Antibody Responses One Year after Mild SARS-CoV-2 Infection

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.

Antibody Responses One Year after Mild SARS-CoV-2 Infection

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.

Seroprevalence and Risk Factors for Severe Fever with Thrombocytopenia Syndrome among the Korea National Park Service Workers / 農村醫學 地域保健

Objectives@#This study was carried out to understand the seroprevalence and risk factors for severe fever with thrombocytopenia syndrome (SFTS) among the Korea National Park Service (KNPS) workers. @*Methods@#We used the stored serum samples (763) and survey results collected from the previous investigation on scrub typhus and Lyme disease among the KNPS workers during 2016-2017. The serum samples were analyzed by double-antigen sandwich enzyme-linked immunosorbent assay, which was used to test the total antibody including IgG and IgM. @*Results@#The SFTS seroprevalence among the KNPS worrkers was 1.4%. In multivariate logistic analysis, the national park exploration programs (odds ratio, 3.48; 95% confidence interval, 1.01-12.01) was significantly associated with the seroprevalence of SFTS. @*Conclusion@#This study was the first serological study of SFTS among forestry workers in South Korea. Although the KNPS workers are at a high-risk group of SFTS, the prevention activities related to the working environment and habit was insufficient. Thus, systematic prevention education and training for the KNPS workers need to be strengthened.

Prevalence and Risk Factors of Carbapenem-resistant Enterobacteriaceae Acquisition in an Emergency Intensive Care Unit in a Tertiary Hospital in Korea: a Case-Control Study

BACKGROUND: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are associated with high mortality rates and their treatment is difficult because treatment is limited to certain antibiotics, such as colistin and tigecycline. We aimed to perform active surveillance culture of CRE (ASC-CRE) to monitor the prevalence of CRE acquisition during intensive care unit (ICU) care and to examine the potential risk factors associated with CRE acquisition. METHODS: We conducted ASC-CRE on patients who were admitted to the ICU in the emergency room at a tertiary hospital. Rectal swabs were analyzed using methods established by the Centers for Disease Control and Prevention. To detect carbapenemase-producing CRE, a polymerase chain reaction assay to detect five carbapenemase genes (bla(NDM), bla(KPC), bla(VIM), bla(IMP-1), and bla(OXA-48)) was performed. RESULTS: There were 22 CRE acquisition in 21 patients (2.6%, 21/810) and the incidence of CRE acquisition was 4.3/1,000 person-days, respectively. The most common species detected was Klebsiella pneumoniae (72.7%, 16/22), and 9 carbapenemase-producing CREs (7 bla KPC and 2 bla NDM) were detected. Independent risk factors associated with CRE acquisition were men gender (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 1.3–21.3), history of admission within one year (aOR, 3.9; 95% CI, 1.2–12.1), co-colonization with multidrug-resistant Acinetobacter baumannii (aOR, 15.6; 95% CI, 3.6–67.8) and extended-spectrum β-lactamases-producing bacteria (aOR, 4.7; 95% CI, 1.5–14.6), and exposure to glycopeptide antibiotics (aOR, 3.6; 95% CI, 1.3–9.9). CONCLUSION: The identification of patients with risk factors for CRE acquisition and early detection of CRE acquisition using ASC-CRE may be useful for CRE control.

Investigation of a Mumps Outbreak in a Dental Clinic at a University Hospital / 감염과화학요법

BACKGROUND@#The Korean Society of Infectious Diseases recommends non-mandatory vaccination of newly employed healthcare workers (HCWs) with 2 measles–mumps–rubella (MMR) vaccine doses. Here, we aimed to investigate the seroprevalence of mumps among HCWs exposed to index patients with mumps and the efficacy of MMR vaccination as postexposure prophylaxis (PEP) when a mumps outbreak was encountered among HCWs in a tertiary university hospital in Korea.@*MATERIALS AND METHODS@#Four HCWs were diagnosed with mumps over a 4-day period in January 2016. Three were working at a dental clinic and one visited the clinic on the day of symptoms onset of the first patient. We investigated all HCWs who either worked in that dental clinic, visited the clinic, or being within 1.5 meter of the patients with mumps without wearing surgical masks. Seventy HCWs were exposed to 4 HCWs with mumps. We interviewed all the exposed HCWs to investigate mumps infection and MMR vaccination history; they were all tested for mumps IgG.@*RESULTS@#Of the 70 exposed HCWs, 56 (80%) were females; the median age was 34 years (range 21–59 years) and 3 had a history of mumps infection. The vaccination status verification of mumps among the HCWs was unavailable. As for serologic testing, 54 (77.1%) were seropositive. Seropositivity rate for the mumps virus in males was significantly lower than that in females (50.0% vs. 83.9% respectively, P = 0.007). A lower seroprevalence of mumps was observed among HCWs aged ≥40 years than those aged 2 days. Thirty-four (62.9%) of 54 seropositive HCWs and 16 seronegative HCWs were administered MMR vaccines as PEP and following this, no additional cases of mumps were encountered during the maximum incubation period.@*CONCLUSION@#Of the exposed HCWs, 77.1% were mumps-seropositive. Seropositive rates differed according to factors such as age and sex. Eligible HCWs received a MMR vaccine as PEP and no additional mumps cases occurred during the incubation period. It was useful in our infection control activities during the mumps outbreak.

