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Estimating neutralizing activity in vaccinees is crucial for predicting the protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the plaque reduction neutralization test (PRNT) requires a biosafety level 3 facility, it would be advantageous if surrogate virus neutralization test (sVNT) assays and binding assays could predict neutralizing activity. Here, five different assays were evaluated with respect to the PRNT in vaccinees: three sVNT assays from GenScript, Boditech Med, and SD Biosensor and two semiquantitative binding assays from Roche and Abbott. The vaccinees were subjected to three vaccination protocols: homologous ChAdOx1, homologous BNT162b2, and heterologous administration. The ability to predict a 50% neutralizing dose (ND

Background Antibiotic resistance threatens public health worldwide, and inappropriate use of antibiotics is one of the main causes. Antibiotic use for asymptomatic bacteriuria (ABU) has been defined as “antibiotics never events”, and urinary tract infection (UTI) is one of the most common infectious diseases for which antibiotics are prescribed in Korea. To establish an effective antimicrobial stewardship strategy, a qualitative assessment of antibiotic use in actual clinical syndrome is necessary. Methods Cases of positive urine cultures (≥105 CFU/ml), performed in inpatient, outpatient, and emergency departments in April 2021 were screened in 26 hospitals located throughout Korea. Cases were classified into ABU, lower UTI, and upper UTI. The appropriateness of antibiotic use was retrospectively evaluated by infectious disease specialists using quality indicators based on the domestic clinical guideline for ABU and UTI. Figure 1.Study flow diagram Results A total of 2697 cases of ABU or UTI were included. The appropriateness of antibiotic use was assessed in 1157 cases with asymptomatic bacteriuria, 677 and 863 cases with lower and upper UTI (Figure 1). Antibiotics were prescribed in 21.7% (251 of 1157) of ABU without appropriate indication. Of 66 ABU cases with appropriate indication in which prophylactic antibiotics were prescribed, the duration of antibiotics was adequate in only 34.8% (Table 1). For lower UTI, the appropriateness of empirical and definite antibiotics was 77.8% (527 of 677) and 68.0% (353 of 519). In terms of upper UTI, 86.3% (745 of 863) and 78.2% (583 of 746) was appropriate, respectively. The duration of antibiotics was adequate in 65.7% (421 of 641) of lower UTI and 77.9% (592 of 760) in upper UTI (Table 2, 3). Conclusion This nationwide qualitative assessment of antibiotic use in ABU and UTI revealed that a significant proportion of antibiotics were prescribed inappropriately and, furthermore the duration of antibiotics was prolonged unnecessarily. Interventions for appropriate antibiotic use in ABU and UTI at the national level are required. Disclosures All Authors: No reported disclosures.

We report a case of human granulocytic anaplasmosis (HGA) in a 76-year-old woman, diagnosed rapidly based on the characteristic peripheral blood smear finding of intragranulocytic morulae. The smear was prepared on the day of hospitalization, which was 1-2 weeks before results of the serology test or polymerase chain reaction (PCR) became available. Owing to the blood smear test, we could start timely and appropriate antimicrobial treatment. The sensitivity of peripheral blood smear is lower compared to that of serology or PCR for the diagnosis of HGA but may increase with the examiner's experience. In our case, the diagnosis of HGA was confirmed based on PCR and serology 7 and 14 days after the positive peripheral blood smear test, respectively. Morulae in neutrophils are a diagnostic indicator of HGA, particularly for febrile patients with a history of tick bites or outdoor activities in rural areas.

Background South Korea has been providing 10-valent pneumococcal conjugate vaccine/(PCV10)/13-valent pneumococcal conjugate vaccine (PCV13) to children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to older adults as part of a national immunization program. Methods From September 2015 to August 2017, a prospective cohort study was conducted for adults aged ≥19 years with community-acquired pneumonia (CAP) at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated on the basis of hospital catchment population. Serotype distribution of pneumococcal CAP was also evaluated. Results Among 2669 patients with CAP, 252 cases (9.4%) were pneumococcal CAP cases. The annual incidences of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases respectively, per 100,000 persons. Serotyped Streptococcus pneumoniae was identified in 107 cases (42.5%) through culture or a serotype-specific urinary antigen detection assay. Pneumococcal CAP caused by the PCV13 and PPSV23 serotypes were 50 cases (46.7% of serotyped pneumococcal CAP and 19.8% of pneumococcal CAP), and 83 cases (77.6% of serotyped pneumococcal CAP and 32.9% of pneumococcal CAP), respectively. The most prevalent serotype was 3 (n = 21, 19.6% of serotyped pneumococcal CAP), followed by 19A (n = 10, 9.3% of serotyped pneumococcal CAP) and 11A (n = 10, 9.3% of serotyped pneumococcal CAP). Compared with non-pneumococcal CAP patients, pneumococcal CAP patients were more likely to have a higher CURB-65 scores (P = 0.002). The overall 30-day mortality rate of pneumococcal CAP was higher than that of non-pneumococcal CAP (6.3% versus 5.6%; odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67–1.96), but this trend was reversed in patients aged 65–74 years (4.2% versus 8.6%; OR, 0.47; 95% CI, 0.14–1.54). Conclusions The disease burden of PCV13-serotype pneumococcal CAP remains significantly high in Korean adults, particularly among elderly people, even after a high uptake of pediatric PCVs.

