Blood culture-free ultra-rapid antimicrobial susceptibility testing.

Treatment assessment and patient outcome for sepsis depend predominantly on the timely administration of appropriate antibiotics1-3. However, the clinical protocols used to stratify and select patient-specific optimal therapy are extremely slow4. In particular, the major hurdle in performing rapid antimicrobial susceptibility testing (AST) remains in the lengthy blood culture procedure, which has long been considered unavoidable due to the limited number of pathogens present in the patient's blood. Here we describe an ultra-rapid AST method that bypasses the need for traditional blood culture, thereby demonstrating potential to reduce the turnaround time of reporting drug susceptibility profiles by more than 40-60 h compared with hospital AST workflows. Introducing a synthetic beta-2-glycoprotein I peptide, a broad range of microbial pathogens are selectively recovered from whole blood, subjected to species identification or instantly proliferated and phenotypically evaluated for various drug conditions using a low-inoculum AST chip. The platform was clinically evaluated by the enrolment of 190 hospitalized patients suspected of having infection, achieving 100% match in species identification. Among the eight positive cases, six clinical isolates were retrospectively tested for AST showing an overall categorical agreement of 94.90% with an average theoretical turnaround time of 13 ± 2.53 h starting from initial blood processing.

Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

BACKGROUND: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. OBJECTIVES: We aimed to identify independent risk factors for IE in patients with VGS BSI. METHODS: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. RESULTS: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). CONCLUSIONS: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Real-time application of ITS and D1-D3 nanopore amplicon metagenomic sequencing in fungal infections: Enhancing fungal infection diagnostics.

While fungal infections cause considerable morbidity and mortality, the performance of the current diagnostic tests for fungal infection is low. Even though fungal metagenomics or targeted next-generation sequencing have been investigated for various clinical samples, the real-time clinical utility of these methods still needs to be elucidated. In this study, we used internal transcribed spacer (ITS) and D1-D3 ribosomal DNA nanopore amplicon metagenomic sequencing to assess its utility in patients with fungal infections. Eighty-four samples from seventy-three patients were included and categorized into 'Fungal infection,' 'Fungal colonization,' and 'Fungal contamination' groups based on the judgement of infectious disease specialists. In the 'Fungal infection' group, forty-seven initial samples were obtained from forty-seven patients. Three fungal cases detected not by the sequencing but by conventional fungal assays were excluded from the analysis. In the remaining cases, the conventional fungal assay-negative/sequencing-positive group (n=11) and conventional fungal assay-positive/sequencing-positive group (n=33) were compared. Non-Candida and non-Aspergillus fungi infections were more frequent in the conventional-negative/sequencing-positive group (p-value = 0.031). We demonstrated the presence of rare human pathogens, such as Trichosporon asahii and Phycomyces blakesleeanus. In the 'Fungal infection' group and 'Fungal colonization' group, sequencing was faster than culturing (mean difference = 4.92 days, p-value < 0.001/ mean difference = 4.67, p-value <0.001). Compared to the conventional diagnostic methods including culture, nanopore amplicon sequencing showed a shorter turnaround time and a higher detection rate for uncommon fungal pathogens.

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.

Delay in the diagnosis of Brucella abortus bacteremia in a nonendemic country: a case report.

