Comparison of the Clinical Outcomes Between Early and Delayed Transplantation After SARS-CoV-2 Infection.

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

PPIB/Cyclophilin B expression associates with tumor progression and unfavorable survival in patients with pulmonary adenocarcinoma.

Cyclophilin B (CypB), encoded by peptidylprolyl isomerase B (PPIB), is involved in cellular transcriptional regulation, immune responses, chemotaxis, and proliferation. Recent studies have shown that PPIB/CypB is associated with tumor progression and chemoresistance in various cancers. However, the clinicopathologic significance and mechanism of action of PPIB/CypB in non-small cell lung cancer (NSCLC) remain unclear. In this study, we used RNA in situ hybridization to examine PPIB expression in 431 NSCLC tissue microarrays consisting of 295 adenocarcinomas (ADCs) and 136 squamous cell carcinomas (SCCs). Additionally, Ki-67 expression was evaluated using immunohistochemistry. The role of PPIB/CypB was assessed in five human NSCLC cell lines. There was a significant correlation between PPIB/CypB expression and Ki-67 expression in ADC (Spearman correlation r=0.374, P<0.001) and a weak correlation in SCC (r=0.229, P=0.007). In ADCs, high PPIB expression (PPIBhigh) was associated with lymph node metastasis (P=0.023), advanced disease stage (P=0.014), disease recurrence (P=0.013), and patient mortality (P=0.015). Meanwhile, high Ki-67 expression (Ki-67high) was correlated with male sex, smoking history, high pT stage, lymph node metastasis, advanced stage, disease recurrence, and patient mortality in ADC (all P<0.001). However, there was no association between either marker or clinicopathological factors, except for old age and PPIBhigh (P=0.038) in SCC. Survival analyses revealed that the combined expression of PPIBhigh/Ki-67high was an independent prognosis factor for poor disease-free survival (HR 1.424, 95% CI 1.177-1.723, P<0.001) and overall survival (HR 1.266, 95% CI 1.036-1.548, P=0.021) in ADC, but not in SCC. Furthermore, PPIB/CypB promoted the proliferation, colony formation, and migration of NSCLC cells. We also observed the oncogenic properties of PPIB/CypB expression in human bronchial epithelial cells. In conclusion, PPIB/CypB contributes to tumor growth in NSCLC, and elevated PPIB/Ki-67 levels are linked to unfavorable survival, especially in ADC.

Viral and Immunologic Factors Associated with Fatal Outcome of Patients with Severe Fever with Thrombocytopenia Syndrome in Korea.

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

Frequency of putative enteric zoster diagnosed using saliva samples in patients with abdominal pain: a prospective study.

BACKGROUND: Varicella-zoster virus (VZV) infects and establishes latency in neurons in the ganglia of the cranial nerve, dorsal root and enteric ganglia. VZV reactivation in enteric neurons (enteric zoster) can cause non-specific abdominal pain and/or serious gastrointestinal dysfunction without cutaneous manifestations. Detection of VZV DNA in saliva may be useful for identifying enteric zoster. We evaluated the frequency of putative enteric zoster based on the presence of salivary VZV DNA in patients with acute abdominal pain. METHODS: Adult patients who visited the emergency room due to moderate to severe acute abdominal pain were prospectively enrolled at a tertiary hospital between May 2019 and November 2019. Abdominopelvic computed tomography (APCT) was performed in all patients. We also evaluated the presence of salivary VZV DNA in patients with confirmed coronavirus disease-19 (COVID-19) who were under stressful conditions. Saliva samples were collected from all studied patients. Enteric zoster was suspected based on the presence of salivary VZV DNA, detected using real-time polymerase chain reaction (PCR). RESULTS: Fifty patients with moderate to severe abdominal pain were enrolled. Five of 50 patients exhibited positive VZV-DNA PCR results. APCT revealed that among these five patients, two had pancreatic head cancer, two had small bowel obstruction after intra-abdominal surgery, and one had no remarkable findings. However, all 14 patients with COVID-19 showed negative salivary VZV-DNA PCR results. CONCLUSIONS: Approximately 10% of patients with moderate to severe acute abdominal pain showed positivity for salivary VZV DNA. Further studies are warranted on whether antiviral therapy based on salivary VZV-DNA PCR results may relieve abdominal pain in the studied patient population. TRIAL REGISTRATION: clinicaltrial.gov, number NCT03862092.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection.

