T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Severe Thrombocytopenia Caused by Vancomycin in the Intensive Care Unit: A Case Report.

Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was likely to be associated with vancomycin. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin-related severe hematotoxicity should be considered.

Rapid and Accurate Detection of SARS Coronavirus 2 by Nanopore Amplicon Sequencing.

Objective: We aimed to evaluate the performance of nanopore amplicon sequencing detection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples. Method: We carried out a single-center, prospective cohort study in a Wuhan hospital and collected a total of 86 clinical samples, including 54 pharyngeal swabs, 31 sputum samples, and 1 fecal sample, from 86 patients with coronavirus disease 2019 (COVID-19) from Feb 20 to May 15, 2020. We performed parallel detection with nanopore-based genome amplification and sequencing (NAS) on the Oxford Nanopore Technologies (ONT) minION platform and routine reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, 27 negative control samples were detected using the two methods. The sensitivity and specificity of NAS were evaluated and compared with those of RT-qPCR. Results: The viral read number and reference genome coverage were both significantly different between the two groups of samples, and the latter was a better indicator for SARS-CoV-2 detection. Based on the reference genome coverage, NAS revealed both high sensitivity (96.5%) and specificity (100%) compared with RT-qPCR (80.2 and 96.3%, respectively), although the samples had been stored for half a year before the detection. The total time cost was less than 15 h, which was acceptable compared with that of RT-qPCR (∼2.5 h). In addition, the reference genome coverage of the viral reads was in line with the cycle threshold value of RT-qPCR, indicating that this number could also be used as an indicator of the viral load in a sample. The viral load in sputum might be related to the severity of the infection, particularly in patients within 4 weeks after onset of clinical manifestations, which could be used to evaluate the infection. Conclusion: Our results showed the high sensitivity and specificity of the NAS method for SARS-CoV-2 detection compared with RT-qPCR. The sequencing results were also used as an indicator of the viral load to display the viral dynamics during infection. This study proved the wide application prospect of nanopore sequencing detection for SARS-CoV-2 and may more knowledge about the clinical characteristics of COVID-19.

Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China.

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.

Chronic Active Hepatitis B with COVID-19 in Pregnancy: A Case Report.

Currently, infection with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during pregnancy is a problem worthy of attention, especially in patients with underlying diseases. In this case report, we present a case of chronic active hepatitis B with COVID-19 in pregnancy. A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment, was admitted to the hospital with chronic active hepatitis B, and tested positive for SARS-CoV-2 infection. In this case, we applied liver protective and antiviral agents, and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.

Identifying critically ill patients at risk of death from coronavirus disease.

BACKGROUND: A pandemic of coronavirus disease (COVID-19) has been declared by the World Health Organization (WHO) and caring for critically ill patients is expected to be at the core of battling this disease. However, little is known regarding an early detection of patients at high risk of fatality. METHODS: This retrospective cohort study recruited consecutive adult patients admitted between February 8 and February 29, 2020, to the three intensive care units (ICUs) in a designated hospital for treating COVID-19 in Wuhan. The detailed clinical information and laboratory results for each patient were obtained. The primary outcome was in-hospital mortality. Potential predictors were analyzed for possible association with outcomes, and the predictive performance of indicators was assessed from the receiver operating characteristic (ROC) curve. RESULTS: A total of 121 critically ill patients were included in the study, and 28.9% (35/121) of them died in the hospital. The non-survivors were older and more likely to develop acute organ dysfunction, and had higher Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores. Among the laboratory variables on admission, we identified 12 useful biomarkers for the prediction of in-hospital mortality, as suggested by area under the curve (AUC) above 0.80. The AUCs for three markers neutrophil-to-lymphocyte ratio (NLR), thyroid hormones free triiodothyronine (FT3), and ferritin were 0.857, 0.863, and 0.827, respectively. The combination of two easily accessed variables NLR and ferritin had comparable AUC with SOFA score for the prediction of in-hospital mortality (0.901 vs. 0.955, P=0.085). CONCLUSIONS: Acute organ dysfunction combined with older age is associated with fatal outcomes in COVID-19 patients. Circulating biomarkers could be used as powerful predictors for the in-hospital mortality.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension.

BACKGROUND: Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers (ACEIs/ARBs) had no harmful effects on coronavirus disease 2019 (COVID-19) patients complicated with hypertension. AIM: To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs. METHODS: All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study. Some patients switched from ACEIs/ARBs to calcium channel blocker (CCBs) after admission, while others continued using non-ACEIs/ARBs. We compared characteristics and clinical outcomes between these two groups of patients. RESULTS: A total of 53 patients were enrolled, 27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs. After controlling potential confounding factors using the Cox proportional hazards model, hospital stay was longer in patients who discontinued ACEIs/ARBs, with a hazard ratio of 0.424 (95% confidence interval: 0.187-0.962; P = 0.040), upon discharge than patients using other anti-hypertensive drugs. A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases [hazard ratio = 0.224 (95% confidence interval: 0.005-0.998; P = 0.0497)]. CONCLUSION: Patients in the discontinued ACEIs/ARBs group had longer hospital stays. Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

Drug-Related Problems Identified During Pharmacy Intervention and Consultation: Implementation of an Intensive Care Unit Pharmaceutical Care Model.

