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.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

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.

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.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Comparable humoral and cellular immunity against Omicron variant BA.4/5 of once-boosted BA.1/2 convalescents and twice-boosted COVID-19-naïve individuals.

The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with no prior coronavirus disease-19 (COVID-19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID-19 (n = 16), boosted once and had COVID-19 when BA.1/2 was dominant in Korea (Hybrid-6M group, n = 27), and boosted twice and did not have COVID-19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo BA.4/5 , antigen-specific memory CD4+ and CD8+ T-cell responses against BA.4/5, and B-cell responses against SARS-CoV-2 wild-type did not differ statistically between the Hybrid-6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid-6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.

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.

Incidence, Severity, and Mortality of Influenza During 2010-2020 in Korea: A Nationwide Study Based on the Population-Based National Health Insurance Service Database.

BACKGROUND: The epidemiology of influenza is commonly used to understand and establish relevant health policies for emerging respiratory infections, including coronavirus disease 2019 (COVID-19). However, Korea has no confirmed nationwide data on influenza incidence, severity, and mortality rate. METHODS: We conducted a cross-sectional study to obtain epidemic data on influenza at the national level using National Health Insurance claims data during 2010 to 2020. Influenza cases were defined as 90-day timeframe episodes based on all inpatient and outpatient claims data with disease code J09, J10, and J11. Influenza incidence, severity, and mortality rate were calculated, and logistic regressions were performed to assess the associations of demographic characteristics and comorbidity with influenza-related hospitalization, severe illness, and death. RESULTS: There were 0.4-5.9% influenza cases in the population from 2010 to 2020, with 9.7-18.9%, 0.2-0.9%, and 0.03-0.08% hospitalized, used in the intensive care unit, and dead, respectively. Age-standardized incidence and mortality rates were 424.3-6847.4 and 0.2-1.9 per 100,000 population, respectively. While more than half of the influenza cases occurred in populations aged younger than 20 years, deaths in older than 60 years accounted for more than two-thirds of all deaths. CONCLUSION: This study provided the simplest but most important statistics regarding Korean influenza epidemics as a reference. These can be used to understand and manage other new acute respiratory diseases, including COVID-19, and establish influenza-related policies.

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.

Risk Factors for the Prescription of Ineffective Antiviral Candidates for COVID-19 During the Early Pandemic Period in Korea.

BACKGROUND: Although the evidence of treatment for coronavirus disease 2019 (COVID-19) changed rapidly, little is known about the patterns of potential pharmacological treatment during the early period of the COVID-19 pandemic in Korea and the risk factors for ineffective prescription. METHODS: Using claims data from the Korean National Health Insurance System, this retrospective cohort study included admission episodes for COVID-19 from February to December 2020. Ineffective antiviral prescriptions for COVID-19 were defined as lopinavir/ritonavir (LPN/r) and hydroxychloroquine (HCQ) prescribed after July 2020, according to the revised National Institute of Health COVID-19 treatment guidelines. Factors associated with ineffective prescriptions, including patient and hospital factors, were identified by multivariate logistic regression analysis. RESULTS: Of the 15,723 COVID-19 admission episodes from February to June 2020, 4,183 (26.6%) included prescriptions of LPN/r, and 3,312 (21.1%) included prescriptions of HCQ. Of the 48,843 admission episodes from July to December 2020, after the guidelines were revised, 2,258 (4.6%) and 182 (0.4%) included prescriptions of ineffective LPN/r and HCQ, respectively. Patient factors independently associated with ineffective antiviral prescription were older age (adjusted odds ratio [aOR] per 10-year increase, 1.17; 95% confidence interval [CI], 1.14-1.20) and severe condition with an oxygen requirement (aOR, 2.49; 95% CI, 2.24-2.77). The prescription of ineffective antiviral drugs was highly prevalent in primary and nursing hospitals (aOR, 40.58; 95% CI, 31.97-51.50), public sector hospitals (aOR, 15.61; 95% CI, 12.76-19.09), and regions in which these drugs were highly prescribed before July 2020 (aOR, 10.65; 95% CI, 8.26-13.74). CONCLUSION: Ineffective antiviral agents were prescribed to a substantial number of patients during the first year of the COVID-19 pandemic in Korea. Treatment with these ineffective drugs tended to be prolonged in severely ill patients and in primary and public hospitals.

Persistent Antibody Responses Up to 18 Months After Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. METHODS: Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (immunoglobulin [Ig]A, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. RESULTS: Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8- to 11-fold lower than against wild-type viruses (P<.001). CONCLUSIONS: Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. However, humoral immune activity against more recently circulating variants was reduced in this population.

Comparison of Complications after Coronavirus Disease and Seasonal Influenza, South Korea.

We conducted a retrospective cohort study using claims data to determine the number and types of complications from coronavirus disease (COVID-19) that patients experience and which patients are more vulnerable to those complications compared with complications in patients with influenza. Among the cohort, 19.6% of COVID-19 patients and 28.5% of influenza patients had >1 new complication. In most complications, COVID-19 patients had lower or similar relative risk compared with influenza patients; exceptions were hair loss, heart failure, mood disorder, and dementia. Young to middle-aged adult COVID-19 patients and patients in COVID-19 hotspots had a higher risk for complications. Overall, COVID-19 patients had fewer complications than influenza patients, but caution is necessary in high-risk groups. If the fatality rate for COVID-19 is reduced through vaccination, management strategies for this disease could be adapted, similar to those for influenza management, such as easing restrictions on economic activity or requirements for close-contact isolation.

Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. MATERIALS AND METHODS: In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. RESULTS: Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. CONCLUSION: Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.

Broad humoral and cellular immunity elicited by one-dose mRNA vaccination 18 months after SARS-CoV-2 infection.

BACKGROUND: Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. METHODS: We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. RESULTS: A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. CONCLUSION: One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

How We Have Treated Severe to Critically Ill Patients With Coronavirus Disease 2019 in Korea.

Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and the coronavirus disease 2019 (COVID-19) pandemic currently continues. In response to this unprecedented pandemic, several researchers and medical staff have struggled to find appropriate treatments for COVID-19. Patients with mild symptoms can recuperate with symptomatic care, however establishing treatment for severe to critically ill patients who can have a high mortality has been essential. Accordingly, the guidelines for COVID-19 treatment have evolved through numerous trials and errors and have been relatively well established to date. In the Republic of Korea, several evidence-based guidelines for COVID-19 treatment were released and revised, reflecting various research and regional medical conditions. To date, approximately 3 years after the beginning of the COVID-19 pandemic, we are reflecting on the changes in the guidelines thus far and have summarized the treatment experience of severe to critically ill patients with COVID-19. The Korean guidelines for COVID-19 treatment have been updated continuously as the National Institutes of Health (NIH) guidelines have changed. Dexamethasone is currently used as the backbone for the treatment of severe to critically ill patients with COVID-19, and remdesivir, baricitinib, and tocilizumab can be added depending on a patient's situation. In addition, venous thromboembolism prophylaxis is one of the important adjunctive therapies for patients with severe COVID-19. In the clinical field, treatment of severely ill patients with COVID-19 based on guidelines is widely practiced by medical staff and established currently.

Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy.

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.

Kinetics of Neutralizing Antibody Responses Against SARS-CoV-2 Delta Variant in Patients Infected at the Beginning of the Pandemic.

We investigated the kinetics of the neutralizing antibody responses to the severe acute respiratory syndrome-coronavirus-2 delta variant over the course of 1 year in 16 patients infected at the beginning of the pandemic. In patients with severe disease, neutralizing responses to the delta variant were detectable, albeit at lower levels than responses to the wild type. Neutralizing responses to the delta variant were undetectable, however, in asymptomatic persons. This finding implies that the vaccination strategy for persons with past natural infection should depend on the severity of the previous infection.