantly higher (44.6 IU/ml) than after two doses of ChAdOx1 (19.2 IU/ml, p=0.04). The longer time interval from transplantation was significantly associated with high Ab titers after two doses of vaccine (p=0.003). However, mycophenolic acid use was not associated with Ab titers (p=0.53). In conclusion, about 3-quarters of LT recipients had a positive Ab response after 2 doses of vaccine, and the mRNA vaccines induced higher Ab responses than the ChAdOx1 vaccine.

The challenges for the South Korean security policy are twofold: North Korean nuclear threat and United States–China strategic competition. To deal with such challenges, South Korea’s security policy has mainly been focused on the denuclearization of North Korea and the strengthening of the Republic of Korea (ROK)–US alliance. In addition, the future warfare between the United States and China would be extended to every sector of information and communication technology (ICT), including next-generation semiconductors, artificial intelligence, and quantum computing. South Korea is thus making efforts to move away from straddling between the United States and China, while avoiding the zero-sum mentality. But the three sets of competing beliefs remain another challenge for South Korea’s advanced security policy: (a) inter-Korean versus alliance schools in dealing with North Korean issues; (b) ROK–Japan deteriorating relations versus increasing need for ROK–US–Japan security cooperation; and (c) the ‘South–South Conflict’ that hampers the implementation of consistent security policy.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, subsequent ChAdOx1 nCoV-19 vaccination induced similar neutralizing antibody levels against the original strain but significantly higher levels against the Omicron variant compared to those who were not vaccinated. Prior SARS-CoV-2 infection exhibited higher neutralization antibody titers than vaccination alone for both original strains and the Omicron variant.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne disease in East Asia that is causing high mortality. The Gn glycoprotein of the SFTS virus (SFTSV) has been considered to be an essential target for virus neutralization. However, data on anti-Gn glycoprotein antibody kinetics are limited. Therefore, we investigated the kinetics of Gn-specific antibodies compared to those of nucleocapsid protein (NP)-specific antibodies. A multicenter prospective study was performed in South Korea from January 2018 to September 2021. Adult patients with SFTS were enrolled. Anti-Gn-specific IgM and IgG were measured using an enzyme-linked immunosorbent assay. A total of 111 samples from 34 patients with confirmed SFTS were analyzed. Anti-Gn-specific IgM was detected at days 5–9 and peaked at day 15–19 from symptom onset, whereas the anti-NP-specific IgM titers peaked at days 5–9. Median seroconversion times of both anti-Gn- and NP-specific IgG were 7.0 days. High anti-Gn-specific IgG titers were maintained until 35–39 months after symptom onset. Only one patient lost their anti-Gn-specific antibodies at 41 days after symptom onset. Our data suggested that the anti-Gn-specific IgM titer peaked later than anti-NP-specific IgM, and that anti-Gn-specific IgG remain for at least 3 years from symptom onset.

Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P qac genes, and molecular characterization of their plasmids, are needed to understand their role in MRSA epidemiology.

Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

To evaluate the effects of isolating coronavirus disease 2019 (COVID-19) patients in general wards, we compared the rates of COVID-19 infection in nurses and nursing assistants working in COVID-19 designated wards and in general wards of our hospital from 1 October 2021 to 21 April 2022.This study was conducted in a 2,700-bed tertiary care hospital in Seoul, Korea. Designated wards comprised single, negative pressure rooms and a 100% outdoor air system.During the study period, a total of 2,698 nurses and nursing assistants were employed at our hospital, of whom 310 (11%) were working in the designated wards, and the remaining 2,388 (89%) in the general wards, and among whom 1,158 (43%) were diagnosed with COVID-19. The healthcare workers (HCWs) in the designated wards were less frequently diagnosed with COVID-19 than those in the general wards (31% vs. 45%,HCWs in designated wards have a lower rate of contracting COVID-19 than those in general wards. A lack of exposure to undiagnosed cases and their caregivers, greater care with social distancing outside the hospital, higher rates of 3-dose vaccinations, and the use of isolation rooms with negative pressure may be associated with this finding.