AIM: To identify common drug-related problems (DRPs) during pharmacy intervention and consultation in an intensive care unit (ICU); to explore the gap between physicians and pharmacists on their understanding of each other's capabilities and needs. METHOD: We conducted a single-center prospective study in the ICU of a tertiary academic hospital for 21 months. A pharmaceutical care (PC) model was implemented by a pharmacy team, and data were collected during pharmacy intervention and consultation. Data analysis was performed on identified DRPs, causes and their relationships. DRPs' frequency during intervention and consultation was compared. Problem-level descriptive analysis and network analysis were conducted using R 3.6.3. RESULT: Implementation of PC model greatly improved the efficacy of pharmacists in both interventions proposed to solve DRPs (from 13.6 to 20.1 cases per month) and number of patients being closely monitored (from 7.7 to 16.9 per month). Pharmacists identified 427 DRPs during pharmacy intervention with primarily adverse drug events (ADEs, 34.7%) and effect of treatment not optimal (25.5%), and 245 DRPs during consultation (mainly ADEs, 58.4%). About three-fifths DRPs were caused by antibiotics. Comparing DRPs identified during pharmacy intervention and consultation, physicians consulted pharmacists more on questions related to medication safety, while pharmacists also paid attention to treatment effectiveness, which was consulted less commonly. CONCLUSION: Implementation of PC model is beneficial in guiding pharmacy practice and improving efficacy especially under limited human resources. Physicians and pharmacists shall continue ensuring drug safety and be familiar with the scope of PC and clinical need for a better cooperation.

The WHO near miss criteria are appropriate for admission of critically ill pregnant women to intensive care units in China.

BACKGROUND: Evaluation of the severity of the pregnant women with suitable admission to the Intensive Care Unit (ICU) is very important for obstetricians. By now there are no criteria for critically ill obstetric patients admitted to the ICU. In this article, we investigated the admission criteria of critically ill patients admitted to the ICU in order to provide a referral basis of reasonable use of the ICU. METHODS: A retrospective analysis of critically ill pregnant women admitted to the ICU in Perking University Third Hospital in China in the last 6 years (from January 2006 to December 2011) was performed, using acute physiology and chronic health evaluation II (APACHE-II), Marshall and WHO near miss criteria to assess the severity of illness of patients. RESULTS: There were 101 critically ill pregnant patients admitted to the ICU. Among them, 25.7% women were complicated with internal or surgical diseases, and 23.8% women were patients of postpartum hemorrhage and 23.8% women were patients of pregnancy-induced hypertension. Sixty-nine cases (68.3%) were administrated with adjunct respiration with a respirator. Sixteen cases (15.8%) required 1-2 types of vasoactive drugs. Fifty-five cases (54.5%) required a hemodynamic monitoring. Seventy-three cases (72.3%) had multiple organ dysfunctions (MODS). The average duration in ICU was (7.5 ± 3.0) days. A total of 12.9%, 23.8% and 74.3% of women were diagnosed as critically ill according to the APACHE-II, Marshall and WHO near miss criteria, respectively. The rate was significantly different according to the three criteria (P < 0.01). CONCLUSIONS: The WHO near miss criteria can correctly reflect the severity of illness of pregnant women, and the WHO near miss criteria are appropriate for admission of critically ill pregnant women to ICU in China.

[Epidemiological investigation on acute respiratory distress syndrome occurring in intensive care units in Beijing from 1998 to 2003].

OBJECTIVE: To investigate incidence, causes and mortality of acute respiratory distress syndrome (ARDS) in intensive care units (ICU) in Beijing. METHODS: Patients in ICU of eight general hospitals in Beijing from May 1998 to April 2003 were retrospectively studied. ARDS was diagnosed according to the 1994 American-European consensus conference criteria. Results Of 8 482 patients admitted to ICUs in the same period, there were 383 patients (4.5%) diagnosed as having ARDS. Major primary diseases for ARDS were sepsis (21.7%), pneumonia (16.2%), surgical operation (13.1%), acute pancreatitis (12.8%) and multiple severe trauma (10.7%). The mean interval between onset of the primary disease and onset of ARDS was (61.8 +/- 43.7) hours. The overall mortality of ARDS was 52.0%, the mortality adjusted for age (< or =39, 40-64, > or =65 years old) and gender (male) showed significant changes in each year (all P<0.05), but acute physiology and chronic health evaluation II (APACHE II, < or =12, 13-19, > or =20 scores) score showed no significant changes during the 5 years. Septic shock (36.2%) and heart failure (20.6%) were major lethal causes, while only 14.6% died of respiratory failure. CONCLUSION: ARDS was frequent in ICU in Beijing, the mortality remains high, and there is no tendency to decline in recent years.

[Clinical study of relationship between serum procalcitonin and severity of multiple organ dysfunction syndrome].

OBJECTIVE: To study the correlation between serum procalcitonin (PCT) level and severity of multiple organ dysfunction syndrome (MODS). METHODS: Sixty-one patients with MODS were enrolled in this study. They were divided into infection group and non-infection group. Serum PCT were measured using an immunoluminometric assay. Acute physiology and chronic health evaluation II (APACHE II) scores and Marshall scores of the two groups were recorded and the relationship between PCT levels and APACHE II scores as well as Marshall scores was analysed. RESULTS: Serum PCT levels in patients with MODS were higher. Serum PCT [13.01(2.73, 64.79) microg/L], APACHE II [(17.50+/-5.35) scores] and Marshall score [(6.38+/-2.46) scores] of infection group were significantly higher than non-infection group [1.50 (0, 2.98) microg/L, (14.67+/-3.01) scores, and (4.62+/-2.01) scores, respectively, P<0.05 or P<0.001]. Serum PCT of infection group and non-infection group did not show correlation with APACHE II (r=0.175, P=0.281; r=0.071, P=0.759). Serum PCT of all patients with MODS showed positive correlation with Marshall score (r=0.514, P<0.001), and correlation index of infection group was higher (r=0.535, P<0.001). Serum PCT of non-infection group did not show correlation with Marshall score (r=0.003, P=0.991). CONCLUSION: Serum PCT has clinical values in judgment of the severity of infected patients complicated by MODS.