Background Hemorrhagic fever with renal syndrome is a serious health problem in Eurasian countries. This study aimed to evaluate the immunogenicity and safety of formalin-inactivated Hantaan virus vaccine (Hantavax®) with a 3 + 1 vaccination schedule. Methods A phase III, multi-center clinical trial was conducted to evaluate the immunogenicity and safety of Hantavax® (three primary doses and a booster dose schedule at 0, 1, 2 and 13 months) among healthy adults. Immune responses were assessed using the plaque reduction neutralizing antibody test (PRNT) and immunofluorescent antibody assay (IFA). Systemic and local adverse events were assessed. Results A total of 320 healthy subjects aged ≥19 years were enrolled. Following three primary doses of Hantavax®, the seroconversion rate was 80.97% and 92.81% by PRNT and IFA, respectively. With booster administration, seropositive rates were 67.47% and 95.68% at one-month post-vaccination according to PRNT and IFA, respectively. Solicited local and systemic adverse events were reported in 30.50–42.81% and 16.67–33.75% during the three primary dose vaccination, while those were reported 36.57% and 21.36% after the booster doses. Both local and systemic adverse events did not increase with repeated vaccinations. Conclusion Hantavax® showed a high seroconversion rate after the three-dose priming, and additional dose administration with 11-month interval induced good booster effects. (ClinicalTrials.gov Identifier: NCT02553837).

Background After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist. Objectives We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes. Methods Data were retrospectively collected from the hospital‐based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited. Results A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P

Background The number of human Q fever cases in South Korea has been rapidly increasing since 2015. We report the first isolation of Coxiella burnetii in Korea in two patients who initially presented with non-specific febrile illness and were finally diagnosed with acute Q fever in South Korea. Case presentation Two adult patients with fever had serologic tests against C. burnetii initially negative, and polymerase chain reaction against 16S rRNA using whole blood was also negative. After bacterial amplification of C. burnetii in immune-depressed mice, we isolated C. burnetii from patients with acute Q fever. The isolates KZQ2 and KZQ3 were confirmed by polymerase chain reaction, nucleotide sequence analysis, and morphologic observation using a transmission electron microscope. Conclusions These results can help us understand the clinical and epidemiologic features of Q fever in South Korea.

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.

The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.

Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

Background Annually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results. Methods During the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention. Results During the first A/H3N2-dominant season in 2012–2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15–77). In the latter two seasons (2013–2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only. Conclusion During consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate.

Background While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population. Methods For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100. Results We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) −5.8%–51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65–74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4–77.5)] and against NBPP [effectiveness 35.0% (2.3–56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6–98.8) for PPV23-unique serotypes and 81.3% (38.6–94.3) for PPV23 serotypes excluding serotype 3. Conclusions This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.

We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups.We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey.We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p 0.001). The neutralizing antibody titer of the heterologous group (geometric mean NDHeterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than non-response considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions. Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

Background Despite use of the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) over the last decade, the disease burden of pneumococcal pneumonia is still high. We evaluated the field effectiveness of PCV13, PPSV23, and sequential vaccination against pneumococcal pneumonia in older adults. Methods This prospective multicenter study was conducted in adults aged ≥65 years hospitalized with community-acquired pneumonia (CAP) between September 2015 and August 2017. The case-control test-negative design was used to estimate vaccine effectiveness (VE) against pneumococcal CAP. Results Of 1525 cases with CAP hospitalization, 167 (11.0%) were identified as pneumococcal CAP. In the elderly aged ≥65 years, the adjusted VE of pneumococcal vaccines against pneumococcal CAP was statistically insignificant: 40.0% (95% confidence interval [CI], –10.8% to 67.5%) for PCV13 and 11.0% (95% CI, –26.4% to 37.3%) for PPSV23. However, in the younger subgroup (aged 65–74 years), sequential PCV13/PPSV23 vaccination showed the highest adjusted VE of 80.3% (95% CI, 15.9%–95.4%), followed by single-dose PCV13 (adjusted VE, 66.4% [95% CI, .8%–88.6%]) and PPSV23 (adjusted VE, 18.5% [95% CI, –38.6% to 52.0%]). Conclusions Sequential PCV13/PPSV23 vaccination is most effective for preventing pneumococcal CAP among the elderly aged 65–74 years.

