Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center:A Preliminary Result of Randomized Controlled Trial

Background@#This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). @*Materials and Methods@#A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. @*Results@#Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. @*Conclusion@#In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

Performance Evaluation of TaqMan Probe Method for BK Virus DNA Quantification by Real-time Polymerase Chain Reaction / 대한임상미생물학회지

BACKGROUND: We evaluated the performance of a newly developed real-time polymerase chain reaction (PCR) method using TaqMan probe (TP) and internal control (IC) for quantitation of BK virus (BKV) DNA. METHODS: PCR primers and TP were targeted for the VP1 of BKV and 300 bp-region of VP1 was cloned to prepare a standard DNA. Threshold cycles (Ct) of IC was set at 33+/-3. The recovery rates, precision, linearity, and limit of detection (LOD) were measured using the standard DNA. To correlate TP with previous hybridization probe (HP) method, Ct of those were compared using 35 HP-positive and 15 HP-negative specimens, and the interpretation agreement was analyzed in 63 consecutive clinical specimens including 32 urines and 31 plasmas. Fifty-three53 specimens measured for IC were analyzed for positive rates and levels of BKV according to Ct of IC. RESULTS: The average recovery rate was 101.1% and intra-assay and inter-assay coefficiency variations were 0.017~0.059 and 0.036, respectively, with the specimens of 3 log/mL, and 0.041~0.063 and 0.045, respectively, with the specimens of 6 log/mL. LOD was 183 copies/mL and linearity range was 2.7 log- 12 log/mL. Ct of TP were correlated with those of HP with the function of y=0.8912x+0.3164 (R2=0.9062). Among 63 clinical specimens, 16 were positive in TP and 12 were positive in HP with an agreement of 90.4%. Ct of IC were over 36 in 31 specimens (22 urines and 9 plasmas), of which BKV DNA was much higher in 7 (22.5%) BKV-positive specimens (5.9+/-1.7 log/mL) than in 4 (18.1%) BKV-positive specimens (3.9+/-1.0 log/mL) of 22 having Ct of IC < or =36.; 5.9+/-1.7 vs. 3.9+/-1.0 log/mL. CONCLUSION: TP warrants to be a reliable method for quantification of BKV. IC seemed to be essential to differentiate false-negative results or underestimation of BKV in clinical specimens, especially in urine.

A Case of Erythromycin-Resistant Ureaplasma urealyticum Meningitis in a Premature Infant / 대한진단검사의학회지

Ureaplasma urealyticum causes infection or colonization of female genital tracts associated with preterm delivery and infertility and the infection of the bloodstream, respiratory tract, and central nervous system in infants, especially in prematures. We report the first case of U. urealyticum meningitis in a premature infant in Korea. She was born with a birth weight of 1,481 gram at 32+3 weeks' gestation and hospitalized for a respiratory care in the NICU in November 2005. Endotracheal aspirates and urine cultures grew U. urealyticum at or = 10(4) CFU/mL of CSF. The patient had a marked CSF pleocytosis, low glucose and high protein content on the 13th hospital day. CSF cultures for ordinary bacteria, mycobacteria and fungi remained negative. U. urealyticum was resistant to erythromycin, tetracycline, ciprofloxacin and pristinamycin, but susceptible to doxycycline. Although she was treated with erythromycin for 30 days, the organism was still isolated four times from the CSF with fluctuation of C-reactive protein (CRP). After the addition of chloramphenicol, CSF cultures became negative in 3 days. However, CRP rose again with increased BUN at the 99th hospital day, and she died on the 103rd hospital day under the diagnosis of a clinical sepsis of unknown origin. In acute meningitis of prematures already colonized with U. urealyticum, ureaplasmal cultures and susceptibility test are warranted in Korea.

Reproducibility of Total T Lymphocyte and Characterization of CD3(+)/CD4(-)/CD8(-) Lymphocyte in T Lymphocyte Subset Assay / 대한임상병리학회지

BACKGROUND: Total T lymphocytes can be measured by CD3-fluorescein isothiocyanate (FITC)/CD4-phycoerythrin (PE) and CD3-FITC/CD8-PE. The difference in the CD3 percentages between these two determinations was evaluated. And, we characterized the CD3(+)CD4(-)CD8(-) T lymphocytes subset using the monoclonal antibody that detects gamma delta T lymphocytes receptors. METHODS: The T lymphocyte subset assay was performed on 221 samples. A two-color direct immunofluorescence flow cytometric assay was done using a Simultest IMK-Lymphocyte kit (Bec-ton- Dickinson, San Jose, CA, USA). If the difference between the CD3 determinations were greater than 3%, the entire procedure was reviewed and the flow cytograms were reanalyzed. In 71 among 221 samples the proportion of gamma delta T lymphocytes was determined. RESULTS: The difference between the CD3-FITC/CD4-PE tube and CD3-FITC/CD8-PE tube was 3.0%, 3.6%, 3.0%, 3.4%, and 2.4% in normal subjects, patients with chronic liver disease, patients with cancer, patients with other diseases, and children, respectively. The between-tube differences for CD3 exceeding 3% were found in 69 samples (31.2%). The proportion of gamma delta T lymphocytes was 0.81%, 2.46%, 2.50%, and 0.85% in normal controls, patients with chronic liver disease, patients with cancer and patients with other diseases, respectively. No correlation between gamma delta T lymphocytes and CD3(+)CD4(-)CD8(-) T lymphocytes was observed. CONCLUSIONS: The reproducibility of the total T lymphocytes should be improved because of the between-tube difference exceeding 3% in about one third of the cases. Additionally, CD3(+)CD4(-)CD8(-) T lymphocytes were composed of heterogeneous subsets including gamma delta T lymphocytes and their proportion might be considered to be related to individual variation.

