Real-World Effectiveness of Nirmatrelvir-Ritonavir and Its Acceptability in High-Risk COVID-19 Patients.

BACKGROUND: Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea. METHODS: To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated. RESULTS: The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07; 95% confidence interval [CI], 0.01-0.31; P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03; 95% CI, 1.00-1.07), National Early Warning Score-2 at admission (aHR, 1.36; 95% CI, 1.08-1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37; 95% CI, 0.15-0.88), and time from symptom onset to admission (aHR, 0.67; 95% CI, 0.48-0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%). CONCLUSION: Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication.

Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding.

BACKGROUND: Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated. METHODS: Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days. RESULTS: A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively. CONCLUSIONS: Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.

Interspecies differences in clinical characteristics and risk factors for third-generation cephalosporin resistance between Escherichia coli and Klebsiella pneumoniae bloodstream infection in patients with liver cirrhosis.

This retrospective study aimed to clarify the interspecies differences in the clinical characteristics and risk factors of bloodstream infection (BSI) due to third-generation cephalosporin-resistant (3GC-R) Escherichia coli (EC) and Klebsiella pneumoniae (KP) in patients with liver cirrhosis (LC). KP BSI had more comorbidities and higher treatment failure rate than EC BSI. Non-alcoholic LC was a risk factor for treatment failure in EC, whereas it was not associated with KP. Risk factors for BSI due to 3GC-R strain were nosocomial infection in EC, and ß-lactam/fluoroquinolone treatment ≤ 30 days in KP. These results could help predict outcomes of BSI and improve clinical practice.

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.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Clinical outcomes of mild to moderate coronavirus disease 2019 patients treated with Regdanvimab in delta-variant outbreak: Retrospective cohort study.

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation.

Performance of STANDARD™ M10 SARS-CoV-2 Assay for the Diagnosis of COVID-19 from a Nasopharyngeal Swab.

The STANDARD™ M10 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) assay (M10 assay) (SD Biosensor Inc., Suwon, Korea) is a rapid, fully-automated, cartridge-type molecular diagnostic assay that detects SARS-CoV-2 RNA using primers and probes for each target gene (ORF1ab gene, E gene). This study evaluated its performance by assessing its concordance with the approved SARS-CoV-2 real-time PCR assay. Tests were performed on 80 nasopharyngeal samples. The sensitivity and specificity of the M10 assay were 100%. The M10 assay effectively diagnosed SARS-CoV-2 infection, and it was comparable to the approved SARS-CoV-2 real-time PCR assay. It is a viable point-of-care test due to its short turnaround time.

Prevalence of and factors associated with inappropriate Clostridioides difficile testing in a teaching hospital in Korea.

BACKGROUND: Given the increasing incidence of Clostridioides difficile infections in Korea, there has been an increase in inappropriate testing for C. difficile, which has rendered overdiagnosis of asymptomatic colonisers common. We aimed to investigate the appropriateness of C. difficile testing and the related factors. METHODS: We retrospectively reviewed the medical records of patients who were admitted to a 1300-bed tertiary-care teaching hospital in Korea and were tested for C. difficile infection from September 2019 to November 2019. We performed logistic regression analysis to investigate factors related to inappropriate testing. Further, a survey was conducted on physicians to assess the knowledge and ordering patterns of C. difficile testing. RESULTS: We included 715 tests from 520 patients in the analysis. Testing was classified as hospital-onset and community-onset and subclassified as appropriate and inappropriate following an algorithmic method. Among the 715 tests, 576 (80.6%) and 139 (19.6%) tests were classified as hospital-onset and community-onset, respectively. Among the hospital-onset tests, 297 (52%) were considered inappropriate. The risk of inappropriate testing increased when C. difficile tests were conducted in the emergency room (OR 24.96; 95% CI 3.12-199.98) but decreased in intensive care units (OR 0.36, 95% CI 0.19-0.67). The survey was conducted on 61 physicians. Internal medicine physicians had significantly higher scores than non-internal medicine physicians (7.1 vs. 5.7, p = 0.001). The most frequently ordered combination of tests was toxin + glutamate dehydrogenase (47.5%), which was consistent with the ordered tests. CONCLUSION: Almost half of the C. difficile tests were performed inappropriately. The patient being located in the emergency room and intensive care unit increased and decreased the risk of inappropriate testing, respectively. In a questionnaire survey, we showed that internal medicine physicians were more knowledgeable about C. difficile testing than non-internal medicine physicians. There is a need to implement the diagnostic stewardship for C. difficile, especially through educational interventions for emergency room and non-internal medicine physicians.

Are coveralls required as personal protective equipment during the management of COVID-19 patients?

OBJECTIVES: Few studies have investigated the contamination of personal protective equipment (PPE) during the management of patients with severe-to-critical coronavirus disease (COVID-19). This study aimed to determine the necessity of coveralls and foot covers for body protection during the management of COVID-19 patients. METHODS: PPE samples were collected from the coveralls of physicians exiting a room after the management of a patient with severe-to-critical COVID-19 within 14 days after the patient's symptom onset. The surface of coveralls was categorized into coverall-only parts (frontal surface of the head, anterior neck, dorsal surface of the foot cover, and back and hip) and gown-covered parts (the anterior side of the forearm and the abdomen). Sampling of the high-contact surfaces in the patient's environment was performed. We attempted to identify significant differences in contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between the coverall-only and gown-covered parts. RESULTS: A total of 105 swabs from PPEs and 28 swabs from patient rooms were collected. Of the PPE swabs, only three (2.8%) swabs from the gown-covered parts were contaminated with SARS-CoV-2. However, 23 of the 28 sites (82.1%) from patient rooms were contaminated. There was a significant difference in the contamination of PPE between the coverall-only and gown-covered parts (0.0 vs 10.0%, p = 0.022). CONCLUSIONS: Coverall contamination rarely occurred while managing severe-to-critical COVID-19 patients housed in negative pressure rooms in the early stages of the illness. Long-sleeved gowns may be used in the management of COVID-19 patients.

Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.

The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

Clinical and Laboratory Factors Associated with Symptom Development in Asymptomatic COVID-19 Patients at the Time of Diagnosis.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19.

Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARS-CoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results. The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.