Background In South Korea, the number of Q fever cases has rapidly increased since 2015. Therefore, this study aimed to characterize the epidemiological and clinical features of Q fever in South Korea between 2011 and 2017. Methods/Principal findings We analyzed the epidemiological investigations and reviewed the medical records from all hospitals that had reported at least one case of Q fever from 2011 to 2017. We also conducted an online survey to investigate physicians’ awareness regarding how to appropriately diagnose and manage Q fever. The nationwide incidence rate of Q fever was annually 0.07 cases per 100,000 persons. However, there has been a sharp increase in its incidence, reaching up to 0.19 cases per 100,000 persons in 2017. Q fever sporadically occurred across the country, with the highest incidences in Chungbuk (0.53 cases per 100,000 persons per year) and Chungnam (0.27 cases per 100,000 persons per year) areas. Patients with acute Q fever primarily presented with mild illnesses such as hepatitis (64.5%) and isolated febrile illness (24.0%), whereas those with chronic Q fever were likely to undergo surgery (41.2%) and had a high mortality rate (23.5%). Follow-up for 6 months after acute Q fever was performed by 24.0% of the physician respondents, and only 22.3% of them reported that clinical and serological evaluations were required after acute Q fever diagnosis. Conclusions Q fever is becoming an endemic disease in the midwestern area of South Korea. Given the clinical severity and mortality of chronic Q fever, physicians should be made aware of appropriate diagnosis and management strategies for Q fever., Author summary Human Q fever, zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations, from self-limited febrile illnesses to endocarditis. It is usually diagnosed using serological tests. Because of the diagnostic challenge and nonspecific symptoms, it has been considered an underrecognized infectious disease, particularly in non-endemic or non-epidemic areas. In South Korea, Q fever was designated as a notifiable disease in 2006, and the number of Q fever cases has increased sharply since 2015. This study shows that Q fever is becoming an endemic disease in the midwestern area of South Korea. In this study, patients with acute Q fever primarily presented with mild illnesses such as hepatitis (64.5%) and isolated febrile illness (24.0%). However, patients with chronic Q fever presented with vascular infection (52.9%) and endocarditis (35.3%); such patients were likely to undergo surgery (41.2%) and had a high mortality rate (23.5%). We also surveyed physicians’ awareness regarding how to appropriately diagnose and manage Q fever. This survey showed that more than half of the physicians did not follow-up suspected patients with acute Q fever who had negative serological results at the early stage of illness using a serological test and that follow-ups for identifying chronic Q fever after primary C. burnetii infection were only performed by 24.0% of physicians.

Cases of laboratory-confirmed SARS-CoV-2 reinfection have been reported in a number of countries. Further, the level of natural immunity induced by SARS-CoV-2 infection is not fully clear, nor is it clear if a primary infection is protective against reinfection. To investigate the potential association between serum antibody titres and reinfection of SARS-CoV-2, ferrets with different levels of NAb titres after primary SARS-CoV-2 infection were subjected to reinfection with a heterologous SARS-CoV-2 strain. All heterologous SARS-CoV-2 reinfected ferrets showed active virus replication in the upper respiratory and gastro-intestinal tracts. However, the high NAb titre group showed attenuated viral replication and rapid viral clearance. In addition, direct-contact transmission was observed only from reinfected ferrets with low NAb titres (

Objectives The aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus. Methods To demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection. Results SARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16–2.09 ± 0.85 log10 copies/mL, saliva 1.07 ± 0.34–1.65 ± 0.46 log10 copies/mL, stool 1.17 ± 0.32 log10 copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12–1.34 ± 0.30 log10 copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool. Discussion Viable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11–15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. Methods A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. Results Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score 5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). Conclusions After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score, Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. In patients with SFTS, steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score

Highlights • To counteract COVID-19 pandemics, more airborne-infection isolation rooms are needed • Negative air machines can generate negative pressure in patient rooms. • Every effort should be made to equip anterooms in airborne-infection isolation rooms. • When selecting isolation rooms, oxygen and medical air supply should be checked., More airborne-infection isolation rooms are needed in centers that treat severely affected coronavirus 2019 patients. Wards and rooms must be carefully checked to ensure an ample supply of medical air and oxygen. Anterooms adjacent to airborne-infection isolation rooms are required to maintain pressure differentials and provide an area for donning/doffing or disinfecting medical equipment.

