Targeted Versus Shotgun Metagenomic Sequencing-based Detection of Microorganisms in Sonicate Fluid for Periprosthetic Joint Infection Diagnosis.

BACKGROUND: Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly. Here, 16S ribosomal RNA (rRNA) gene-based targeted metagenomic sequencing (tNGS) was compared to sNGS of sonicate fluid for microbial detection and identification in patients with total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure. METHODS: A convenience sample of sonicate fluids derived from patients who had undergone THA or TKA removal, enriched with culture negative PJI cases, was tested. Samples had been previously tested by sNGS. For tNGS, samples were extracted, amplified by polymerase chain reaction targeting the V1 to V3 regions of the 16S rRNA gene, and sequenced on an Illumina MiSeq. RESULTS: A total of 395 sonicate fluids, including 208 from subjects with PJI, were studied. Compared with sonicate fluid culture, tNGS had higher positive percent agreement (72.1 vs 52.9%, P < .001), detecting potential pathogens in 48.0% of culture-negative PJIs. There was no difference between the positive percent agreement of tNGS (72.1%) and sNGS (73.1%, P = .83). CONCLUSIONS: 16S rRNA gene-based tNGS is a potential diagnostic tool for PJI pathogen identification in sonicate fluid from failed THAs and TKAs in culture-negative cases, with similar performance characteristics to sNGS.

Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice.

Acute kidney injury (AKI) is a common complication of sepsis. Eupatilin (EUP) is a natural flavone with multiple biological activities and has beneficial effects against various inflammatory disorders. However, whether EUP has a favorable effect on septic AKI remains unknown. Here, we examined the effect of EUP on lipopolysaccharide (LPS)-evoked AKI in mice. LPS-evoked renal dysfunction was attenuated by EUP, as reflected by reductions in serum creatinine and blood urea nitrogen levels. LPS injection also induced structural damage such as tubular cell detachment, tubular dilatation, brush border loss of proximal tubules, and upregulation of tubular injury markers. However, EUP significantly ameliorated this structural damage. EUP decreased serum and renal cytokine levels, prevented macrophage infiltration, and inhibited mitogen-activated protein kinase and NF-κB signaling cascades. Lipid peroxidation and DNA oxidation were increased after LPS treatment. However, EUP mitigated LPS-evoked oxidative stress through downregulation of NPDPH oxidase 4 and upregulation of antioxidant enzymes. EUP also inhibited p53-mediated apoptosis in LPS-treated mice. Therefore, these results suggest that EUP ameliorates LPS-evoked AKI through inhibiting inflammation, oxidative stress, and apoptosis.

16S rRNA Gene PCR/Sequencing of Heart Valves for Diagnosis of Infective Endocarditis in Routine Clinical Practice.

Sequencing is increasingly used for infective endocarditis (IE) diagnosis. Here, the performance of 16S rRNA gene PCR/sequencing of heart valves utilized in routine clinical practice was compared with conventional IE diagnostics. Subjects whose heart valves were sent to the clinical microbiology laboratory for 16S rRNA gene PCR/sequencing from August 2020 through February 2022 were studied. A PCR assay targeting V1 to V3 regions of the 16S rRNA gene was performed, followed by Sanger and/or next-generation sequencing (NGS) (using an Illumina MiSeq), or reported as negative, depending on an algorithm that included the PCR cycle threshold value. Fifty-four subjects, including 40 with IE, three with cured IE, and 11 with noninfective valvular disease, were studied. Thirty-one positive results, 11 from NGS and 20 from Sanger sequencing, were generated from analysis of 16S rRNA gene sequence(s). Positivity rates of blood cultures and 16S rRNA gene PCR/sequencing of valves were 55% and 75%, respectively (P = 0.06). In those with prior antibiotic exposure, positivity rates of blood cultures and 16S rRNA gene PCR/sequencing of valves were 11% and 76%, respectively (P < 0.001). Overall, 61% of blood culture-negative IE subjects had positive valve 16S rRNA gene PCR/sequencing results. 16S rRNA gene-based PCR/sequencing of heart valves is a useful diagnostic tool for pathogen identification in patients with blood culture-negative IE undergoing valve surgery in routine clinical practice.

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

A case of coronavirus disease 2019-infected liver transplant donor.

