A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.

Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.94 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N = 97) and retrospectively (N = 100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay. With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.

Diabetes on sepsis outcomes in non-ICU patients: A cohort study and review of the literature.

AIMS: We sought to determine whether primary outcomes differ between non-ICU septic patients with and without type 2 diabetes (T2D). METHODS: This study utilized the Hellenic Sepsis Study Group Registry, collecting nationwide data for sepsis patients since 2006, and classified patients upon presence or absence of T2D. Patients were perfectly matched for a) Sepsis 3 definition criteria (including septic shock) b) gender, c) age, d) APACHE II score and e) Charlson's comorbidity index (CCI). Independent sample t-test and chi-square t-test was used to compare prognostic indices and primary outcomes. RESULTS: Of 4320 initially included non-ICU sepsis patients, 812 were finally analysed, following match on criteria. Baseline characteristics were age 76 [±10.3] years, 46% male, APACHE II 15.5 [±6], CCI 5.1 [±1.8], 24% infection, 63.8% sepsis and 12.2% septic shock. No significant difference was noted between two groups in qSOFA, SOFA, or suPAR1 levels (p = 0.7, 0.1 & 0.3) respectively. Primary sepsis syndrome resolved in 70.9% of cases (p = 0.9), while mortality was 24% in 28-days time. Cause of death was similar between patients with and without T2D (sepsis 17.8% vs 15.8%, heart event 3.7% vs 3.2%, CNS event 0.5% vs 0.5%, malignancy 0.7% vs 2% respectively, p = 0.6). CONCLUSIONS: DM does not appear to negatively affect outcomes in septic patients not requiring ICU.

Pulmonary nocardiosis in an immunocompetent patient with COPD: the role of defective innate response.

OBJECTIVES: Pulmonary nocardiosis is an uncommon opportunistic infection affecting mainly immunocompromised patients. We herein present a case of nocardiosis without profound underlying immunodeficiency. BACKGROUND: A female, 84-years' old patient with stage IV chronic obstructive pulmonary disease (COPD) is presented. No profound causes of immunodeficiency existed, such as HIV infection, diabetes mellitus, malignancy, alcoholism, chemotherapy or previous corticosteroid intake. The patient recovered after treatment with trimethoprim/sulfamethoxazole for 6 months. RESULTS: One year after infection resolution, stimulation of the patient's blood monocytes with Nocardia antigens revealed defective production of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-17. CONCLUSION: We provide preliminary evidence for a link between defective innate immune responses and predisposition for Nocardia infections. Further studies must be conducted in order to fully investigate this mechanism of infection acquisition.

An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients.

PURPOSE: We sought to perform a systematic review and meta-analysis of procalcitonin(PCT)-guided antibiotic therapy algorithms for critically ill adult patients. METHODS: We performed a search in PubMed and in the Cochrane Central Register of Controlled Trials. Seven evaluable randomised clinical trials (RCTs) were identified and analysed. Primary outcomes included the duration of antibiotic therapy for the first episode of infection and 28-day mortality. Secondary outcomes included length of ICU stay, length of hospitalisation, antibiotic-free days within the first 28 days of hospitalisation, recurrences, and superinfections. RESULTS: Data on the duration of antibiotic therapy for the first episode of infection were provided in five out of seven included RCTs, while data on 28-day mortality were provided in all of the included RCTs. Duration of antibiotic therapy for the first episode of infection was reduced in favour of PCT-guided treatment [pooled weighted mean difference (WMD) = -3.15 days, random effects model, 95 % confidence interval (CI) -4.36 to -1.95, P < 0.001]. There was no difference in 28-day mortality between the compared arms [fixed effect model (FEM), odds ratio = 0.96, 95 % CI 0.79-1.15, P = 0.63). Antibiotic-free days were increased within the first 28 days of hospitalisation in favour of the PCT-guided treatment arm (pooled WMD = 3.08 days, FEM, 95 % CI 2.06-4.10, P < 0.001). No difference was found regarding the remaining outcomes. Sensitivity analyses including studies of higher quality and studies using the TRACE method to measure PCT yielded similar results. CONCLUSIONS: Procalcitonin-guided antibiotic therapy algorithms could help in reducing the duration of antimicrobial administration without having a negative impact on survival.

