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Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.
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Background@#The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. @*Methods@#In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. @*Results@#Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300):6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or inhospital mortality rates in the study cohort before or after the propensity score-matching. @*Conclusion@#In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.
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BackgroundCoronavirus 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 is available on their efficacy in patients under active anti-cancer therapies. Materials and MethodsIn 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 in early breast cancer patients with concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. ResultsStandard 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. ConclusionOur study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations. Implications for PracticeIn this article, we present rare data on the homogeneous population of patients with early breast cancer under active anti-cancer treatments. The patients showed adequate serologic responses against SARS-CoV-2 virus after standard doses of vaccination without serious adverse events in concurrence with active adjuvant anti-cancer therapy. The patients receiving concurrent cytotoxic chemotherapy, however, have significantly lower serum anti-spike antibody titers than those under non-cytotoxic anti-cancer treatments or without treatments. Selection of the COVID-19 vaccines should be based on personalized risk stratification considering the use of concurrent cytotoxic chemotherapy and the patients medical circumstances. Booster doses of vaccination could be considered for the vulnerable population, such as elderly with comorbidities and the single standard dose of vaccination.
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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.
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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.
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Identifying additional risk factors for COVID-19 severity in numerous previously healthy patients without canonical clinical risk factors remains challenging. In this study, we investigate whether clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes various inflammatory responses, may exert COVID-19 severity. We examine the clinical impact of CHIP in 143 laboratory-confirmed COVID-19 patients. Both stratified analyses and logistic regression including the interaction between canonical risk factors and CHIP show that CHIP is an independent risk factor for severe COVID-19, especially in previously healthy patients. Analyses of 60,310 single-cell immune transcriptome profiles identify distinct immunological signatures for CHIP (+) severe COVID-19 patients, particularly in classical monocytes, with a marked increase in pro-inflammatory cytokine responses and potent IFN-{gamma} mediated hyperinflammation signature. We further demonstrate that the enhanced expression of CHIP (+) specific IFN-{gamma} response genes is attributed to the CHIP mutation-dependent epigenetic reprogramming of poised or bivalent cis-regulatory elements. Our results highlight a unique immunopathogenic mechanism of CHIP in the progression of severe COVID-19, which could be extended to elucidate how CHIP contributes to a variety of human infectious diseases.
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Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-{lambda}1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1. We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.
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Background@#Co-infection with bacteria and severe acute respiratory syndrome coronavirus 2 may result in greater use of healthcare resources and a poor prognosis. Therefore, early selection and use of optimal antibiotics are essential. The direct rapid antibiotic susceptibility test (dRAST) can detect antibiotic resistance within 6 h of a Gram smear result. This study aimed to assess the effectiveness of dRAST for improving early selection of appropriate antibiotics for coronavirus disease 2019 (COVID-19) patients with bacteremia. @*Materials and Methods@#This retrospective study included 96 blood culture-positive COVID-19 patients. Bacterial isolates and antimicrobial resistance profiles of each case were evaluated. Cases were divided into two groups based on whether they underwent conventional antibiotic susceptibility test (AST) or dRAST. The time to optimal targeted treatment for the two groups was investigated and compared. In addition, we examined the proportion of cases for which appropriate antibiotics were selected and broad spectrum antibiotics were administered at 72 h from blood sample collection. @*Results@#The mean time to optimal targeted antibiotic treatment was shorter for the dRAST group [55.7; standard deviation (SD), 28.7 vs. 92.3; SD, 51.1 h; P = 0.041]. The proportion of cases receiving optimal targeted antibiotics 72 h after blood collection for culture was higher [6/10 (60.0%) vs. 10/25 (40.0%)] and the percentage receiving broad spectrum antibiotics at 72 h was lower [6/10 (60.0%) vs. 19/25 (76.0%)] in the dRAST group than in the conventional AST group. In terms of microbiology profile, the contamination rate was high (35.5%) and multidrug-resistant strains were common (63.2%) in COVID-19 patients with bacteremia. @*Conclusion@#Application of dRAST for selection of antibiotics to treat bacteremia in COVID-19 patients may enable earlier and optimal treatment. The high incidence of contamination and resistant organisms in blood cultures from COVID-19 patients suggest that dRAST may speed up appropriate targeted treatment.
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We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test.We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8–32.0%) and 100% (95% CI, 95.3–100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7–46.1%), and 41.1% (95% CI, 21.6–64.0%), respectively.
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Applying work restrictions for asymptomatic healthcare personnel (HCP) with potential exposure to coronavirus disease 2019 (COVID-19) is recommended to prevent transmission from potentially contagious HCP to patients and other HCP. However, it can lead to understaffing, which threatens the safety of both patients and HCP. We evaluated 203 COVID-19 exposure events at a single tertiary hospital from January 2020 to June 2021. A total of 2,365 HCP were potentially exposed, and work restrictions were imposed on 320 HCP, leading to the loss of 3,311 working days. However, only one of the work-restricted HCP was confirmed with COVID-19. During the study period, the work restriction measures might be taken excessively compared to their benefit, so establishing more effective standards for work restriction is required.
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We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test.We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8–32.0%) and 100% (95% CI, 95.3–100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7–46.1%), and 41.1% (95% CI, 21.6–64.0%), respectively.
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Applying work restrictions for asymptomatic healthcare personnel (HCP) with potential exposure to coronavirus disease 2019 (COVID-19) is recommended to prevent transmission from potentially contagious HCP to patients and other HCP. However, it can lead to understaffing, which threatens the safety of both patients and HCP. We evaluated 203 COVID-19 exposure events at a single tertiary hospital from January 2020 to June 2021. A total of 2,365 HCP were potentially exposed, and work restrictions were imposed on 320 HCP, leading to the loss of 3,311 working days. However, only one of the work-restricted HCP was confirmed with COVID-19. During the study period, the work restriction measures might be taken excessively compared to their benefit, so establishing more effective standards for work restriction is required.
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Background@#Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols.This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP).Materials and @*Methods@#This prospective single-armed observational study was conducted in 2 ICUs of a single hospital. The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated. @*Results@#During the 7-week study period, no positive screening case was reported among a total of 142 patients. Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks. @*Conclusion@#A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable.