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1.
Immunity ; 54(4): 753-768.e5, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33765435

ABSTRACT

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.


Subject(s)
Immunity/genetics , Virus Diseases/immunology , Antigen Presentation/genetics , Cohort Studies , Hematopoiesis/genetics , Humans , Interferons/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Myeloid Cells/immunology , Myeloid Cells/pathology , Prognosis , Severity of Illness Index , Systems Biology , Transcriptome , Virus Diseases/blood , Virus Diseases/classification , Virus Diseases/genetics , Viruses/classification , Viruses/pathogenicity
2.
Elife ; 102021 03 08.
Article in English | MEDLINE | ID: mdl-33682678

ABSTRACT

Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme. Clinical trial number: NCT04357366.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Respiratory Insufficiency/prevention & control , Aged , Aged, 80 and over , Antigens, CD/blood , Antigens, Differentiation, Myelomonocytic/blood , COVID-19/mortality , Female , Humans , Incidence , Injections, Subcutaneous , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Receptors, Cell Surface/blood , Receptors, Urokinase Plasminogen Activator/blood , Receptors, Urokinase Plasminogen Activator/metabolism , Respiration, Artificial , Respiratory Insufficiency/epidemiology , SARS-CoV-2 , Standard of Care , Treatment Outcome
3.
Folia Med (Plovdiv) ; 62(3): 444-452, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-33009738

ABSTRACT

Tuberculosis is a severe, infectious disease caused by Mycobacterium tuberculosis. The aim of this review was to present the efficacy of linezolid as an agent against multidrug and extensively drug-resistant tuberculosis as gathered from many recent research studies. Linezolid seems to have strongly the potential of being used as an anti-tuberculosis agent because it blocks bacterial ribosomal protein synthesis. Nevertheless caution is required because of the adverse effects it causes, especially when the linezolid daily dosage exceeds 600 mg. The most severe adverse effects include anemia, peripheral neuropathy, optic neuropathy and thrombocytopenia. Still, more trials and research need to be done in order to gather more information and value the cost-benefit dosage of the treatment.


Subject(s)
Antitubercular Agents , Extensively Drug-Resistant Tuberculosis , Linezolid , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/adverse effects , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Humans , Linezolid/adverse effects , Linezolid/pharmacology , Linezolid/therapeutic use
4.
J Clin Virol ; 131: 104608, 2020 10.
Article in English | MEDLINE | ID: mdl-32877891

ABSTRACT

OBJECTIVES: Measles outbreaks are increasingly reported among countries that were close-to-eliminate measles infection. There are few reports of clinical characteristics of measles in adults in the contemporary literature. In this study we aim to describe the clinical characteristics and complications of measles infection in hospitalized adults during the recent epidemic in Greece. METHODS: A multicentre observational retrospective study was conducted in three tertiary hospitals in Greece. All adult hospitalized patients (≥18 years old) with serologically confirmed and/or clinical features compatible with measles were included. Pediatric patients and patients with missing data were excluded. RESULTS: In total, 93 patients, 40 males (43 %) and 53 females (57 %), mostly young patients were included. Most of them (87 %) had no past medical history. Among women, 4 were pregnant. 56 (60.2 %) and 25 (26.9 %) patients reported either unknown or incomplete vaccination for measles. Ribavirin was administered in 8 (8.6 %) patients. Pneumonitis and hepatic involvement were the most common complications, occurring in 43 (46.2 %) and 75 (80.6 %) patients respectively. Pneumonitis was significantly associated with male sex, older age, lower lymphocyte counts and higher C-reactive protein (CRP) on admission. One pregnant woman suffered spontaneous fetal miscarriage and one patient died due to acute respiratory distress syndrome (ARDS) and high-risk pulmonary embolism. CONCLUSION: Considerable proportions of incompletely vaccinated or unvaccinated adults have led to the re-emergence of measles in countries with reported close-to-elimination rates. Pneumonitis is a major complication among adults with measles. More studies are imperative in order to explore the role of immune paresis in measles.


Subject(s)
Hospitalization/statistics & numerical data , Measles/diagnosis , Measles/epidemiology , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , Adolescent , Adult , Antiviral Agents/therapeutic use , Female , Greece/epidemiology , Humans , Liver Diseases/epidemiology , Liver Diseases/etiology , Male , Measles/complications , Measles/drug therapy , Measles virus , Middle Aged , Pneumonia/epidemiology , Pneumonia/etiology , Pregnancy , Retrospective Studies , Ribavirin/therapeutic use , Risk Factors , Treatment Outcome , Vaccination/statistics & numerical data , Young Adult
5.
Gastroenterol Hepatol Bed Bench ; 13(3): 219-222, 2020.
Article in English | MEDLINE | ID: mdl-32821351

ABSTRACT

Aim: To estimate the cost per patient for hepatocellular carcinoma in Greece, a setting that is currently facing financial constraints. Background: Hepatocellular carcinoma patient management strategies are associated with significant costs. Despite this, patient level data on healthcare resource use and cost-of-illness analyses of hepatocellular carcinoma remain rather scarce in the international literature. Methods: 123 patients diagnosed with hepatocellular carcinoma and followed in a specialised clinic of a tertiary hospital in Greece formed the basis of the analysis. Detailed resource use data were derived from the medical records of each patient. Data were recorded from the first encounter of the patient with the facility until a fatal endpoint or until the last day of follow up. Patients that were lost to follow-up were excluded from the analysis. Calculations follow a third-party payer perspective, according to official prices and tariffs. Results: The average cost per patient was estimated at 12,119.1 Euros (SD: 14,670.3) (21,375.1 PPP USD) for the average follow-up period and 10,241.5 Euros (18,063.5 PPP USD) per year. Median costs per month of follow-up according to underlying disease were 1,218.1, 1,376.8, 1,521.3 and 686.9 Euros (2,148.4, 2,428.3, 2,683.2 and 1,211.5 PPP USD) for patients with alcoholic steatohepatitis, hepatitis B, hepatitis C and non-alcoholic fatty liver disease, respectively. Conclusion: Hepatocellular carcinoma represents a heavy toll, both from the clinical as well as from the economic perspective, especially for a setting in "dire straits". Interventions towards reducing the incidence and, subsequently, the cost of HCC are imperative.

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