Development and validation of machine learning-based models for predicting healthcare-associated bacterial/fungal infections among COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

Impact of an educational program on reducing health care-associated meningitis or ventriculitis in the neurosurgical intensive care unit.

BACKGROUND: Health care-associated meningitis or ventriculitis (HCAMV) is a serious complication in different neurosurgical procedures and is associated with significant morbidity and mortality. We aimed to investigate whether an educational intervention program could reduce the HCAMV incidence in patients undergoing postsurgery external ventricular drainage and wound management. METHODS: We enrolled 2,904 patients from the neurosurgery intensive care unit between January 1, 2016 and December 31, 2018. The medical staff undertook an educational program developed by a multidisciplinary team on correct external ventricular drainage insertion and maintenance. The program included a 9-page self-learning module on the HCAMV risk factors and operational improvements. Each participant completed a pre- and posttest on their HCAMV knowledge. RESULTS: We found that 38 of 693 (5.48%) patients presented with infection in the preintervention 9-month period. In the 27-month postintervention period, the proportion of HCAMV incidence dropped by 52.19% (P < .0001) to 58 of 2,211 (2.62%) patients. CONCLUSIONS: Educational intervention aimed at the neurosurgery intensive care unit staff could significantly reduce the HCAMV rate, leading to a significant decline in the cost, morbidity, and mortality caused by neurosurgical procedures.

Dynamic changes of lymphocyte counts in adult patients with severe pandemic H1N1 influenza A.

BACKGROUND: Lymphopenia has been observed in severe pandemic influenza A/H1N1 in developed countries. However, data from developing countries are rare and dynamic change of lymphocyte counts in severe pandemic influenza A/H1N1 is scarcely reported. This study aimed to observe change of lymphocyte counts in patients with severe pandemic influenza A/H1N1 and to investigate the correlation of lymphopenia and severe pandemic influenza A/H1N1. METHODS: We retrospectively analyzed the white blood cell counts and differentials and other clinical data in 21 hospitalized patients with severe pandemic influenza A/H1N1 confirmed by reverse-transcription PCR during 2009 and 2010. RESULTS: All patients, except two cases with bacterial co-infections, had normal or reduced white blood cell counts. Seventeen (81.0%) patients had decreased lymphocyte proportions (<20%) and counts (<0.8×109/L), with the lowest value of 1.2% and 0.1×109/L respectively. A patient with nosocomial infection of influenza A/H1N1 showed that lymphopenia occurred on the first day of illness. Lymphocyte proportions and absolute counts returned to normal or slightly higher than normal in 16 of the 17 patients within 2-3weeks after the disease onset. CONCLUSIONS: Lymphopenia along with other clinical parameters may be helpful in early differential diagnosis of severe pandemic influenza A/H1N1.

Characteristics of hepatitis B core antibody level in the natural history of chronic hepatitis B.

OBJECTIVE: We aimed to analyze serum antibody to hepatitis B core antigen (anti-HBc) level during different immunological phases in the natural history of patients with chronic hepatitis B (CHB). METHODS: Serum anti-HBc levels in the immune tolerant (IT), immune clearance (IC), low replicative (LR), and HBeAg negative hepatitis (ENH) phases from 634 treatment-naïve CHB patients were measured and compared between phases and with other serum markers. RESULTS: Median serum anti-HBc levels were different between the phases of CHB. Serum anti-HBc level was highest in the ENH phase and lowest in the IT phase. Serum anti-HBc level correlated only with ALT in the IC phase (r = 0.248, p < 0.001). The area under the receiver operating characteristic curve (AUC) of anti-HBc at a cutoff value of 9.03 S/CO for differentiation of IT and IC phases was 0.689 (sensitivity 74.03%, specificity 60.23%). The AUC for differentiation of LR and ENH phases was 0.751 (sensitivity 68.32%, specificity 70.53%) at a cutoff value of 9.74 S/CO for anti-HBc. CONCLUSIONS: Serum anti-HBc levels were significantly different across different phases of CHB and were associated with hepatitis activities.

Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection.

Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.

Characterization of clinical features and outcome for human-to-human transmitted severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease identified in 2009. SFTS is mainly transmitted by contact with ticks or animals; however, sporadic reports suggested that SFTS could be transmitted among humans. OBJECTIVES: We aimed to comprehensively characterize clinical features and disease progression of SFTS acquired by human-to-human transmission. STUDY DESIGN: A retrospective study of 90 SFTS patients was performed in a tertiary hospital of Nanjing, China, from October 2010 to October 2016. Seven cases of secondary SFTS were identified based on their epidemic timeline. Their clinical presentations, dynamic laboratory results and clinical outcome were analyzed. RESULTS: First, 20 out of 83 primary SFTS patients were deceased, leading to a case-fatality ratio of 24.1%, while all secondary patients survived, suggesting a superior clinical outcome for secondary infection. Moreover, clinical symptoms and laboratory tests in primary and secondary SFTS patients were analyzed, respectively. Secondary SFTS patients developed milder clinical manifestation in the absence of neurological disorder and multiple organ failure. Further, clinical laboratory tests revealed that secondary patients had less disturbed key laboratory parameters, compared to those in primary SFTS patients. During day 7-13 post illness onset, most of the clinical laboratory results of secondary patients went back to normal range. They also had significantly lower level of viral load than primary patients. CONCLUSIONS: Secondary SFTS acquired through human-to-human transmission leads to milder clinical representations and superior prognoses compared to primary SFTS, suggesting that the transmission route makes a difference in disease progression and clinical outcome of SFTS disease.

A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients.

Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

Downregulation of Interferon-ß and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to SFTS virus infection remain unknown. A comprehensive study was conducted on a cohort of 70 patients on clinical manifestations, viral loads, modulation of cytokines, serum interferon level, immune related gene expression in peripheral blood cells, and dynamic changes of circulating dendritic cells during the acute phase of SFTSV infection. We found that high level viremia, reduced platelets, coagulation dysfunction, multi-organ injuries, elevated IL-6 and TNF-α were closely associated with the aggravation of SFTS. In addition, we demonstrated strong correlations between disease severity and the decline of serum IFN-ß and IL-1ß level, reduction of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression in monocytes and mDCs. In general, dysfunction of innate immune response and cytokine storm are both involved in the pathogenesis of SFTS. Reduction of myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the regulation of TLR3 could probably be the mechanism.