Comparison of Xpert Xpress SARS-CoV-2 Assay Compared with Standard M nCoV Real-Time PCR: Prospective Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be diagnosed using rapid real-time polymerase chain reaction (PCR), real-time reverse transcription PCR (rRT-PCR), or rapid antigen testing. Among these, rRT-PCR is considered the gold standard assay. The Xpert Xpress SARS-CoV-2 assay is a rapid, real-time PCR test; approved by the Korean Disease Control and Prevention Agency in 2020. Current performance of the Xpert assay (Xpert) with the STANDARD M nCoV Real-Time Detection kit (SD) were determined. METHODS: All samples used by the SD test team were immediately transferred to the Xpert test team within 24 hours. Both tests were conducted between April 2023 and July 2023. Exclusion criteria were studies which show either inconclusive, invalid, or erroneous results. Positive rate, sensitivity, specificity, overall concordance rate, positive concordance rate, discordance rate, false-positive rate, and false-negative rates of the Xpert assay with the STANDARD M nCoV Real-Time Detection kit were determined. RESULTS: Samples from 347 patients (174 men and 173 women) with a median age of 60 years (range; 6 - 90 years) were included. Positive rate, sensitivity, specificity, overall concordance rate, positive concordance rate, discordance rate, false-positive rate, and false-negative rates of the Xpert assay were 11.2%, 82.1%, 95.0%, 93.9%, 6.6%, 6.1%, 41.0%, and 1.6%, respectively. CONCLUSIONS: COVID-19 results from Xpert should be confirmed through rRT-PCR because of low sensitivity (82.1%) and high false-positive rate (41.0%).

Clinical Characteristics of COVID-19: Use of Steroids in Mostly Unvaccinated COVID-19 Patients Before the Omicron Variant.

BACKGROUND: Glucocorticoids are one of the current standard agents for moderate to severe coronavirus disease 2019 (COVID-19) treatment based on the RECOVERY trial. Data on the real clinical application of steroids for COVID-19 are scarce and will help guide the optimal use of steroids. We described the current prescription pattern of steroids for COVID-19 and investigated the factors related to specific practices. METHODS: All adults aged ≥ 19 years who were diagnosed with COVID-19 by real-time reverse transcription-polymerase chain reaction and admitted to one of 3 study hospitals from 8 December 2020 to 30 June 2021 were enrolled. Demographic and clinical data, including medications and oxygen therapy, were retrospectively collected from electronic medical records. The severity of comorbidities and COVID-19 were measured. The subjects were divided into steroid and nonsteroid groups, and the steroid group was then subdivided into standard and higher/longer groups. RESULTS: Among a total of 805 patients, 217 (27.0%) were treated with steroids. The steroid group showed a higher rate of oxygen therapy (81.1% vs. 2.7%), more concomitant use of remdesivir (77.4% vs. 1.4%) or antibiotics (79.3% vs. 4.3%), and a higher proportion of high risk according to National Early Warning Score-2 score (30.0% vs. 0.9%) or severe risk according to National Institute of Allergy and Infectious Disease Ordinal Scale score (81.1% vs. 2.7%) than the nonsteroid group. The mortality of the steroid group was 4.6%. In the steroid group, 82.5% received a standard or lower dose of steroids within ten days, and 17.5% (38/217) received a higher or longer dose of steroids. Multivariate analysis showed that initial lymphopenia (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89-0.99) and high level of lactate dehydrogenase (LDH) (aOR, 1.00; 95% CI, 1.00-1.01) were independent risk factors for higher doses or longer steroid use. CONCLUSION: The dose and duration of steroids were in line with current guidelines in 82.5% of COVID-19 patients, but the outliers may need tailored therapy according to surrogate markers, such as initial lymphopenia or high level of LDH.

Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection.

Waning humoral immunity in coronavirus disease patients has raised concern over usefulness of serologic testing. We investigated antibody responses of 58 persons 8 months after asymptomatic or mildly symptomatic infection with severe acute respiratory syndrome coronavirus 2. For 3 of 4 immunoassays used, seropositivity rates were high (69.0%-91.4%).

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.

Clinical Characteristics of COVID-19: Risk Factors for Early Oxygen Requirement after Hospitalization.

BACKGROUND: Some coronavirus disease 2019 (COVID-19) patients initially present with early oxygen demand, requiring more medical resources, and some develop severe conditions, while others worsen later in their clinical course. Whether the nature of the two groups is the same but in the spectrum of different diagnostic time points is not certain. METHODS: Hospitalized COVID-19 patients who needed oxygen therapy from February to November 2020 were included in the study. The patients were divided into early and late groups based on the time when the oxygen requirement occurred. Basic and epidemiologic characteristics were compared. Clinical variables were analyzed in both groups. RESULTS: A total of 164 patients needed oxygen therapy, 94 of whom were in the early group and 70 of whom were in the late group. The early and late groups had similar baseline characteristics except age (median age, 73 vs. 67 years), uncertain exposure history (50% vs. 31.4%) and the time from the onset of illness to admission (median, 5 vs. 2 days). Multivariate analysis showed that age > 65 years (OR, 4.65), symptom onset > 5 days (OR, 9.13) and several clinical manifestations, such as febrile sensation (OR, 6.01), dyspnea (OR, 30.0), C-reactive protein > 1 mg/dL (OR, 7.87) and chest X-ray abnormality (OR, 8.15), were predictive factors in the early group. The early group required more intensive care such as mechanical ventilation care, extracorporeal membrane oxygenation and death (29.8% vs. 14.3%, P = 0.002). CONCLUSION: Older age, especially > 65 years, and a delay of over 5 days from the onset of illness to admission were associated with early oxygen demand in COVID-19 patients. Interventions for earlier diagnosis of elderly people may benefit clinical outcomes.