Triple valve endocarditis as an unusual complication of bacterial meningitis.

We report a case of Staphylococcus aureus endocarditis with late onset in a 39-year-old male drug abuser, who presented with bacterial meningitis. Despite resolution of the meningitis as the result of appropriate antimicrobial chemotherapy he developed triple valve endocarditis. Some striking features of this case and a comparison with other reported cases of this uncommon presentation of infective endocarditis are discussed.

Primary right atrium angiosarcoma mimicking pericarditis.

BACKGROUND: Primary cardiac neoplasms occur rarely and most of them are benign. Malignant tumors including angiosarcoma are extremely rare and have a non specific clinical presentation and a poor prognosis. CASE PRESENTATION: We present a case of a young male who was transferred to our hospital because of shock and multiple organ failure after a complicated pericardial biopsy. During the previous seven months he presented with recurrent episodes of pericardial effusions and tamponade. Chest computed tomography revealed a mass in the right atrium, infiltrating the myocardium and pericardium. During emergency surgery that followed, the patient died because of uncontrolled hemorrhage. Autopsy revealed the mass of the right atrium, which was identified on histological examination as primary cardiac angiosarcoma. CONCLUSION: This case highlights the difficulties both in early diagnosis and in the management of patients with cardiac angiosarcoma.

Fatal post-traumatic zygomycosis in an immunocompetent young patient.

Zygomycosis, a relatively uncommon infection, usually occurs among immunocompromised individuals. It has been reported only rarely in trauma patients. A fatal case is reported of pulmonary and rapidly progressive cutaneous zygomycosis in a young, otherwise healthy farmer, with multiple bone fractures, wounds and soft tissue injuries after an accident with an agricultural machine in the field. Rhizopus spp. was isolated from both cultures of bronchial washings and wound samples. The diagnosis was confirmed by histopathological examination of tissue specimens from a large wound. Despite systemic antifungal therapy and surgical debridement, the patient's condition deteriorated and he died from refractory septic shock.

Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: a lethal cause of pneumonia in an adult immunocompetent patient.

Necrotizing pneumonia and fatal septic shock were caused by Panton-Valentine leukocidin-positive, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in a previously healthy, 61-y-old female. This patient did not belong to any high-risk group (e.g. homosexuals, military recruits, sports team members, etc.). CA-MRSA infection should be suspected in any adult with severe pneumonia/sepsis.

Kinetics of progenitor hemopoetic stem cells in sepsis: correlation with patients survival?

BACKGROUND: Current theories underline the crucial role of pro-inflammatory mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes derive from progenitor hemopoetic cells, the kinetics of stem cells was studied in peripheral blood of patients with sepsis. METHODS: Blood was sampled from 44 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA. CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti-CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight healthy volunteers served as controls. RESULTS: Median of CD34/CD45 absolute count of controls was 1.0/mul. Respective values of the total study population were 123.4, 112.4, 121.5 and 120.9/mul on days 1, 3, 5 and 7 (p < 0.0001 compared to controls). Positive correlations were found between the absolute CD34/CD45 count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged among patients with less than 310/microl CD34/CD45 cells on day 1 compared to those with more than 310/microl of CD34/CD45 cells (p: 0.022). Hazard ratio for death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/microl. Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with less than 310/microl and more than 310/microl CD34/CD45 cells (p: 0.021). CONCLUSION: Stem cells are increased in peripheral blood over all days of follow-up compared to healthy volunteers. Patients with counts on day 1 less than 310/microl are accompanied by increased survival compared to patients with more than 310/microl.