Background Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Asian 3 countries, China, Japan and Korea, which are scrub typhus endemic areas, and its incidence is increasing. As the two infections overlap epidemiologically and clinically and the accessibility or sensitivity of diagnostic tests is limited, early clinical prediction may be useful for diagnostic and therapeutic purposes. Methods Patients aged ≥16 years who were clinically suspected and laboratory-confirmed to be infected with Orientia tsutsugamushi or the SFTS virus in South Korea were enrolled. Clinical and laboratory parameters were compared. Scrub typhus was further subclassified according to the status of eschar and skin rash. An SFTS prediction scoring tool was generated based on a logistic regression analysis of SFTS compared with scrub typhus. Results The analysis was performed on 255 patients with scrub typhus and 107 patients with SFTS. At initial presentation, subjective symptoms except for gastrointestinal symptoms, were more prominent in scrub typhus patients. In addition to the characteristic eschar and skin rash, headache was significantly more prominent in scrub typhus, while laboratory abnormalities were more prominent in SFTS. Leukopenia (white blood cell count

Objectives: This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK). Methods: Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015. Results: A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18–49 years, 23.7% in those aged 50–64 years, 33.0% in those aged 65–74 years, and 51.0% in those aged ≥75 years (p

We aimed to characterize the lineages of influenza B viruses obtained from clinical specimens during the 2007-2014 seasons in South Korea. RT-PCR for the partial hemagglutinin gene of influenza B virus was performed on laboratory-confirmed influenza B samples from the 2007-2008 season to 2013-2014 season. A phylogenetic tree was generated, and current influenza vaccine strains for the Northern Hemisphere were used as representative strains of Victoria and Yamagata lineages. A total of 571 influenza B virus sequences were analyzed. During the 2009-2010 season, most of the circulating influenza B viruses matched the vaccine strain; 91.0% (91/100) of viruses belonged to the Victoria lineage. In the 2007-2008, 2011-2012, and 2013-2014 seasons, co-circulation of each influenza B lineage was found with a match ratio to the vaccine strain of 53.2% (42/79), 40.9% (63/154), and 58.3% (134/230), respectively. Overall, 41.7% (238/571) of the circulating influenza B viruses belonged to the lineage mismatching the vaccine strain. During the seven influenza seasons, influenza B epidemics were substantial in four seasons in South Korea. Significant mismatches of the vaccine and lineage of the circulating influenza B viruses were found. The current trivalent influenza vaccine may not be fully suitable for effective protection against influenza B.

During January 2013-April 2014, we subjected nasopharyngeal specimens collected from patients with acute febrile respiratory illness in a military hospital to PCR testing to detect 12 respiratory viruses and sequence a partial hexon gene for human adenovirus (HAdV) molecular typing. We analyzed the epidemiologic characteristics of HAdV infections and compared clinical characteristics of HAdV types. Among the 305 patients with acute febrile respiratory illness, we detected respiratory viruses in 139 (45.6%) patients; HAdV was the most prevalent virus (69 cases). Of the 40 adenoviruses identified based on type, HAdV-55 (29 cases) was the most prevalent, followed by HAdV-4 (9 cases). HAdV-55 was common in patients with pneumonia (odds ratio 2.17; 95% CI 0.48-9.86) and hospitalized patients (odds ratio 5.21; 95% CI 1.06-25.50). In soldiers with HAdV infection in Korea, HAdV-55 was the most prevalent type and might be associated with severe clinical outcomes.

Background The influenza virus is reportedly associated with 3-5 million cases of severe illness and 250 000-500 000 deaths annually worldwide. Objectives We investigated the variation of influenza A virus in Korea and examined the association with death. Methods A total of 13 620 cases were enrolled in the Hospital-based Influenza Morbidity & Mortality surveillance system in Korea during 2011-2016. Among these cases, a total of 4725 were diagnosed with influenza using RT-PCR (influenza A; n = 3696, influenza B; n = 928, co-infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs. Results We found that the sequences of A/H3N2 in the 2011-2012 season belong to subgroup 3C.1, whereas the sequences in the 2012-2013 season pertain to subgroup 3C.2. The sequences in the 2013-2014 and 2014-2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease. Conclusions In conclusion, influenza A virus clade changes occurred in Korea during the 2011-2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions.