BACKGROUND: It is challenging to diagnose brucellosis in nonendemic regions because it is a nonspecific febrile disease. The accurate identification of Brucella spp. in clinical microbiology laboratories (CMLs) continues to pose difficulties. Most reports of misidentification are for B. melitensis, and we report a rare case of misidentified B. abortus. CASE PRESENTATION: A 67-year-old man visited an outpatient clinic complaining of fatigue, fever, and weight loss. The patient had a history of slaughtering cows with brucellosis one year prior, and his Brucella antibody tests were negative twice. After blood culture, the administration of doxycycline and rifampin was initiated. The patient was hospitalized due to a positive blood culture. Gram-negative coccobacilli were detected in aerobic blood culture bottles, but the CML's lack of experience with Brucella prevented appropriate further testing. Inaccurate identification results were obtained for a GN ID card of VITEK 2 (bioMérieux, USA) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using a MALDI Biotyper (Bruker, Germany). The strain showed 100.0% identity with Brucella spp. according to 16S rRNA sequencing. MALDI-TOF MS peaks were reanalyzed using the CDC MicrobeNet database to determine Brucella spp. (score value: 2.023). The patient was discharged after nine days of hospitalization and improved after maintaining only doxycycline for six weeks. The isolate was also identified as Brucella abortus by genomic evidence. CONCLUSION: Automated identification instruments and MALDI-TOF MS are widely used to identify bacteria in CMLs, but there are limitations in accurately identifying Brucella spp. It is important for CMLs to be aware of the possibility of brucellosis through communication with clinicians. Performing an analysis with an additional well-curated MALDI-TOF MS database such as Bruker security-relevant (SR) database or CDC MicrobeNet database is helpful for quickly identifying the genus Brucella.

Anti-SARS-CoV-2 nucleocapsid antibody positivity 3 years after COVID-19.

The accurate identification of individuals without prior infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal for seroepidemiological research and vaccine trials. Because of widespread COVID-19 vaccination, the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than 3 years ago. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivities ranged from 45.5% to 87.9% depending upon the immunoassay used. The study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in participants with a distant COVID-19 history in seroepidemiological or vaccine research.

An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation.

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

Clinical outcomes and immunological features of COVID-19 patients receiving B-cell depletion therapy during the Omicron era.

Background: The clinical outcomes and immunological features of coronavirus disease 2019 (COVID-19) patients receiving B-cell depletion therapy (BCDT), especially in Omicron variant era, have not been fully elucidated. We aimed to investigate the outcomes and immune responses of COVID-19 patients receiving BCDT during the Omicron period.Methods: We retrospectively compared clinical outcomes between COVID-19 patients treated with BCDT (the BCDT group) and those with the same underlying diseases not treated with BCDT (the non-BCDT group). For immunological analyses, we prospectively enrolled COVID-19 patients receiving BCDT and immunocompetent COVID-19 patients as controls. We measured humoral and cellular immune responses using the enzyme-linked immunosorbent assay and flow cytometry.Results: Severe to critical COVID-19 was more frequent in the BCDT group than in the non-BCDT group (41.9% vs. 28.3%, p = .030). BCDT was an independent risk factor for severe to critical COVID-19 (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21-4.04, p = .010) as well as for COVID-19-related mortality (aOR 4.03, 95% CI 1.17-13.86, p = .027). Immunological analyses revealed that patients receiving BCDT had lower anti-S1 IgG titres and a tendency to higher proportions of activated CD4+ T-cells than the controls.Conclusions: BCDT was associated with worse COVID-19 outcomes in the Omicron period. Humoral immune response impairment and T-cell hyperactivation were the main immunological features of COVID-19 patients treated with BCDT, which may have contributed to the worse outcomes of COVID-19 in this population.

Impact of T-Cell Engagers on COVID-19-Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy.

PURPOSE: B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19-related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy. MATERIALS AND METHODS: This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis. Multivariable logistic regression was used to identify factors associated with severe to critical COVID-19 and COVID-19-related mortality. RESULTS: Of 54 patients with B-cell lymphomas and COVID-19 who received B-cell depleting therapy, 14 were treated with TCE (TCE group) and 40 with rituximab (RTX group). COVID-19-related mortality was higher in the TCE group than in the RTX group (57.1% vs. 12.5%, p=0.002). In multivariable analyses, TCE therapy (adjusted odds ratio [aOR], 7.08; 95% confidence interval [CI], 1.29 to 38.76; p=0.024) and older age (aOR, 1.06; 95% CI, 1.00 to 1.13; p=0.035) were associated with severe to critical COVID-19. TCE therapy (aOR, 8.98; 95% CI, 1.48 to 54.40; p=0.017), older age (aOR, 1.13; 95% CI, 1.02 to 1.26; p=0.022), and prior bendamustine therapy (aOR, 7.78; 95% CI, 1.17 to 51.65; p=0.034) were independent risk factors for COVID-19-related mortality. CONCLUSION: B-cell lymphoma patients treated with TCE had significantly worse outcomes from COVID-19 than those treated with RTX. TCE therapy should be used with caution in B-cell lymphoma patients during the COVID-19 epidemic.