We evaluated the association between antiviral treatment duration and relapse of gastrointestinal (GI) cytomegalovirus (CMV) disease by analyzing the risk factors for relapse. Patients who were diagnosed with GI CMV disease at a tertiary hospital from January 2008 to April 2019 were retrospectively enrolled. Patients with relapsed disease were those with a recurrence of GI CMV disease at least 4 weeks after the initial antiviral treatment. Of 238 participants, including 145 (51.9%) with upper and 93 (48.1%) with lower GI CMV diseases, 27 (11.3%) had experienced relapses. The difference in antiviral treatment duration between the relapsed and nonrelapsed GI CMV groups was not significant (median days, 21.0 vs 17.0, P = .13). Multivariate analysis revealed that hematologic malignancy (odds ratio, 3.73; P = .026) and ulcerative colitis (odds ratio, 4.61; P = .003) were independent risk factors for relapse. Participants with at least one of these risk factors and those with no independent risk factors were classified under the high- (relapse rate, 25.9%) and low-risk of relapse groups (relapse rate, 6.7%), respectively. Accordingly, we further stratified 180 (75.6%) and 58 (24.4%) participants under the low- and high-risk of relapse groups, respectively. There was no significant difference in relapse rates between the high- and low-risk groups according to antiviral treatment duration. Approximately 10% of the participants experienced relapses after antiviral treatment, with hematologic malignancy and ulcerative colitis featuring as risk factors. Therefore, prolonged antiviral treatment might not be helpful in preventing GI CMV disease relapse.

Background Preventive measures are needed to reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). Notably, hospital staff are usually exposed when they are unmasked. There are limited data on the risk of transmission during mealtimes at hospital staff cafeterias. We aimed to evaluate the risk of transmission in cafeterias. Methods From January 2020 through September 2021, we analyzed the risk of SARS-CoV-2 transmission through closed-circuit television and radio-frequency identification tracking and follow-up testing when 33 HCWs, who were eventually diagnosed as coronavirus disease 2019 (COVID-19), ate in staff cafeterias during the infectious period. The seats were arranged so the HCWs would sit on either side without facing each other. There were no plastic barriers installed, and HCWs were encouraged not to talk during meals. Results Three of the 119 individuals who ate at seats next (about 30 cm) to index during the period of transmission and underwent follow-up SARS-CoV-2 polymerase chain reaction tests were diagnosed with COVID-19 (2.5%; 95% confidence interval, 0.5–7.4%). Among the 98 HCWs who were investigated about talking during meals, there was a higher attack rate among those who spoke with each other than among those who did not (12.5% [3/24] vs. 0% [0/74], P = 0.013). Conclusion The risk of transmission in a hospital’s employee cafeterias is not high with side-by-side seating, especially in the absence of conversation., Graphical Abstract

Background We aimed to compare the clinical outcomes of patients with positive Xpert Carba-R assay results for carbapenemase-producing Enterobacterales (CPE) according to CPE culture positivity. Methods We retrospectively collected data for patients with positive CPE (positive Xpert Carba-R or culture) who underwent both tests from August 2018 to March 2021 in a 2700-bed tertiary referral hospital in Seoul, South Korea. We compared the clinical outcomes of patients positive for Xpert Carba-R according to whether they were positive (XPCP) or negative (XPCN) for CPE culture. Results Of 322 patients with CPE who underwent both Xpert Carba-R and culture, 313 (97%) were positive for Xpert Carba-R for CPE. Of these, 87 (28%) were XPCN, and 226 (72%) were XPCP. XPCN patients were less likely to have a history of previous antibiotic use (75.9% vs 90.3%; P = .001) and to have Klebsiella pneumoniae carbapenemase (21.8% vs 48.9%; P Conclusions Our study suggests that XPCN patients had lower rates of both infection and transmission than XPCP patients. The Xpert Carba-R assay is clinically useful not only for rapid identification of CPE but also for predicting risks of infection and transmission when performed along with culture.

The potential for a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from a fully vaccinated individual is largely unknown.In October 2021, during the time when the delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in two wards in a tertiary care hospital in Seoul, Korea. We performed airflow investigations and whole-genome sequencing (WGS) of the virus.The index patient developed symptoms 1 day after admission, and was diagnosed with COVID-19 on day 4 post-admission. He was fully vaccinated (ChAdOx1 nCoV-19) 2 months before the diagnosis. Three inpatients and a caregiver in the same room, two inpatients in an adjacent room, two inpatients in rooms remote from the index room, and one nurse on the ward tested positive. Also, two resident doctors who stayed in an on-call room located on the same ward tested positive (although they had no close contact), as well as a caregiver who stayed on an adjacent ward, and a healthcare worker who had casual contact with this caregiver. Samples from five individuals were available for WGS, and all showed ≤ 1 single-nucleotide polymorphism difference. CCTV footage showed that the index case walked frequently in the corridors of two wards. An airflow study showed that the air from the corridor flowed into the resident on-call room, driven by an air circulator that was always turned on.Transmission of severe acute respiratory syndrome coronavirus 2 from a fully vaccinated index occurred rapidly via the wards and on-call room. Care must be taken to not use equipment that can change the airflow.