Coronavirus disease 2019 (COVID-19) is a novel infectious disease that continues to spread on a global scale. There has been growing concern about donor-derived transmissions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present the case of a patient who underwent ABO-incompatible living donor liver transplantation without knowing that the liver donor was infected with COVID-19 during the donation procedure. In this case, the donor-derived transmission to the recipient was not identified, and the liver donor was found to be recovering from a COVID-19 infection. The donor-derived transmission was not identified.

Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019.

Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID-19). This study was conducted to evaluate the diagnostic performance of an immunochromatography-based assay of human serum for COVID-19. The present study enrolled 149 subjects who had been tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 and were classified into two groups: 70 who were positive for COVID-19 and 79 who were negative for COVID-19 based on RT-PCR. An immunochromatography-based COVID-19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT-PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID-19 and in three subjects (3.8%) classified as negative for COVID-19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1-97.6) and 96.2% (95% CI: 89.3-99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903-0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography-based COVID-19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID-19, especially in the presence of IgM or IgG antibodies.

Impact of health care-associated community-onset cellulitis in Korea: a multicenter study.

We conducted a multicenter study to determine the clinical and microbiological characteristics of health care-associated (HCA) cellulitis in Korea. We retrospectively reviewed the medical records of patients who had been diagnosed with community-onset cellulitis. Of the 2208 cellulitis patients, 232 (10.5%) had HCA cellulitis, 1243 (56.3%) patients were hospitalized, and 15 (0.7%) died in hospital. Compared with community-acquired (CA) cellulitis, patients with HCA cellulitis were older and more frequently presented with comorbidity and septic shock. A total of 355 microorganisms were isolated from 314 patients (14.2%). Staphylococcus aureus (134 isolates) was the most common organism, followed by Streptococcus spp. (86 isolates) and Gram-negative fermenters (58 isolates). Methicillin-resistant S. aureus (MRSA) accounted for 29.1% (39/134) of S. aureus infections. None of the Gram-negative fermenters were resistant to carbapenem. The antibiotic susceptibility pattern of isolated microorganisms was not different between HCA and CA cellulitis. In patients with HCA cellulitis, S. aureus (11.2% [26/232] vs. 5.5% [108/1976], p = 0.001), including MRSA (4.3% [10/232] vs. 1.5% [29/1976], p = 0.003) and Gram-negative fermenters (6.0% [14/232] vs. 2.3% [44/1976], p = 0.002), were more common causative organisms than in CA-cellulitis patients. Age ≥ 65 years, septic shock, and HCA infection were statistically significant factors associated with in-hospital mortality.

Mixed Infection with Plasmodium falciparum and Plasmodium ovale in a Returned Traveller: the First Case in Korea.

Mixed-species malaria infections are often unrecognized or underestimated. We hereby report the first described case of mixed infection with Plasmodium falciparum and Plasmodium ovale malaria in a returned traveller in Korea. In August 2016, a 25-year-old returned traveller from Cameroon and Democratic Republic of Congo presented with fever. He was diagnosed as P. falciparum malaria and successfully treated with artesunate. And 5 weeks after the completion of treatment, he presented with fever and diagnosed as P. ovale infection. P. ovale infection is a rare cause of malaria and often shows delayed presentation due to its dormant liver stage as hypnozoites. At re-presentation, the immunochromatographic test and microscopic examinations of our patient did not reveal P. ovale, which was only detected via polymerase chain reaction (PCR) assay. This case highlights the importance of considering malaria infection even in persons who have previously received malaria treatment. It also shows the usefulness of PCR testing for diagnosing P. ovale infections, which often present with a low level of parasitaemia.

Clinical characteristics of hospital-onset Pneumocystis pneumonia and genotypes of Pneumocystis jirovecii in a single tertiary centre in Korea.

BACKGROUND: Pneumocystis pneumonia (PCP) may develop as a clinical manifestation of nosocomial pneumonia by means of either reactivation of resident P. jirovecii or de novo infection. However, there have been no studies describing the clinical characteristics of hospital-onset PCP. METHODS: A retrospective review of medical records was performed to identify episodes of hospital-onset PCP in a tertiary care centre in Korea between May 2007 and January 2013. We investigated whether human-to-human contact during hospitalisation contributed to PCP development by molecular analysis of the genes encoding mitochondrial large ribosomal subunit (mtLSU) rRNA and dihydropteroate synthase (DHPS) and a review of hospitalisation history. RESULTS: During the study period, 129 patients (130 episodes) were diagnosed with PCP. Of these, respiratory specimens from 94 patients during 95 PCP episodes were available for analysis. Sixteen episodes (16.8%) were categorised as hospital-onset PCP. There was a trend toward a higher proportion of haematological malignancy (43.8% [7/16] vs. 20.3% [16/79]; P = 0.058) in patients with hospital-onset PCP compared to patients with community-onset PCP. mtLSU genotype 1 was the most common, occurring in 41 (43.2%) patients. There were four possible cases of nosocomial transmission. Mutation in DHPS was not observed in any PCP episode. CONCLUSIONS: PCP can be one of the causes of nosocomial pneumonia, although the mode of acquisition and transmission of P. jirovecii remains uncertain. mtLSU genotype 1 is the predominant P. jirovecii strain in Korea.