An Enterococcus gallinarum Strain Carrying Both vanA and vanC1 Genes / 대한임상병리학회지

Enterococcus gallinarum carrying both vanA and vanC1 genes were detected from a surveillance culture from a patient staying at the surgical intensive care unit for a few years. E. gallinarum, SI04, was highly resistant to vancomycin (MIC of >or=256ng/mL) and teicoplanin (MIC of >or=256ng/mL). Multiplex PCR for vanA, vanB, vanC1 and vanC2/3 genes revealed SI04 to be positive for both vanA and vanC1 genes. This finding supports the fact that genotyping is needed to classify vancomycin-resistant enterococci (VRE). This is the first report on VanC VRE accompanying vanA gene in Korea.

Nocardiosis Following Renal Transplantation / 대한이식학회지

PURPOSE: Infection with Nocardia species is an uncommon yet important cause of morbidity and mortality in renal transplant recipients. METHODS: We experienced 6 cases of nocardiosis among 239 renal transplant recipients maintained on tacrolimus- or cyclosporine-based immunosuppression from May 1999 to February 2001. RESULTS: All the six patients had pulmonary nocardiosis from 36 to 220 (mean 82) days after renal transplantation. Due to a multiplicity of infection sites, cerebral abscess was detected in 2 patients, soft tissue abscess in 2, allograft abscess in 1 and subretinal abscess in 1. Comparing the routine trimethoprim/ sulfamethoxazole (TMP/SMX) prophylaxis after transplantation, 5 out of 6 patients took TMP/SMX for a mean of 1.8 months due to an increased AST/ALT. All the cases required invasive diagnostic procedures such as percutaneous needle aspiration (PC NA) or stereotactic aspiration. In the antimicrobial susceptibility test, isolates were sensitive to TMP/SMX, amikacin and imipenem. In the early stage of infection, we used triple chemotherapy (TMP/SMX, amikacin, imipenem) for cerebral nocardiosis and dual therapy (TMP/SMX, amikacin) for localized pulmonary infection. There were no mortality and all the graft maintained stable function. CONCLUSION: After organ transplantation, pneumonia accompanied with satellite soft tissue infection should be considered as a nocardiosis. Pro- phylactic use of TMP/SMX is crucial for effective prevention of nocardiosis.

Necessity of Anti-HBc and Anti-HBs Screening in Korean Blood Donation Program: Study using LG Anti-HBc and LG Anti-HBs ELISA Kit and HBV Nucleic Acid Amplification Test / 대한수혈학회지

BACKGROUND: Post-transfusion hepatitis B remains a risk for recipients of HBsAg negative bloods in Korea. The usefulness of anti-HBc screening for blood donors to reduce the risk of HBV transmission was evaluated in this study using LG Anti-HBc and LG Anti-HBs ELISA (LG Chemicals, Seoul, Korea) and HBV nucleic acid amplification test. METHOD: Sera from 2,274 HBsAg-negative blood donors were tested of anti-HBc and anti-HBs by LG Anti-HBc and LG Anti-HBs ELISA, respectively. Using 260 samples from HBsAg-negative blood donors and 62 FANA-positive samples, reactivity to LG Anti-HBc ELISA were compared with COBAS CORE Anti-HBc EIA (Roche Diagnostics, Basel, Switzerland). The precision of LG Anti-HBc was also tested. The nucleic acid amplification of 97 primary pools prepared from 2,274 samples was carried out, and then HBV presence was confirmed in individual samples. RESULT: Of 2,274 HBsAg-negative blood donors, 531 (23.4%) were positive for anti-HBc and 32 (1.4%) were anti-HBc positive/ anti-HBs negative. The concordance rate of LG Anti-HBc ELISA and COBAS was 97.8% (315/322). The intra-run and inter-run coefficient of variation was 4.7-10.2% and 2.5-11.4%, respectively. Thirteen pools showed initial positive in HBV PCR, but seven pools (53.8%) were finally found to be false positive. Of six true positive pools, seven samples were confirmed to have HBV DNA. The HBV detection rate was 6.3% (2/32) among donors whose results were anti-HBc positive/ anti-HBs negative. CONCLUSION: Among screen-negative blood donors, 6.3% of donors whose seroreactivity was anti-HBc positive/ anti-HBs negative were positive for HBV by nucleic acid amplification test, while donors showing such seroreactivity were only 1.4%. It is suggested that an introduction of anti-HBc and anti-HBs testing in Korean Blood Donation program be efficient to attain safety from HBV transmission.

Detection of resistance mutation to lamivudine in HIV-1 infected patients

To investigate resistance to lamivudine (3TC), we examined the incidence of M184V in 20 HIV-1 patients treated with 3TC for 13.1 +/- 9 months. Fourteen of 20 patients had been exposed to zidovudine (ZDV) or didanosine (ddl) prior to 3TC therapy. Nested PCR targeting to reverse transcriptase (RT) and direct sequencing were performed for peripheral blood mononuclear cells sampled serially. There were resistance mutations to ZDV in at least 9 patients at baseline, although there was no resistance mutation to 3TC. We could detect M184V in 6 (30%) out of 20 patients. The incidence of M184V increased as the duration of therapy prolongs (13% in samples<12 months; 47% in samples gtoreq 12 months). The frequency of mutation M184V was higher in patients with previous mutation to ZDV than in patients with wild type. Resistance mutation was not detected in 7 patients. This study shows that resistance to 3TC tends to develop rapidly in patients with baseline mutations or two drugs combination therapy than in those treated simultaneously with triple drugs. This report is the first on resistance to 3TC in Korean AIDS patients.

Detection of Mutations to Zidovudine in the pol Gene of Human Immunodeficiency Virus-1 by Direct Sequencing

No abstract available.