Severe Fever with Thrombocytopenia Syndrome Patients with Hemophagocytic Lymphohistiocytosis Retrospectively Identified in Korea, 2008–2013

The incidence of severe fever with thrombocytopenia syndrome (SFTS) has increased in Korea since a first report in 2013. We investigated whether SFTS existed before 2013 using real-time reverse transcription polymerase chain reaction and stored blood samples from febrile patients with thrombocytopenia. Four cases of SFTS were identified, with the earliest occurring in 2008.

Erratum: Correction of Author Information and Funding Source: Seroprevalence of Severe Fever with Thrombocytopenia Syndrome in Southeastern Korea, 2015

The authors regret that there were errors in the article. The errors were in one co-author's affiliation and funding source.

Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients / 감염과화학요법

BACKGROUND: Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). MATERIALS AND METHODS: An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. RESULTS: A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. CONCLUSION: Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea.

A Case of Chronic Gordonia otitidis Lung Infection Initially Regarded as Nontuberculous Mycobacterial Lung Disease / 대한임상미생물학회지

The genus Gordonia is one of the mycolic acid-containing aerobic actinomycetes. This genus has 38 named species that are widespread in the natural environment; however, Gordonia species rarely cause human infections. A 76-year-old woman presented with cough and sputum for over 1 year and was suspected of having nontuberculous mycobacterial (NTM) lung disease. An NTM isolate from the sputum was initially identified as Mycobacterium lentiflavum or Mycobacterium genavense by genotypic identification targeting internal transcribed spacer (ITS). However, the isolate was finally confirmed as Gordonia otitidis by sequencing of 16S rRNA, gyrB and secA1 genes. In patients with suspected NTM lung disease, the etiologic agent might be an organism other than NTM such as G. otitidis but still be identified as NTM without sequencing of 16S rRNA or other genes. Especially in case that a possible NTM isolate is identified as M. lentiflavum or M. genavense by the genotypic method targeting ITS, additional genotypic tests such as sequencing of 16S rRNA and other genes would be necessary for more reliable identification.

In vitro antiviral activity of ribavirin against severe fever with thrombocytopenia syndrome virus

BACKGROUND/AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus. As yet, there is no effective antiviral therapy for SFTS. Ribavirin is a broad-spectrum antiviral agent, which has been tried for treatment of SFTS. In this study, antiviral activity of ribavirin against SFTSV has been investigated. METHODS: Vero cell-grown SFTSV strain Gangwon/Korea/2012 was treated with ribavirin at various concentrations. Antiviral activity of ribavirin was evaluated by inhibition of the SFTSV cytopathic effect in Vero cells and quantification of viral RNA load in culture supernatant using one-step real-time reverse transcription polymerase chain reaction. Cytotoxicity of ribavirin was determined by a tetrazolium-based colorimetric method. RESULTS: Ribavirin reduced SFTSV titers in a dose-dependent manner, with a half-maximal inhibitory concentration ranged from 3.69 to 8.72 μg/mL. Cytopathic effects were reduced as ribavirin concentration increased. No significant cytotoxicity was detected at ribavirin concentrations of ≤ 31.3 μg/mL. CONCLUSIONS: Ribavirin exhibited inhibitory activity against SFTSV replication in vitro, which suggests that ribavirin can be used as a potential antiviral agent for SFTS.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome in Southeastern Korea, 2015