Bone and joint infection as a predictor of community-acquired methicillin-resistant Staphylococcus aureus bacteraemia: a comparative cohort study.

BACKGROUND: A new clone of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), sequence type (ST) 72-staphylococcal chromosomal cassette mec (SCCmec) type IV/IVA without the Panton-Valentine leucocidin (PVL) genes, has been the major clonal type in Korea since 2007. However, there have been no evaluations of the clinical features, risk factors and outcomes associated with CA-MRSA bacteraemia in Korea. METHODS: Adult patients with community-acquired S. aureus bacteraemia (SAB) were enrolled between 1 January 2004 and 31 September 2012. We compared the clinical features and outcomes of CA-MRSA bacteraemia with those of community-acquired methicillin-susceptible S. aureus (CA-MSSA) bacteraemia and evaluated the risk factors for CA-MRSA infection. A microbiological study of the CA-MRSA isolates was also conducted. RESULTS: In total, 169 patients were included, i.e. 31 (18%) patients with CA-MRSA bacteraemia and 138 (82%) patients with CA-MSSA bacteraemia. Bone and joint infection [45.2% (14/31) versus 22.5% (31/138); adjusted OR, 2.61; 95% CI, 1.09-6.21] was an independent predictor of CA-MRSA bacteraemia. There were no significant differences in relapse of bacteraemia and mortality within 12 weeks after SAB between the two groups. ST72-SCCmec type IV/IVA without the PVL genes was the most common genotype, especially among bone and joint infections (64%, 9/14) as well as among the CA-MRSA isolates (71%, 22/31). CONCLUSIONS: CA-MRSA accounted for 18% of community-acquired SAB and was significantly associated with bone and joint infection. Our study suggests that CA-MRSA should be considered in patients with bone and joint infection and that empirical therapy against MRSA should be included.

Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections.

Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis.

Is caspofungin really an effective treatment for Pneumocystis jirovecii pneumonia in immunocompromised patients without human immunodeficiency virus infection? Experiences at a single center and a literature review.

Caspofungin, an antifungal agent that acts on the cell wall by inhibiting ß-1,3-glucan synthesis, is likely to be effective for treating Pneumocystis pneumonia, because one of the identifying characteristics of Pneumocystis jirovecii is the presence of ß-1,3-glucan in its cell wall. Previous case reports in which the efficacy of caspofungin was found to be favourable have supported this hypothesis. However, of 4 HIV-negative patients who received caspofungin as a salvage regimen at Asan Medical Center, none showed a response. Our negative experience opposes the optimistic view of caspofungin use for Pneumocystis pneumonia expressed in previous reports.

Epidemiology and Mortality Analysis Related to Carbapenem-Resistant Enterobacterales in Patients After Admission to Intensive Care Units: An Observational Study.

Purpose: The prevalence of carbapenem-resistant Enterobacterales (CRE) is rapidly increasing worldwide. Patients in the intensive care unit (ICU) are susceptible to CRE infections, and the related mortality rate is increased. It is necessary to understand CRE strains and risk factors for CRE infection in the ICU, to facilitate development of effective prophylactic strategies and treatments for ICU patients. Patients and Methods: This observational study was conducted in a tertiary hospital between 2016 and 2021. The subjects were patients with CRE cultured from specimens obtained after ICU admission. Genotypes of strains of CRE and carbapenemase-producing Enterobacterales (CPE) were identified, CRE infection was distinguished from mere colonization, and the clinical course of these patients was investigated. Results: Among 327 CRE cases, 84 (25.7%) showed infection and 243 (74.3%) showed colonization. Of these patients, 138 (42.2%) died. The CRE strains were Klebsiella pneumoniae (253 cases, 77.4%), Enterobacter cloacae (44 cases, 13.5%), and Escherichia coli (15 cases, 4.6%). Among CRE cases, CPE was found in 249 (76.1%), including Klebsiella pneumoniae carbapenemase (KPC) in 164 (65.9%), and Guiana extended-spectrum (GES) in 64 (25.7%). A bedridden state, longer ICU stay, chronic kidney disease, malignancy, connective tissue disease, ICU admission for cardiac arrest, and CRE infection were associated with higher mortality, but cerebrovascular disease and ICU admission for trauma were associated with lower mortality. GES outbreak was caused by person-to-person transmission and was controlled through active surveillance. Conclusion: The frequency of K. pneumoniae and KPC was the highest, but E. cloacae and GES was characteristically high in this study. Active CRE surveillance can be helpful for controlling outbreak.