Background Acute Q fever usually presents as a nonspecific febrile illness, and its occurrence is rapidly increasing in South Korea. This study investigated the clinical characteristics of acute Q fever patients in South Korea and the time from symptom onset to serologic diagnosis. The clinical courses were examined according to antibiotic treatment. Methods Data of patients diagnosed with acute Q fever at Chungbuk National University Hospital between January 2015 and February 2018 were retrospectively collected. Demographic and epidemiologic data were reviewed. The time from symptom onset to serologic diagnosis by an immunofluorescence assay (IFA) was analyzed. Clinical courses and the percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) were compared between patients administered antibiotics with anti-Coxiella burnetii activity and patients not administered such antibiotics. Results Forty-eight patients (median age: 51.5 years) were included. Most were male (95.8%) and had no history of animal contact (91.7%). The median time from illness onset to serologic diagnosis was 21 days. Thirty-nine patients received antibiotics with anti-C. burnetii activity. The length of hospital stay and fever duration did not significantly differ between patients who received antibiotics with anti-C. burnetii activity (7 and 15 days) and those who did not (5 and 8 days) (P = 0.110 and P = 0.137, respectively). The percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) did not significantly differ between patients who received antibiotics with anti-C. burnetii activity and those who did not (P = 0.340). Conclusions Most acute Q fever patients had a nonspecific febrile illness with mild elevation of transaminases and no history of animal contact or occupational risk. The time from symptom onset to a positive IFA test was longer than the fever duration in most acute Q fever patients. Consequently, it may be difficult for clinicians to serologically diagnose acute Q fever. However, inappropriate antibiotic treatment was not associated with prolongation of symptoms or progression to chronic Q fever.

Background Although human-to-human transmission of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) via direct contact with body fluids has been reported, the role of specific body fluids from SFTSV-infected hosts has not been investigated in detail. Methods To demonstrate the virus transmission kinetics in SFTSV-infected hosts, we adapted the ferret infection model and evaluated the virus shedding periods, virus titers, and transmission modes from various specimens of infected ferrets. Results Large amounts of infectious SFTSV are shed through nasal discharge, saliva, and urine from SFTSV-infected ferrets. Virus could be detected from 2 dpi and persisted until 12 dpi in these specimens, compared with the relatively short virus-shedding period in sera. Further, transmission studies revealed that SFTSV can be transmitted to close direct and indirect contact naïve animals through various mediums, especially through contact with serum and urine. Further, ferrets contacted with human urine specimens from SFTSV-positive patients were successfully infected with SFTSV, suggesting that urine specimens could be a source of SFTSV infection in humans. Conclusions Our results demonstrate that the SFTSV can be shed in various body fluids for more than 12 days and that these specimens could be a source for direct or indirect transmission through close personal contact.

Background A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. Materials and Methods Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. Results In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. Conclusion Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.

Pneumocystis jirovecii pneumonia (PJP) in patients with HIV infection can, in rare cases, present with pulmonary nodules that histologically involve granulomatous inflammation. This report describes an intriguing case of granulomatous PJP with pulmonary nodules after commencing antiretroviral therapy (ART) in an HIV-infected patient without respiratory signs or symptoms. Diagnosis of granulomatous PJP was only achieved through thoracoscopic lung biopsy. This case suggests that granulomatous PJP should be considered in the differential diagnosis of pulmonary nodules in HIV-infected patients for unmasking immune reconstitution inflammatory syndrome manifestation after initiation of ART.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-I³ (IFN-I³)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-I³-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

BackgroundInfluenza and pneumonia are leading causes of morbidity and mortality among the elderly. Although vaccination is a main strategy to prevent these infectious diseases, concerns remain with respect to vaccine effectiveness.MethodsDuring three influenza seasons (2014-2015, 2015-2016 and 2016-2017), we evaluated the effectiveness of the influenza and pneumococcal vaccines against pneumonia and acute exacerbation of cardiopulmonary diseases among the elderly aged ≥65 years with influenza-like illness (ILI). Demographic and clinical data were collected prospectively.ResultsAmong 2,119 enrolled cases, 1,302 (61.4%) and 871 (41.1%) received the influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPV23), respectively. During an A/H3N2-dominant season with poor influenza vaccine effectiveness (2014-2015 season), neither the influenza vaccine nor PPV23 showed significant effectiveness against pneumonia or acute exacerbation of cardiopulmonary diseases. During seasons with good influenza vaccine effectiveness (2015-2016 and 2016-2017 seasons), the influenza vaccine was effective in preventing pneumonia, but PPV23 was not. In particular, the influenza vaccine was effective in preventing acute exacerbation of heart diseases (75.0%) during the A/H1N1-dominant 2015-2016 season.ConclusionThe influenza vaccine was effective in preventing pneumonia only during vaccine-matched seasons with good effectiveness against circulating influenza viruses. In addition, the influenza vaccine was cardio-protective during a vaccine-matched A/H1N1-dominant season.