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease characterized by fever, thrombocytopenia and diarrhea. SFTS was firstly reported in Korea in 2013 but its seroprevalence in the country has yet to be investigated. Here, we investigate the seroprevalence of SFTS in a Korean population. A cross-sectional study was conducted on patients who had their sera tested for various reasons at a tertiary university hospital on particular days in May 2015. This study was conducted in a tertiary hospital in southeastern Korea. Total antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM), specific to SFTS virus (SFTSV) in serum samples were detected by a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA). A total of 1,069 serum samples were tested. Median age was 59 years (range 12–96 years), and 51.5% were male. Overall, 22 patients (2.1%) were tested positive for anti-SFTSV antibodies. The SFTS seroprevalence increased significantly with age (P = 0.034). The seropositive rate of rural area was higher than that of urban area (7.7% vs. 1.9%, P = 0.040). Seropositive rates were not significantly different among underlying diseases. None of the antibody-positive patients showed typical symptoms or laboratory findings of SFTS at the time of sample collection. Results of real-time reverse transcription polymerase chain reaction (RT-PCR) were negative for all the seropositive patients. Our study shows 2.1% SFTS seroprevalence among the patients visiting a tertiary hospital in Korea. Seroprevalence is higher in older and rural population.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Predictors of Poor Retention in Care of HIV-infected Patients Receiving Antiretroviral Therapy in Korea: Five-Year Hospital-based Retrospective Cohort Study

Poor retention in care (RIC) is associated with higher antiretroviral therapy (ART) failure and worse survival. Identifying high risk patients for poor RIC is important for targeted intervention. A retrospective cohort study was conducted at a tertiary care hospital in Korea. HIV-infected patients initiating ART during 2002-2008 were included. 5 year-RIC was measured by hospital visit constancy (HVC) at 5 years after initiating ART. Among 247 enrolled patients, 179 (72.5%) remained in care, 20 (8.1%) were transferred to other hospitals, 9 (3.6%) died and 39 (15.8%) were lost to follow-up. We compared the demographic, psychosocial, and clinical characteristics between the groups with 100% HVC (n = 166, 67.2%) and 50; 95% confidence interval [CI] 1.10-15.15, P = 0.036), no non-HIV related comorbidity (OR 2.94 vs. comorbidity > or = 1; 95% CI 1.02-8.49, P = 0.046), baseline CD4 cell count > 300 cells/muL (OR 3.58 vs. < or = 200; 95% CI 1.33-9.65, P = 0.012) were significant predictable factors of poor RIC. HIV/AIDS care-givers should pay attention to young patients with higher baseline CD4 cell counts and no non-HIV related comorbidity.

Incidence and risk factors of hepatitis C virus infection among human immunodeficiency virus (HIV) patients in a large HIV clinic in South Korea

BACKGROUND/AIMS: Increasing incidences of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex were reported in the United States and Europe. However, few studies regarding the epidemiology of HCV infection in HIV-infected patients in Asian countries have been reported. METHODS: To determine the prevalence and incidence of HCV infection in HIV-infected patients, a retrospective cohort study was conducted. All HIV-infected patients who visited a tertiary care hospital in Korea from 2000 to 2013 were identified. Patients with ≥ 1 HCV antibody (Ab) test were included and observed until December 2014. RESULTS: Among 996 HIV-infected patients, 790 patients (79%) had baseline HCV Ab tests and 41 (5.2%) were positive at baseline and four at follow-up. Experience of injecting drug use (IDU; adjusted odds ratio, 16.20; 95% confidence interval [CI], 1.56 to 167.89; p < 0.01) was significantly associated with prevalent HCV infection. Conversion to HCV Ab positivity was observed in four of 384 included patients, with an incidence rate of 2.22 (95% CI, 0.60 to 5.80)/1,000 person-years (PYs); 164.89 (95% CI, 34.00 to 481.88)/1,000 PYs in patients with IDU, and 1.40 (95% CI, 0.35 to 7.79)/1,000 PYs in men who have sex with men who denied IDU. There was no significant increase in incidence rate of HCV in HIV-infected patients from 2009 to 2014 (p = 0.119). Among 19 patients who were positive for HCV RNA, genotype 1b (73%) was the most common following 2a/2c (20%). CONCLUSIONS: IDU was an independent risk factor for prevalent HCV infection. Prevalence of HCV infection was low and incidence of HCV infection was not significantly increased in HIV-infected patients in South Korea.