Rapid, sensitive, and specific detection of the severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 during early infection is pivotal in controlling the spread and pathological progression of Coronavirus Disease 2019 (COVID-19). Thus, highly accurate, affordable, and scalable point-of-care (POC) diagnostic technologies are necessary. Herein, we developed a rapid and efficient self-directed molecular diagnostic (SdMDx) system for SARS-CoV-2. This system combines the sample preparation step, including virus enrichment and extraction processes, which involve dimethyl suberimidate dihydrochloride and diatomaceous earth functionalized with 3-aminopropyl(diethoxy)methylsilane, and the detection step using loop-mediated isothermal amplification-lateral flow assay (LAMP-LFA). Using the SdMDx system, SARS-CoV-2 could be detected within 47 min by hand without the need for any larger instruments. The SdMDx system enabled detection as low as 0.05 PFU in the culture fluid of SARS-CoV-2-infected VeroE6 cells. We validated the accuracy of the SdMDx system on 38 clinical nasopharyngeal specimens. The clinical utility of the SdMDx system for targeting the S gene of SARS-CoV-2 showed 94.4% sensitivity and 100% specificity. This system is more sensitive than antigen and antibody assays, and it minimizes the use of complicated processes and reduces contamination risks. Accordingly, we demonstrated that the SdMDx system enables a rapid, accurate, simple, efficient, and inexpensive detection of SARS-CoV-2 at home, in emergency facilities, and in low-resource sites as a pre-screening platform and POC testing through self-operation and self-diagnosis.

This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC).A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater.Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). We investigated the detailed kinetics of serologic response in patients with SFTS. Twenty-eight patients aged ≥18 years were enrolled between July 2015 and October 2018. SFTS was confirmed by detecting SFTSV RNA in their plasma using reverse transcription polymerase chain reaction. SFTSV-specific IgG and IgM were measured using immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). We found that SFTSV-specific IgG was detected at days 5–9 after symptom onset, and its titer was rising during the course of disease. SFTSV-specific IgM titer peaked at around week 2–3 from symptom onset. The SFTSV-specific seropositive rates for days 5–9, 10–14, 15–19, and 20–24 from symptom onset using IFA and ELISA were 63%, 76%, 90%, and 100%, and 58%, 86%, 100%, and 100%, respectively, for IgG, whereas they were 32%, 62%, 80%, and 100%, and 53%, 62%, 70%, and 100%, respectively, for IgM. The delayed IgM response could be attributed to the low sensitivity of SFTSV-specific IgM IFA or ELISA and/or impaired immune responses. The IgM test using IFA or ELISA that we used in this study is, therefore, insufficient for the early diagnosis of SFTS.

Background Data on the clinical and virological characteristics of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This prospective cohort study compared the characteristics of the Delta variant to other variants. Methods Adult patients with mild coronavirus disease 2019 (COVID-19) who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcription polymerase chain reaction (PCR). Cell cultures were performed on saliva samples with positive genomic RNA results. Results A total of 141 patients (Delta group, n = 108 [77%]; non-Delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the Delta group than in the non-Delta group (52% vs 27%, P = .03). Total symptom scores were significantly higher in the Delta group between days 3 and 10 after symptom onset. Initial genomic RNA titers were similar between the 2 groups; however, during the late course of disease, genomic RNA titers were higher in the Delta group. Negative conversion of subgenomic RNA was slower in the Delta group (median 9 vs 5 days; P Conclusions COVID-19 patients infected with the Delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-Delta variants.

β-lactam–avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime–avibactam and aztreonam–avibactam against extended-spectrum β-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum β-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime–avibactam, and aztreonam–avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime–avibactam and 99% had low aztreonam–avibactam MICs (≤8 mg/L). Ceftazidime–avibactam and aztreonam–avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam–avibactam was more active than ceftazidime–avibactam. The frequencies of the inoculum effect with ceftazidime–avibactam and aztreonam–avibactam were lower than with meropenem (14% vs. 38%, p < 0.001 and 30% vs. 38%, p = 0.03, respectively). The β-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam–avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime–avibactam.

Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.