Background SFTS and scrub typhus have similar clinical features and difficult to differentiate. Thus, a study to develop a scoring system to differentiate between two diseases in a clinical setting before the confirmation of laboratory results was reported by Kim et al. However, the statistical power could be low because of low numbers of cases (21 SFTS, 91 scrub typhus), our study analyzed by increasing the number of cases to overcome these limitations. Methods We retrospectively collected data from 183 SFTS and 178 scrub typhus patients who visited the 21 hospitals in South Korea between October, 2013 and November, 2017. The study protocol was approved by the IRB of each institution. SFTS was diagnosed through detection of SFTS viral RNA using RT–PCR. Scrub typhus was diagnosed either detection of 56-kDa antigen of O. tsutsugamushi using nested PCR or ≥ 4 fold rise in IgM or IgG titer using indirect IFA. Statistical analyses were performed by using SPSS and Medcalc. Results To differentiate SFTS from scrub typhus, we applied the scoring system proposed by Kim et al. After multivariable logistic regression, altered mental status, leukopenia, prolonged aPTT, and normal CRP(≤ 1.0 mg/dL) were significantly associated with SFTS compared with scrub typhus. Each variable was scored by 1 point, with a total score of 0–4 points, the optimal cutoff value was > 1 for the ROC curve. A score > 1 had 92% sensitivity, 96% specificity for diagnosis of SFTS, with a ROC AUC of 0.974. Because the sensitivity was less than 95%, we changed the normal CRP criteria to ≤ 3.0 mg/dL. The modified scoring system had 97% sensitivity, 96% specificity for diagnosis of SFTS, with an AUC of 0.983, and it showed a statistically higher accuracy than original scoring system (P = 0.0487). In this study, four factors for predicting SFTS were newly developed: leukopenia, prolonged aPTT, normal CRP (≤3.0 mg/dL), and elevated CK (>1,000 IU/L). Our study scoring system had 97% sensitivity, 98% specificity for diagnosis of SFTS, with an AUC of 0.992, and it showed a statistically higher accuracy than original scoring system (P = 0.0308). Conclusion In conclusion, we can easily differentiate SFTS from scrub typhus by using our scoring system of leukopenia, prolonged aPTT, normal CRP, and elevated CK in the endemic area. Disclosures All authors: No reported disclosures.

Viable Middle East Respiratory Syndrome coronavirus (MERS-CoV) could be isolated from the environment surfaces and respiratory specimens from clinically recovered patients. Our results suggested that MERS-CoV can be transmitted through contaminated fomites, hence strict environmental hygiene, and sufficient isolation period are essential for MERS-CoV control., Background. Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. Methods. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients’ respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Conclusions. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms.

Background Previous reports mostly from Europe suggested an association between an occurrence of narcolepsy and an influenza A(H1N1)pdm09 vaccine adjuvanted with AS03 (Pandemrix ® ). During the 2009 H1N1 pandemic vaccination campaign, the Korean military performed a vaccination campaign with one type of influenza vaccine containing MF59-adjuvants. This study was conducted to investigate the background incidence rate of narcolepsy in South Korean soldiers and the association of the MF59-adjuvanted vaccine with the occurrence of narcolepsy in a young adult group. Methods To assess the incidence of narcolepsy, we retrospectively reviewed medical records of suspicious cases of narcolepsy in 2007–2013 in the whole 20 military hospitals of the Korean military. The screened cases were classified according to the Brighton Collaboration case definition of narcolepsy. After obtaining the number of confirmed cases of narcolepsy per 3 months in 2007–2013, we compared the crude incidence rate of narcolepsy before and after the vaccination campaign. Results We included 218 narcolepsy suspicious cases in the initial review, which were screened by the diagnostic code on the computerized disease registry in 2007–2013. Forty-one cases were finally diagnosed with narcolepsy in 2007–2013 (male sex, 95%; median age, 21 years). The average background incidence rate of narcolepsy in Korean soldiers was 0.91 cases per 100,000 persons per year. During the 9 months before vaccination implementation (April to December 2009), 6 narcolepsy cases occurred, whereas during the next 9 months (January to September 2010) including the 3-month vaccination campaign, 5 cases occurred. Conclusions The incidence of narcolepsy in South Korean soldiers was not increased after the pandemic vaccination campaign using the MF59-adjuvanted vaccine. Our results suggest that the MF59-adjuvanted H1N1 vaccine did not contribute to the occurrence of narcolepsy in this young adult group.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. Methodology/Principal findings In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. Conclusions/Significance Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV). During entomological surveillance of SFTSV infection in Korean ticks collected from SFTS outbreak areas, we isolated a single SFTSV strain which we designated KAGWT. In addition, we isolated three SFTSVs from human patients with typical SFTS symptoms. In this study, we report the genomic sequences of each of these isolates and compare the genetic and evolutionary characteristics between tick- and human-derived Korean SFTSV isolates. Genetic and phylogenetic analyses of these sequences revealed that the tick-derived Korean SFTSV strain is clustered into genotype B, the most prevalent genotype in South Korea, and was closely related to other SFTSV in the same group. Furthermore, our results show that at least four different genotypes of SFTSV strains are co-circulating in South Korea.