Significant Reduction in External Ventricular Drain-Related Infections After Introducing a Novel Bundle Protocol: A Before and After Trial.

BACKGROUND: External ventricular drain (EVD)-related infection (ERI) is a serious complication in neurosurgical patients. The estimated ERI rates range from 5 to 20 cases per 1,000 EVD catheter days. The pathophysiology of ERI is similar to central line-associated bloodstream infections (CLABSIs) stemming from skin-derived bacterial colonization. The use of bundle management can reduce CLABSI rates. Due to the pathogenic similarities between infections related to the two devices, we developed and evaluated the effectiveness of an ERI-bundle protocol based on CLABSI bundles. METHODS: From November 2016 to November 2021, we conducted a study to evaluate the effectiveness of an ERI-bundle protocol. This study adopted a before-and-after trial, comparing the ERI rates for the 2 years before and 3 years after the introduction of the newly developed ERI-bundle protocol. We also analyzed the contributing factors to ERI using logistic regression analysis. RESULTS: A total of 183 patients with 2,381 days of catheter use were analyzed. The ERI rate decreased significantly after the ERI-bundle protocol from 16.7% (14 of 84; 14.35 per 1,000 catheter days) to 4.0% (4 of 99; 3.21 per 1,000 catheter days) (P = 0.004). CONCLUSION: Introduction of the ERI-bundle protocol was very effective in reducing ERI.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

Adverse Drug Events Associated With Remdesivir in Real-World Hospitalized Patients With COVID-19, Including Vulnerable Populations: A Retrospective Multicenter Study.

BACKGROUND: Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women. METHODS: This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women. RESULTS: Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085). CONCLUSION: A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

Possibility of Decreasing Incidence of Human Immunodeficiency Virus Infection in Korea.

BACKGROUND: The number of newly diagnosed cases of human immunodeficiency virus (HIV) infection in Korea, which had increased until 2019, has markedly decreased since the coronavirus disease 2019 pandemic started. This study evaluated whether the decrease is due to a reduction in the incidence of HIV infection and/or delayed diagnosis during the pandemic. MATERIALS AND METHODS: We reviewed the medical records of 587 newly diagnosed patients with HIV infection between February 2018 and January 2022 from four general hospitals, and their characteristics were compared between the pre-pandemic and pandemic periods. The lapse time from infection to diagnosis was estimated using an HIV modeling tool. RESULTS: The estimated mean times to diagnosis were 5.68 years (95% confidence interval [CI]: 4.45 - 6.51 years) and 5.41 years (95% CI: 4.09 - 7.03 years) before and during the pandemic, respectively (P = 0.016). The proportion of patients with acquired immunodeficiency syndrome-defining illnesses, expected to visit hospitals regardless of the pandemic, decreased from 17.2% before the pandemic to 11.9% during the pandemic (P = 0.086). CONCLUSION: The decrease in the number of newly diagnosed cases of HIV infection in Korea might have resulted from an actual decrease in the incidence of HIV infection rather than a worsening of underdiagnosis or delayed diagnosis.

Empirical vs pre-emptive broad-spectrum antifungal therapy for acute myelogenous leukaemia in the era of antimould prophylaxis.

