Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.

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.

Immunogenicity and safety of vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis. METHODS: MEDLINE(PubMed) and Cochrane databases were searched based on a pre-specified protocol (PROSPERO: CRD42020202018). Studies reporting on patients with MS, diagnosed with McDonald criteria getting vaccinated with any type of vaccine were included in the analysis. The primary endpoint was the incidence of patients being seropositive and experience adverse events after vaccination. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Two reviewers independently screened and reviewed existing literature and assessed study quality with the Methodological index for non-randomized studies. RESULTS: Of 295 articles, 45 studies were analyzed. Seroconversion after COVID-19 vaccines was 76% (95% CI, 70-80; I2 = 95%; 20 studies including 5601 patients. Protection was lower in patients treated with anti-CD20 antibodies and sphingosine-1-phosphate receptor (S1PR) modulators compared to untreated patients or treatment with other DMTs. Relapse occurred in 2% (95% CI, 1-3; I2 = 86%; 16 studies including 7235 patients). Seroconversion after seasonal influenza vaccines was 82% (95% CI, 65-91; I2 = 90%; 6 studies including 490 patients). Relapse rate was similar to this after COVID-19 vaccination. CONCLUSION: The majority of MS patients vaccinated for COVID-19 or seasonal influenza mount an adequate immune response without safety concerns. Data on other vaccines are limited.

Immunogenicity of a seasonal influenza and a pneumococcal polysaccharide vaccine in multiple sclerosis patients under disease modifying therapies: A single-center prospective study.

BACKGROUND: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). METHODS: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months. RESULTS: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (pMcNemar < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (pMcNemar < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination. CONCLUSIONS: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients.

An open label trial of anakinra to prevent respiratory failure in COVID-19.

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.

People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body's immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.

A cost of illness analysis of hepatocellular carcinoma for the Greek healthcare setting.

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.

Linezolid: a Promising Agent for the Treatment of Multiple and Extensively Drug-Resistant Tuberculosis.

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.

Clinical characteristics and outcomes of measles outbreak in adults: A multicenter retrospective observational study of 93 hospitalized adults in Greece.

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.