Influenza is an acute respiratory illness, which can be accompanied by complications such as pneumonia. This study was conducted to survey the clinical courses and outcomes of hospitalized adult patients with laboratory-confirmed seasonal influenza. A prospective case–control study was performed in adult influenza patients who were admitted to hospitals participating in the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system in Korea from October 2011 to May 2012. Cases with complicated influenza were compared to those without complications. A total of 123 (5.6%) patients among 2184 laboratory-confirmed adult influenza patients were hospitalized during the 2011–2012 influenza epidemic season. Forty (32.5%) experienced 50 complication episodes. Age older than 60 years (P < 0.01), male sex (P = 0.04), diabetes (P < 0.01), chronic cardiovascular disease (P < 0.01) and neuromuscular disease (P = 0.02) were significantly related to development of complications in univariate analysis. Multivariate logistic regression analysis revealed that diabetes (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.15–11.51, P = 0.02) was an independent risk factor for complicated seasonal influenza. C-reactive protein (CRP) was discriminative between complicated and uncomplicated influenza (cutoff value 13 mg/L, sensitivity 70%, specificity 74%). Complicated patients received antibiotics more frequently (P < 0.01) with longer hospital stays (P = 0.01). In conclusion, diabetic patients are at great risk for complicated influenza, and CRP would be useful to predicting complication. Therefore, early interventions such as antiviral therapy should be considered for high risk patients with diabetes, especially those with increased serum CRP level.

The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011-2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.

Influenza epidemics occur annually with variations in size and severity. Hospital-based Influenza Morbidity & Mortality was established to monitor influenza epidemics and their severity, which is composed of two surveillance systems: emergency room-based and inpatient-based surveillance. Regarding emergency room-based surveillance, influenza-like illness index (influenza-like illness cases per 1,000 emergency room-visiting subjects), number of laboratory-confirmed cases and the distribution of influenza types were estimated weekly. Inpatient-based surveillance included monitoring for hospitalization, complications, and mortality. The emergency room influenza-like illness index correlated well with the number of laboratory-confirmed influenza cases, and showed a bimodal peak at Week 4 (179.2/1,000 emergency room visits) and Weeks 13-14 (169.6/1,000 emergency room visits) of 2012. Influenza A was the predominant strain during the first epidemic peak, while influenza B was isolated exclusively during the second peak. In 2011-2012 season, the mean admission rate of emergency room-visiting patients with influenza-like illness was 16.3% without any increase over the epidemic period. Among the hospitalized patients with influenza, 33.6% (41 out of 122 patients) were accompanied by complications, and pneumonia (28.7%, 35 out of 122 patients) was the most common. Most fatal cases were caused by influenza A (96.2%) after the first epidemic peak. In conclusion, Hospital-based Influenza Morbidity & Mortality was effective for monitoring the trends in circulating influenza activity concurrently with its severity. In the 2011-2012 season, the influenza epidemic persisted for a ≥ 5-month period, with a bimodal peak of influenza A and B in sequence. Overall, influenza A was more severe than influenza B.

In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C. 2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

Background This study was performed to investigate the disease burden of seasonal influenza in adults ≥20 years of age in Korea, based on surveillance data from the Hospital-based Influenza Morbidity & Mortality Surveillance (HIMM) network. Materials and methods The HIMM network is composed of two surveillance systems: emergency room-based and inpatients-based surveillance. A total of ten university hospitals all over the country are included in the surveillance network. The adult catchment population of the HIMM network was calculated by using the data of each hospital and the database of the Health Insurance Review and Assessment Service (HIRA) of Korea. The incidence rates of laboratory-confirmed medically-attended influenza, laboratory-confirmed influenza-related admission and laboratory-confirmed influenza-related death were calculated based on the catchment population. The socioeconomic burden of influenza was estimated using the human capital approach. Results During the 2013–2014 influenza season, the calculated adult catchment population of the HIMM network was 1,380,000. The incidence of medically-attended laboratory-confirmed influenza infection was 242.8 per 100,000 adults. The incidence of laboratory-confirmed influenza-related admission was 57.9 per 100,000 adults. The incidence of laboratory-confirmed influenza-related death was 3.1 per 100,000 adults. The total socioeconomic cost of 2013–2014 seasonal influenza in Korean adult population was estimated as 125 million USD (1 USD = 1,100 KRW). Conclusion The disease burden of 2013–2014 seasonal influenza in Korean adult population is very high and indicates that more active prevention and control policies will be needed to decrease the burden. Additional researches will be needed to assess the burden of seasonal influenza in the Korean child population.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. Methods/Principal Findings SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. Conclusions SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS., Author Summary Severe fever with thrombocytopenia (SFTS) is an emerging infectious disease that was first discovered in China in 2009. Subsequently, SFTS has also been found in South Korea and Japan. Here, we report the epidemiologic and clinical characteristics of 172 confirmed SFTS cases in South Korea that occurred since the first case was reported in 2013. SFTS was prevalent throughout South Korea, except for in urban areas. The incidence was relatively low in the western and southwestern rice field areas and the scarcely populated eastern mountainous area. Hilly areas were the major endemic regions. The incidence was increasing annually, and the case fatality ratio was 32.6%. A mental status of confusion, elevated levels of C-reactive protein, and prolongation of activated partial thromboplastin time were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were noted.