Impact of a Psychiatric Consultation Program on COVID-19 Patients: An Experimental Study.

OBJECTIVE: Following the coronavirus disease-2019 (COVID-19) outbreak, the importance of addressing acute stress induced by psychological burdens of diseases became apparent. This study attempted to evaluate the effectiveness of a new mode of psychiatric intervention designed to target similar psychological crises. METHODS: Participants included 32 out of 114 COVID inpatients at a hospital in Daegu, Korea, who were assessed between March 30 and April 7, 2020. Multiple scales for screening psychological difficulties such as depressed mood, anxiety, insomnia, acute stress, and suicidality were done. Psychological problem evaluations and interventions were conducted in the form of consultations to alleviate participants' psychological challenges via telepsychiatry. The interventions' effects, as well as clinical improvements before and after the intervention, were analyzed. RESULTS: As a result of screening, 21 patients were experiencing psychological difficulties beyond clinical thresholds after COVID-19 infection (screening positive group). The remaining 11 were screening negative groups. The two groups differed significantly in past psychiatric histories (p=0.034), with the former having a higher number of diagnoses. The effect of the intervention was analyzed, and clinical improvement before and after the intervention was observed. Our intervention was found to be effective in reducing the overall emotional difficulties. CONCLUSION: This study highlighted the usefulness of new interventions required in the context of healthcare following the COVID-19 pandemic.

No recurrence of Pneumocystis jirovecii Pneumonia after solid organ transplantation regardless of secondary prophylaxis.

There are no data on the efficacy of secondary prophylaxis against Pneumocystis pneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence of Pneumocystis pneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis pneumonia during the follow-up, regardless of secondary prophylaxis.

Healthcare Workforce Response to The Coronavirus Disease Outbreak in Daegu, Korea: A Multi-Center, Cross-Sectional Survey.

BACKGROUND: Securing an available healthcare workforce is critical to respond to coronavirus disease 2019 (COVID-19); however, research investigating Korea's COVID-19 staffing response is rare. To present the fundamental data of healthcare staff in response to the surge in COVID-19 cases, we investigated the healthcare workforce response in Daegu, South Korea, which experienced the first largest outbreak of COVID-19 outside of China. MATERIALS AND METHODS: In response to the COVID-19 outbreak, this retrospective cross-sectional study analyzed data on the scale and characteristics of healthcare workers (HCWs). Additionally, it analyzed the clinical and epidemiological characteristics of HCWs infected with COVID-19 in six major teaching hospitals (five tertiary and one secondary) in Daegu from January 19 to April 30, 2020. RESULTS: During this study period, only 1.3% (n = 611) of the total hospitalized patients (n = 48,807) were COVID-19 inpatients, but they occupied 6.0% (n = 303) of the total hospital beds (n = 5,056), and 23.7% (n = 3,471) of all HCWs (n = 14,651) worked in response to COVID-19. HCWs participating in COVID-19-related works comprised 50.6% (n = 1,203) of doctors (n = 2,379), 26.3% (n = 1,571) of nurses (n = 5,982), and 11.4% (n = 697) of other HCWs (n = 6,108). Only 0.3% (n = 51) of HCWs (n = 14,651) developed COVID-19 infections from community-acquired (66.7%) or hospital-acquired (29.4%). Nurses were affected predominantly (33.3%), followed by doctors (9.8%), caregivers (7.8%), radiographers (5.9%), and others (45.1%), including nurse aides and administrative, facility maintenance, telephone appointment centers, and convenience store staff. All HCWs infected with COVID-19 recovered completely. The 32.7% (n = 333) of individuals (n = 1,018) exposed to HCWs who had COVID-19 were quarantined, and only one case of secondary transmission among them occurred. CONCLUSION: The COVID-19 pandemic has necessitated significant staffing and facility usage, which is disproportionate to the relatively low number of COVID-19 inpatients, imposing a substantial burden on healthcare resources. Therefore, beyond the current reimbursement level of the Korean National Health Insurance, a new type of rewarding system is needed to prepare hospitals for the emerging outbreaks of infectious diseases. Keeping HCWs safe from COVID-19 is crucial for maintaining the healthcare workforce during a sudden massive outbreak. Further studies are needed to determine the standards of required HCWs through detailed research on the working hours and intensity of HCWs responding to COVID-19.