Background/Aims: Data comparing the antibody responses of different coronavirus disease 2019 (COVID-19) vaccine platforms according to dose with natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced antibody responses are limited.Methods: Blood samples from adult patients with mild and severe COVID-19 and healthcare workers who received ChAdOx1 nCoV-19 vaccine (2nd dose at 12-week intervals) and BNT162b2 vaccine (2nd dose at 3-week intervals) were collected and compared by immunoglobulin G immune responses to SARS-CoV-2 specific spike protein using an in-house-developed enzyme-linked immunosorbent assay.Results: A total of 53 patients, including 12 and 41 with mild and severe COVID-19, respectively, were analyzed. In addition, a total of 73 healthcare workers, including 37 who received ChAdOx1 nCoV-19 and 36 who received BNT162b2, were enrolled. Antibody responses after the first and second doses of the ChAdOx1 nCoV-19 vaccine or the first dose of the BNT162b2 vaccine were similar to those in convalescent patients with mild COVID-19, but lower than those in convalescent patients with severe COVID-19, respectively. However, after the second dose of the BNT162b2 vaccine, the antibody response was comparable to that in convalescent patients with severe COVID-19.Conclusions: Our data suggest that the second dose of mRNA vaccination may be more beneficial in terms of long-term immunity and prevention of SARS-CoV-2 variant infection than a single dose of COVID-19 vaccination or homologous second challenge ChAdOx1 nCoV-19.

The value of follow-up blood culture (FUBC) in Gram-negative bacteremia (GNB) management is controversial. We evaluated bedside risk predictors and their probabilities of yielding positive FUBCs in GNB.All adult patients with GNB in a 2700-bed tertiary center were retrospectively enrolled between January 2019 and December 2019. Only one initial GNB episode was included per patient. Positive FUBC was defined as isolation of the same organism in blood culture 48-72 h after the initial blood culture.A total of 2216 patients with GNB were identified, of whom 34.4% underwent FUBC. Of the 645 patients with FUBCs analyzed in the study, 89 (13.8%) had positive FUBCs. In multivariate analysis, hemodialysis [adjusted odds ratio (aOR), 2.6], fever on the day of FUBCs (aOR 3.6), intravascular device (aOR 2.4), no use of in vitro active antibiotic within 24 h (aOR 2.5), non-fermenting bacteria (aOR 4.7), and multidrug resistance (aOR 5.4) were independent risk factors for positive FUBCs. If microbiological results were excluded in multivariate analysis, hemodialysis, immunosuppressive treatment, fever on the day of FUBCs, and intravascular device were independent bedside risk predictors for positive FUBCs. The yield of FUBCs increased from 3.0% (95% CI 1.0-7.0) to 63.6% (95% CI 25.6-100) as the number of bedside risk predictors increased from 0 to 4. In addition, positive FUBCs were significantly associated with 30 day mortality.FUBCs may not need to be routinely used for patients with GNB bacteremia, and bedside risk predictors could be helpful in identifying patients for whom FUBC is likely to be useful.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, is rapidly spreading and severely straining the capacities of public health communities and systems around the world. Therefore, accurate, rapid, and robust diagnostic tests for COVID-19 are crucial to prevent further spread of the infection, alleviate the burden on healthcare and diagnostic facilities, and ensure timely therapeutic intervention. To date, several detection methods based on nucleic acid amplification have been developed for the rapid and accurate detection of SARS-CoV-2. Despite the myriad of advancements in the detection methods for SARS-CoV-2, rapid sample preparation methods for RNA extraction from viruses have rarely been explored. Here, we report a rapid COVID-19 molecular diagnostic system that combines a self-powered sample preparation assay and loop-mediated isothermal amplification (LAMP) based naked-eye detection method for the rapid and sensitive detection of SARS-CoV-2. The self-powered sample preparation assay with a hydrophilic polyvinylidene fluoride filter and dimethyl pimelimidate can be operated by hand, without the use of any sophisticated instrumentation, similar to the reverse transcription (RT)-LAMP-based lateral flow assay for the naked-eye detection of SARS-CoV-2. The COVID-19 molecular diagnostic system enriches the virus population, extracts and amplifies the target RNA, and detects SARS-CoV-2 within 60 min. We validated the accuracy of the system by using 23 clinical nasopharyngeal specimens. We envision that this proposed system will enable simple, facile, efficient, and inexpensive diagnosis of COVID-19 at home and the clinic as a pre-screening platform to reduce the burden on the medical staff in this pandemic era.

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.