BACKGROUND: Asymptomatic individuals with SARS-CoV-2 infection have viable viral loads and have been linked to several transmission cases. However, data on the viral loads in such individuals are lacking. We assessed the viral loads in asymptomatic individuals with SARS-CoV-2 infection in comparison with those in symptomatic patients with COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients with mild COVID-19 in South Korea. The presence of symptoms was evaluated with a questionnaire-based survey. Viral loads in the upper respiratory tract were measured with real-time reverse transcription-PCR (RT-PCR) targeting the E, RdRp and N genes of SARS-CoV-2, with a cycle threshold (Ct) value of 40 for determining positivity. RESULTS: In 213 patients with SARS-CoV-2 infection, 41 (19%) had remained asymptomatic from potential exposure to laboratory confirmation and admission; of them, 39 (95%) underwent follow-up RT-PCR testing after a median 13 days. In 172 symptomatic patients, 144 (84%) underwent follow-up RT-PCR testing. Twenty-one (54%) asymptomatic individuals and 92 (64%) symptomatic patients tested positive for SARS-CoV-2 at follow-up. Asymptomatic individuals and symptomatic patients did not show any significant differences in the mean Ct values of the E (31.15 vs 31.43; p>0.99), RdRp (32.26 vs 32.93; p=0.92) and N (33.05 vs 33.28; p>0.99) genes. CONCLUSION: Approximately one-fifth of the individuals without severe symptoms were asymptomatic, and their viral loads were comparable to those in symptomatic patients. A large proportion of mildly symptomatic patients with COVID-19 or asymptomatic individuals with SARS-CoV-2 showed persistent positive upper respiratory RT-PCR results at follow-up.

Kinetics of Serological Response in Patients with Severe Fever with Thrombocytopenia Syndrome.

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

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

OBJECTIVES: The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. MATERIALS AND METHODS: A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. RESULTS: Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. CONCLUSIONS: The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.

Clinical characteristics and outcomes of Staphylococcus aureus bacteremia from a biliary source.

Staphylococcus aureus is a virulent gram-positive organism, which rarely involves the biliary tract. This study aimed to analyze the clinical characteristics and outcomes of S. aureus bacteremia (SAB) originating from the biliary tract by comparing them with those of catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. A matched case-control study within a prospective observational cohort of patients with SAB was conducted. Biliary SAB was defined as the isolation of S. aureus from blood cultures with symptoms and signs of biliary infection. Biliary SAB patients were matched (1:3) with the control groups: patients with catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. Out of 1818 patients with SAB enrolled in the cohort, 42 (2%) had biliary SAB. Majority of these patients had solid tumors involving the pancreaticobiliary tract or liver, biliary drainage stent, and/or recent broad-spectrum antibiotic exposure. Patients with biliary SAB were more likely to have community-onset SAB, solid tumors, and lower APACHE II score than those with catheter-related SAB. They were less likely to have community-acquired infection and solid tumors and more likely to have lower Charlson comorbidity index and higher APACHE II score as compared with biliary K. pneumoniae bacteremia. The 12-week mortality in the biliary SAB group was higher than those in other control groups (60% vs. 20% and 14%). After adjusting for confounding factors, biliary SAB was independently associated with higher mortality. Biliary SAB is relatively rare. When it is clinically suspected, early aggressive treatment should be considered due to high mortality.

Coinfection of Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in Patients with Tick-Borne Illness.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are the most common tick-borne diseases in South Korea. However, few studies have systematically examined the simultaneous presence of the two diseases. We found that two (4.9%) of 41 patients with suspected and confirmed SFTS had evidence of coinfection with scrub typhus. In addition, two (3.6%) of 55 suspected and confirmed scrub typhus patients were identified to have coinfection with SFTS. Our data suggest that diagnostic evaluation for coinfection in patients with tick-borne illness and empirical doxycycline treatment in patients with SFTS may be warranted in areas endemic for both diseases until coinfection with scrub typhus is ruled out.