Melittin Ameliorates Endotoxin-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Cell Death in Mice.

Sepsis-related acute kidney injury (AKI) is a worldwide health problem, and its pathogenesis involves multiple pathways. Lipopolysaccharide (LPS) is an endotoxin that induces systemic inflammatory responses. Melittin, a main constituent of bee venom, exerts several biological activities such as antioxidant, anti-inflammatory, and antiapoptotic actions. However, whether melittin protects against endotoxin-induced AKI remains undetermined. Here, we aimed to examine the potential action of melittin on LPS-induced renal injury and explore the mechanisms. We showed that acute renal failure and structural damage after injection of LPS were markedly attenuated by administration of melittin. The peptide also suppressed expression of markers of direct tubular damage in kidneys of the LPS-treated mice. Mechanistically, melittin reduced systemic and renal levels of cytokines and inhibited renal accumulation of immune cells with concomitant suppression of nuclear factor kappa-B pathway. Increased amounts of lipid peroxidation products after LPS treatment were largely decreased by melittin. Additionally, the peptide decreased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and enhanced nuclear factor erythroid-2-related factor 2-mediated antioxidant defenses. Moreover, melittin inhibited apoptotic and necroptotic cell death after LPS treatment. Lastly, we showed that melittin improved the survival rate of LPS-injected mice. These results suggest that melittin ameliorates endotoxin-induced AKI and mortality through inhibiting inflammation, oxidative injury, and apoptotic and necroptotic death of tubular epithelial cells.

The Association between Mortality and the Oxygen Saturation and Fraction of Inhaled Oxygen in Patients Requiring Oxygen Therapy due to COVID-19-Associated Pneumonia.

BACKGROUND: The coronavirus disease (COVID-19) can manifest in a range of symptoms, including both asymptomatic systems which appear nearly non-existent to the patient, all the way to the development of acute respiratory distress syndrome (ARDS). Specifically, COVID-19-associated pneumonia develops into ARDS due to the rapid progression of hypoxia, and although arterial blood gas analysis can assist in halting this deterioration, the current environment provided by the COVID-19 pandemic, which has led to an overall lack of medical resources or equipment, has made it difficult to administer such tests in a widespread manner. As a result, this study was conducted in order to determine whether the levels of oxygen saturation (SpO2) and the fraction of inhaled oxygen (FiO2) (SF ratio) can also serve as predictors of ARDS and the patient's risk of mortality. METHODS: This was a retrospective cohort study conducted from February 2020 to Mary 2020, with the study's subjects consisting of COVID-19 pneumonia patients who had reached a state of deterioration that required the use of oxygen therapy. Of the 100 COVID-19 pneumonia cases, we compared 59 pneumonia patients who required oxygen therapy, divided into ARDS and non-ARDS pneumonia patients who required oxygen, and then investigated the different factors which affected their mortality. RESULTS: At the time of admission, the ratios of SpO2, FiO2, and SF for the ARDS group differed significantly from those of the non-ARDS pneumonia support group who required oxygen (p<0.001). With respect to the predicting of the occurrence of ARDS, the SF ratio on admission and the SF ratio at exacerbation had an area under the curve which measured to be around 85.7% and 88.8% (p<0.001). Multivariate Cox regression analysis identified that the SF ratio at exacerbation (hazard ratio [HR], 0.916; 95% confidence interval [CI], 0.846-0.991; p=0.029) and National Early Warning Score (NEWS) (HR, 1.277; 95% CI, 1.010-1.615; p=0.041) were significant predictors of mortality. CONCLUSION: The SF ratio on admission and the SF ratio at exacerbation were strong predictors of the occurrence of ARDS, and the SF ratio at exacerbation and NEWS held a significant effect on mortality.

Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019.

BACKGROUND/AIMS: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. METHODS: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. RESULTS: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. CONCLUSION: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.