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 syndrome-coronavirus-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 to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients.

We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.

Prevalence of cryptococcal antigenemia in hospitalized patients with liver cirrhosis.

The benefits of screening for cryptococcal antigenemia and of preemptive antifungal treatment in HIV-infected patients have been proven. Liver cirrhosis is an important risk factor for cryptococcal infections. Cryptococcal infections are rapidly fatal in patients with liver cirrhosis, especially when diagnosis is delayed. However, screening for cryptococcal antigenemia has not been investigated in these patients. The aim of this study was to investigate the prevalence of cryptococcal antigenemia in hospitalized patients with liver cirrhosis. This prospective study was conducted at Seoul National University Hospital from July 2017 to January 2018. We included patients with liver cirrhosis who were admitted regardless of symptoms or signs suggesting cryptococcal infections. The severity of cirrhosis was evaluated from Child-Pugh and model for end-stage liver disease (MELD) scores. Serum cryptococcal antigenemia was determined using a latex agglutination test. A total of 294 patients were included in the analysis, comprising 104 (35.4%), 100 (34.0%), and 90 (30.6%) patients in Child-Pugh classes A, B, and C, respectively. There were 21 cases of spontaneous bacterial peritonitis, and 14 of hepatic encephalopathy, but none of cryptococcal peritonitis or meningitis. In addition, none of the patient specimens tested positive in the serum cryptococcal latex agglutination test (one-sided 97.5% confidence interval, 0% ∼ 1.2%). Liver cirrhosis is a major risk factor for cryptococcal infections, but the prevalence of serum cryptococcal antigen positivity in patients with liver cirrhosis is very low. Therefore, screening for cryptococcal antigenemia and preemptive antifungal treatment in cirrhotic patients might not be beneficial.

Clinical Characteristics of COVID-19: Clinical Dynamics of Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection Detected by Early Active Surveillance.

BACKGROUND: There is limited information describing the presenting characteristics and dynamic clinical changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosed in the early phase of illness. This study is a case series of patients with coronavirus disease 2019 (COVID-19) admitted to 11 hospitals in Korea. METHODS: Patients with confirmed SARS-CoV-2 infection by positive polymerase chain reaction (PCR) testing of respiratory specimens by active surveillance that were finally discharged between February 20 and April 30, 2020 were included. Patients were classified into mild and non-mild groups on initial admission according to oxygen demand and Sequential Organ Failure Assessment score, and the mild group was followed up and subgrouped into non-aggravation and aggravation groups. RESULTS: A total of 161 patients with SARS-CoV2 infection were enrolled. Among the mild group of 136 patients, 11.7% of patients experienced clinical aggravation during hospitalization, but there was no initial clinical parameter on admission predicting their aggravation. Fever (odds ratio [OR], 4.56), thrombocytopenia (OR, 12.87), fever (OR, 27.22) and lactate dehydrogenase (LDH) > 300 U/L (OR, 18.35), and CRP > 1 mg/dL (OR, 11.31) significantly indicated aggravation in the 1st, 2nd, 3rd, and 4th 5-day periods, respectively. PCR positivity lasted for a median of 22 days and 32 days after the onset of illness in the non-aggravation and aggravation groups, respectively. CONCLUSION: Old age was associated with early severe presentation. Clinical aggravation among asymptomatic or mild patients could not be predicted initially but was heralded by fever and several laboratory markers during the clinical course.

The Genetic Polymorphism UGT1A4*3 Is Associated with Low Posaconazole Plasma Concentrations in Hematological Malignancy Patients Receiving the Oral Suspension.

The metabolism of posaconazole is mediated mainly by uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, especially UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the posaconazole plasma concentration (PPC). This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three times daily for fungal prophylaxis. The patients were examined for the multidrug resistance gene 1 3435C>T and 2677G>T/A variations and the UGT1A4*3 allele by direct sequencing of DNA from peripheral whole-blood samples. We defined poor absorbers to be those with PPCs of <200 ng/ml and the optimal PPC to be ≥700 ng/ml on day 8. The associations between genetic polymorphisms and the PPC were evaluated using multivariate logistic regression analysis including clinical variables. During the study period, 132 patients were enrolled. Six patients (4.5%) were defined as poor absorbers, and 49 patients (37.1%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for a poor absorber were at least one UGT1A4*3 allele (adjusted odds ratio [aOR], 18.81; 95% confidence interval [CI], 1.09 to 324.44; P = 0.043) and poor oral food intake (aOR per -100 kcal, 1.44; 95% CI, 1.04 to 1.99; P = 0.029). There was no statistically significant association between the genetic polymorphisms and achievement of the optimal PPC on day 8. The UGT1A4*3 polymorphism is an independent risk factor for being a poor absorber of posaconazole oral suspension in patients with hematological malignancies.

Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients With Hematologic Malignancies.

BACKGROUND: Therapeutic drug monitoring (TDM) of posaconazole is usually performed 1 week after starting the drug because of its long half-life. However, previous studies showed that measuring the posaconazole plasma concentration (PPC) on day 3 is effective for predicting steady-state levels. The purpose of this study was to evaluate the relevance of early TDM (day 3) of posaconazole for achieving an optimal PPC. METHODS: This prospective study was conducted from September 2014 to August 2016. A total of 148 patients with acute myeloid leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral suspension 3 times daily for fungal prophylaxis. During the period from September 2014 to December 2015 (control group), no dose adjustment was performed on day 3. During the period from January 2016 to Aug 2016 (early TDM group), the frequency of posaconazole 200-mg administration was increased to 4 times daily in patients whose PPC on day 3 was <400 ng/mL. The cutoff value for optimal PPC on day 8 was defined as 500 ng/mL. RESULTS: In 21 of 107 patients (20%) in the control group, PPC was <400 ng/mL on day 3. In 15 (71%) of these 21 patients, the PPC was suboptimal on day 8. In the early TDM group, the PPC was <400 ng/mL on day 3 in 4 of 41 patients (10%). After increasing the posaconazole administration frequency in these 4 patients, PPC was suboptimal on day 8 in 1 patient (25%). In both groups, 104 patients had a PPC of ≥500 ng/mL on day 3, but 7% (7/104) of these had a suboptimal level on day 8. CONCLUSIONS: Early TDM on day 3 for posaconazole suspension may help more patients achieve optimal drug levels on day 8, although TDM on day 8 is needed even in patients with optimal levels on day 3.

Association of arterial stiffness with aortic calcification and tortuosity.

Impact of arterial stiffness on aortic morphology has not been well evaluated. We sought to investigate the association of brachial-ankle pulse wave velocity (baPWV) with aortic calcification and tortuosity.A total of 181 patients (65.4 ±â€Š10.4 years, males 59.7%) who underwent computed tomographic angiography and baPWV measurement within 1 month of study entry were retrospectively reviewed. Aortic calcification was quantified by the calcium scoring software system. Aortic tortuosity was defined as the length of the midline in the aorta divided by the length of linear line from the aortic root to the distal end of the thoraco-abdominal aorta. In simple correlation analyses, baPWV was correlated with aortic calcification (r = 0.36, P < .001) and tortuosity (r = 0.16, P = .030). However, these significances disappeared after controlling for confounders in multivariate analyses. Factors showing an independent association with aortic calcification were age (ß = 0.37, P < .001), hypertension (ß = 0.19, P = .003), diabetes mellitus (ß = 0.12, P = .045), smoking (ß = 0.17, P = .016), and estimated glomerular filtration rate (ß = -0.25, P = .002). Factors showing an independent association with aortic tortuosity were age (ß = 0.34, P < .001), body mass index (ß = -0.19, P = .018), and diabetes mellitus (ß = -0.21, P = .003).In conclusion, baPWV reflecting arterial stiffness was not associated with aortic calcification and tortuosity. Traditional cardiovascular risk factors were more influential to aortic geometry. Further studies with a larger sample size are needed to confirm our results.

A Risk-Scoring System for Predicting Methicillin Resistance in Community-Onset Staphylococcus aureus Bacteremia in Korea.

AIMS: We aimed to develop a simple scoring system to predict risk for methicillin resistance in community-onset Staphylococcus aureus bacteremia (CO-SAB) by identifying the clinical and epidemiological risk factors for community-onset methicillin-resistant S. aureus (MRSA). METHODS: We retrospectively analyzed data from three multicenter cohort studies in Korea in which patient information was prospectively collected and risk factors for methicillin resistance in CO-SAB were identified. We then developed and validated a risk-scoring system. RESULTS: To analyze the 1,802 cases of CO-SAB, we included the four most powerful predictors of methicillin resistance that we identified in the scoring system: underlying hematologic disease (-1 point), endovascular infection as the primary site of infection (-1 point), history of hospitalization or surgery in ≤1 year (+0.5 points), and previous isolation of MRSA in ≤6 months (+1.5 points). With this scoring system, cases were classified into low (less than -0.5), intermediate (-0.5-1.5), and high (≥1.5) risk groups. The proportions of MRSA cases in each group were 24.7% (22/89), 39.0% (607/1,557), and 78.8% (123/156), respectively, and 16.7% (1/6), 33.8% (112/331), and 76.9% (10/13) in a validation set. CONCLUSIONS: This risk-scoring system for methicillin resistance in CO-SAB may help physicians select appropriate empirical antibiotics more quickly.

Comparison of Plasma Concentrations of Posaconazole with the Oral Suspension and Tablet in Korean Patients with Hematologic Malignancies.

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.