INTRODUCTION: This study compared clinical outcomes in patients with acute myelogenous leukaemia (AML) who developed prolonged (≥4 days) febrile neutropenia (FN) and received either empirical or pre-emptive antimould prophylaxis in order to evaluate the need for routine empirical antifungal therapy. METHODS: This retrospective study reviewed adult patients (aged ≥18 years) with AML who developed prolonged FN and received antimould prophylaxis during induction or re-induction chemotherapy at a single centre between September 2016 and December 2020. Patients were categorized into pre-emptive or empirical groups based on whether or not there was clinical evidence of invasive fungal infection (IFI) at the start of antifungal treatment, respectively. Clinical outcomes were compared between the two groups after propensity score matching (PSM). RESULTS: In total, 229 chemotherapy episodes (36 and 193 in the empirical and pre-emptive groups, respectively) were analysed. In the pre-emptive group, broad-spectrum antifungal therapy was administered in 45 (23.3%) episodes. After 1:3 PSM, there were no significant differences between the empirical and pre-emptive groups in terms of the incidence of proven or probable IFI [0/36 (0%) vs 5/97 (5.2%); P=0.323], all-cause mortality [3/36 (8.3%) vs 4/97 (4.1%); P=0.388] and IFI-related mortality [0/36 (0.0%) vs 1/45 (2.2%); P=0.556]. CONCLUSION: The differences in clinical outcomes between empirical and pre-emptive antifungal therapy in patients with AML who received antimould prophylaxis were not significant. Therefore, broad-spectrum antifungal therapy in patients receiving antimould prophylaxis may be delayed until there is clear evidence of IFI.

Effect of Wearing Personal Protective Equipment (PPE) for COVID-19 Treatment on Blood Culture Contamination: Implication for Optimal PPE Strategies.

The personal protective equipment (PPE) used to minimize exposure to hazards can hinder healthcare workers from performing sophisticated procedures. We retrospectively reviewed 77,535 blood cultures (202,012 pairs) performed in 28,502 patients from January 2020 to April 2022. The contamination rate of all blood cultures was significantly elevated in the coronavirus disease 2019 ward at 4.68%, compared to intensive care units at 2.56%, emergency rooms at 1.13%, hematology wards at 1.08%, and general wards at 1.07% (All of P < 0.001). This finding implies that wearing PPE might interfere with adherence to the aseptic technique. Therefore, a new PPE policy is needed that considers the balance between protecting healthcare workers and medical practices.

Impact of Enhanced in-Hospital Infection Prevention During the COVID-19 Pandemic on Postoperative Pneumonia in Older Surgical Patients.

Purpose: We aimed to investigate the impact of enhanced in-hospital infection prevention during the coronavirus disease 2019 (COVID-19) pandemic on postoperative pneumonia in older surgical patients. Patients and Methods: We retrospectively reviewed the electronic medical records of consecutive patients ≥70 years who underwent elective surgery between 2017 and 2021 at our institution. All perioperative variables were retrieved from the electronic medical records. The primary outcome was new-onset postoperative pneumonia during the hospitalization period. Since February 2020, our institution implemented a series of policies to enhance infection prevention, hence patients were divided into groups according to whether they underwent surgery before or during the COVID-19 pandemic. An interrupted time series analysis was performed to evaluate the difference between pre- and post-intervention slopes of the primary outcome. Results: Among the 29,387 patients included in the study, 10,547 patients underwent surgery during the COVID-19 pandemic. Although there was a decreasing trend of the monthly incidence rate of postoperative pneumonia compared to before the COVID-19 pandemic, there was no statistical significance in the trend (slope before COVID-19 period: ß-coefficient, -0.007; 95% CI, -0.022 to 0.007). Conclusion: Our study revealed that enhanced in-hospital infection prevention implemented to manage the COVID-19 pandemic did not significantly affect the decreasing trend of postoperative pneumonia at our institution.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19.

Introduction: Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response. Methods: We prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively. Results: A total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group. Conclusion: There were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.