Background Pneumococcal meningitis (PM) is one of invasive pneumococcal disease (IPD) and is considered as a medical emergency with notable morbidity and mortality. This study was designed to characterize differences in clinical characteristics and outcomes, pneumococcal serotypes, and antimicrobial susceptibilities between PM and pneumococcal bacteremic pneumonia (PBP) in adult patients in the Republic of Korea (ROK) from a prospective observational cohort. Methods Adult IPD cases (≥18 years) were prospectively collected from 20 hospitals participated in the pneumococcal surveillance program in the ROK from 2013 through 2015. Serotyping and antimicrobial susceptibility testing were performed by a multiplexed serotyping assay and Microscan system, respectively. Results During the study period, 30 cases of PM and 205 cases of PBP were compared. Serotypes 19A, 15B/15C, and 35B were the most prevalent among PM cases, whereas serotypes 3, 11A/D/F, and 19A were the most common serotypes in PBP. There were significant female predominance (46.7% vs. 2.3%, P = 0.022), younger age (56.7% vs. 36.1%, P = 0.031), less immunocompromised states (3.3% vs. 28.8%, P = 0.005), less underlying chronic lung diseases (3.3% vs. 16.6%, P = 0.04), and lower mortality rate (16.7% vs. 44.4%, P = 0.004) in PM, compared with PBP. However, PM cases showed higher penicillin resistance (76.7% vs. 19.2%, P < 0.001), and ceftriaxone resistance (53.3% vs. 13.4%, P < 0.001), consistent with higher MDR prevalence in PM cases (76.7% vs. 53.2 P = 0.016). All PM cases except for three cases received empiric or definite vancomycin treatment. Multiple logistic regression analysis showed that penicillin resistance (odds ratio [OR] 15.75, 95% confidence interval (CI) 3.82–64.72, P < 0.001) and survival (OR 20.73, 95% CI 3.1–136.74, P = 0.002) were significantly associated with PM. Conclusion This study indicates that adult PM showed favorable clinical outcomes, compared with PBP, despite of differences in clinical characteristics. Disclosures All authors: No reported disclosures.

Objectives: To determine the in vitro activities and interactions of imipenem, colistin and tigecycline with old antibacterial agents against carbapenem-resistant Acinetobacter baumannii. Methods: Forty-three carbapenem-resistant A. baumannli Isolates from the intensive care unit of a university hospital were collected and their MICs of imipenem, colistin and tigecycline were determined. With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill study was performed for the evaluation of antibacterial activity of colistin, tigecycline, imipenem/sulbactam and colistin/ rifampicin. Results: The time-kill study of colistin demonstrated bactericidal activity against A. baumannii at concentrations of 4x MIC and 8x MIC, whereas tigecycline showed bacteriostatic activity at all concentrations. The combination regimens of imipenem/sulbactam and colistin/rifampicin were synergistic and bactericidal at 1 x MIC. Conclusions: Imipenem/sulbactam combination, colistin and tigecycline showed good In vitro activities against carbapenem-resistant A. baumannii isolates. Even though colistin is bactericidal against carbapenem-resistant A. baumannil, the colistin/rifampicin combination is more warranted in order to be certain.

Objective.To identify the factors that inhibit or motivate influenza vaccination among healthcare workers (HCWs).Methods.In March 2000, we prepared 34-item questionnaire for both vaccine recipients and nonrecipients regarding demographic characteristics, factors motivating and inhibiting vaccination, and knowledge and attitudes about influenza vaccination. On the basis of the results of our survey, an aggressive hospital vaccination campaign was undertaken. In April 2004, after the 4-year campaign, the same questionnaire was again administered to HCWs.Results.In both 2000 and 2004, the main motives for undergoing influenza vaccination were “hospital campaign” and “recommendation by colleagues”; the percentage of respondents who were motivated by the hospital campaign had remarkably increased from 27% in 2000 to 52% in 2004 (PConclusion.We conclude that a hospital campaign can markedly improve influenza vaccination rates among HCWs. Both a mobile cart system and free vaccine supply contributed to improving the vaccination rates in our study. In addition, a specifically tailored intervention strategy was required.