Prevalence and Clinical Impact of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolated From Hospitalized Patients

BACKGROUND: We estimated the prevalence and clinical impact of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). The concordance between macromethod and glycopeptide resistance detection (GRD) E tests was determined. In addition, predictors of clinical outcomes in hospitalized patients with S. aureus bacteremia (SAB) or pneumonia (SAP) were evaluated. METHODS: We obtained 229 consecutive S. aureus isolates from all hospitalized patients at two university hospitals located in Busan and Yangsan, Korea. Standard, macromethod, and GRD E tests were performed. Additionally, we reviewed the medical records of all patients. Among the 229 patients, predictors of clinical outcomes were analyzed for 107 patients with SAB and 39 with SAP. RESULTS: Among the 229 isolates, 34.5% of S. aureus isolates and 50.7% of methicillin-resistant S. aureus isolates exhibited the hVISA phenotype based on the macromethod E test. hVISA was nearly associated with treatment failure in patients with SAB (P=0.054) and was significantly associated with treatment failure in patients with SAP (P=0.014). However, hVISA was not associated with 30-day mortality in patients with SAB or SAP. The concordance between the macromethod and GRD E tests was 84.2%. CONCLUSIONS: hVISA is quite common in the southeastern part of Korea. hVISA is associated with treatment failure in patients with SAP.

A Case of Transverse Myelitis Caused by Varicella Zoster Virus in an Immunocompetent Older Patient / 감염과화학요법

Varicella zoster virus (VZV) is a human neurotropic alphaherpesvirus that causes chickenpox (varicella) in children. VZV reactivation may lead to neurological complications, including transverse myelitis. However, transverse myelitis caused by VZV reactivation is rare in immunocompetent patients. Herein, we report a case of transverse myelitis caused by VZV in an immunocompetent older patient, and confirmed this case by polymerase chain reaction. A 79-year-old woman visited our service with complaints of weakness in the right lower leg, generalized vesicular eruptions, and throbbing pain in the right flank for ten days. Spine MRI showed transverse myelitis in the thoracic spine at level T4–T11. The patient was treated with acyclovir and her neurological functions improved, except for sensory impairment below level T10. For older patients, early and aggressive antiviral treatment against VZV may be necessary even though these patients are immunocompetent.

The CD4 slope can be a predictor of immunologic recovery in advanced HIV patients: a case-control study

BACKGROUND/AIMS: Advanced human immunodeficiency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression. METHODS: A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA or = 500/mm3 at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation. RESULTS: Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes (cells/mm3 per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope > or = 20 during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery. CONCLUSIONS: The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients.

A Case of Pyogenic Spondylitis Due to Aggregatibacter aphrophilus / 대한임상미생물학회지

Aggregatibacter aphrophilus, a normal component of oral cavity flora, mostly causes infective endocarditis and only rarely causes spondylitis; no spondylitis cases have been previously reported in Korea. We report a case of pyogenic spondylitis due to A. aphrophilus without endocarditis. A 64-year-old man was admitted for back pain lasting 3 weeks. There was severe tenderness on lumbar spines but no fever. Laboratory evaluation showed leukocytosis and elevated C-reactive protein. Blood cultures were negative. Magnetic resonance imaging showed psoas abscess and vertebral inflammation. Pus was obtained by computerized tomography-guided aspiration from the psoas abscess and inoculated into blood culture bottles. After 5 days of incubation, growth was detected: the isolate was a Gram-negative short rod bacteria identified as A. aphrophilus by the automated system; this was confirmed by 16S ribosomal RNA sequencing. There was no evidence of endocarditis in echocardiography and retinal examination. Back pain persisted despite 8 weeks of antibiotic treatment, so vertebral corpectomy was performed. A. aphrophilus, a rare cause of pyogenic spondylitis, can induce spondylitis without endocarditis. If a patient with pyogenic spondylitis shows negative routine bacterial cultures, fastidious organisms such as A. aphrophilus should be suspected and the blood culture bottles could be used.

Severe Fever with Thrombocytopenia Syndrome / 대한내과학회지

Severe fever with thrombocytopenia syndrome (SFTS) is firstly reported in China in 2011. It is an emerging infectious disease in China, Japan and South Korea. It is caused by novel bunyavirus, called SFTS virus. The vector of SFTS is Haemaphysalis longicornis tick and domesticated animals may serve as intermediate hosts. The clinical manifestations of SFTS are fever, vomiting, diarrhea, thrombocytopenia and leukopenia. In severe cases, multiple organ failure, disseminated intravascular coagulopathy, and central nervous systems manifestation are present. The case-fatality rate is 6-30%. There is no effective antiviral therapy and supportive care is the main treatment.