Predicting the next pandemic: VACCELERATE ranking of the World Health Organization's Blueprint for Action to Prevent Epidemics

Introduction: The World Health Organization (WHO)'s Research and Development (R&D) Blueprint for Action to Prevent Epidemics, a plan of action, highlighted several infectious diseases as crucial targets for prevention. These infections were selected based on a thorough assessment of factors such as transmissibility, infectivity, severity, and evolutionary potential. In line with this blueprint, the VACCELERATE Site Network approached infectious disease experts to rank the diseases listed in the WHO R&D Blueprint according to their perceived risk of triggering a pandemic. VACCELERATE is an EU-funded collaborative European network of clinical trial sites, established to respond to emerging pandemics and enhance vaccine development capabilities. Methods: Between February and June 2023, a survey was conducted using an online form to collect data from members of the VACCELERATE Site Network and infectious disease experts worldwide. Participants were asked to rank various pathogens based on their perceived risk of causing a pandemic, including those listed in the WHO R&D Blueprint and additional pathogens. Results: A total of 187 responses were obtained from infectious disease experts representing 57 countries, with Germany, Spain, and Italy providing the highest number of replies. Influenza viruses received the highest rankings among the pathogens, with 79 % of participants including them in their top rankings. Disease X, SARS-CoV-2, SARS-CoV, and Ebola virus were also ranked highly. Hantavirus, Lassa virus, Nipah virus, and henipavirus were among the bottom-ranked pathogens in terms of pandemic potential. Conclusion: Influenza, SARS-CoV, SARS-CoV-2, and Ebola virus were found to be the most concerning pathogens with pandemic potential, characterised by transmissibility through respiratory droplets and a reported history of epidemic or pandemic outbreaks

Prevention of influenza viral pneumonia using zanamivir and antisense oligonucleotide against inducible nitric oxide synthase

Currently used medications against influenza do not always prevent the complications of the disease, and the increasing number of drug-resistant influenza virus subtypes is observed. Therefore, new drugs are needed to prevent the direct cytopathic effect of virus and suppress the inflammatory mediators. The aim of this study - to evaluate if zanamivir and/or antisense oligonucleotide against inducible nitric oxide synthase prevents influenza viral pneumonia. During the experiment, the mice were infected with the influenza virus and treated with zanamivir, antisense oligonucleotide against iNOS or a combination of both. The mice were weighed daily. After 3-5 days, the mice were killed, the lung excised, the bronchoalveolar lavage was performed for the nitrite determination. Mouse lung histological analyse was performed and the relative level of influenza RNA, cytokines IFN-γ and TNF-α and iNOS iRNA was assessed by the RT-PCR. The study demonstrated several new findings. First, that treatment with zanamivir posesses the early capacity to suppress NO synthesis in mouse lungs after influenza infection. Second, that treatment with antisense oligodeoxynucleotide to iNOS mRNA can reduce lung inflammation caused by influenza virus infection in mice, and its combination with zanamivir has clinical benefit; thus, this treatment approach could be a potential new option in the treatment of influenza virus infection

Gripo virusinės pneumonijos prevencija naudojant zanamivirą ir priešprasminį oligonukleotidą prieš indukuojamą azoto oksido sintazę

Currently used medications against influenza do not always prevent the complications of the disease, and the increasing number of drug-resistant influenza virus subtypes is observed. Therefore, new drugs are needed to prevent the direct cytopathic effect of virus and suppress the inflammatory mediators. The aim of this study - to evaluate if zanamivir and/or antisense oligonucleotide against inducible nitric oxide synthase prevents influenza viral pneumonia. During the experiment, the mice were infected with the influenza virus and treated with zanamivir, antisense oligonucleotide against iNOS or a combination of both. The mice were weighed daily. After 3-5 days, the mice were killed, the lung excised, the bronchoalveolar lavage was performed for the nitrite determination. Mouse lung histological analyse was performed and the relative level of influenza RNA, cytokines IFN-γ and TNF-α and iNOS iRNA was assessed by the RT-PCR. The study demonstrated several new findings. First, that treatment with zanamivir posesses the early capacity to suppress NO synthesis in mouse lungs after influenza infection. Second, that treatment with antisense oligodeoxynucleotide to iNOS mRNA can reduce lung inflammation caused by influenza virus infection in mice, and its combination with zanamivir has clinical benefit; thus, this treatment approach could be a potential new option in the treatment of influenza virus infection

The association between COVID-19 infection and kidney damage in a regional university hospital

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman’s correlation coefficient = −0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die

A rare case of tularemia complicated by rhabdomyolysis with a successful outcome

We present a case of tularemia complicated by rhabdomyolysis in a 43-year-old male who presented with fever, swelling, and pain of the right groin and a history of a week-old tick bite. Empirical parenteral amoxicillin/clavulanic acid treatment was initiated. Suspecting tularemia, parenteral gentamycin was added. Later, the patient started to complain of muscle pain, weakness, and difficulties in breathing and walking. Heightened levels of creatine kinase and myoglobin concentration (42,670 IU/L and >12,000 μg/L, respectively) were found. Due to rhabdomyolysis, large amounts of intravenous fluid therapy were initiated to prevent kidney damage, continuing intravenous antibiotic therapy. Francisella tularensis IgG in serum was found to be positive only on the sixteenth day of hospitalization. Upon discharge, the laboratory analyses returned to normal levels, and the patient was in good condition. The successful outcome could be associated with the early appropriate therapy of tularemia and its rare complication of rhabdomyolysis

Predictors of Noninvasive Respiratory Support Failure in COVID-19 Patients: A Prospective Observational Study

Background and Objective: Respiratory assistance tactic that is best for COVID-19-associated acute hypoxemic respiratory failure (AHRF) individuals has yet to be determined. Patients with AHRF may benefit from the use of a high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The goals of this prospective observational research were to estimate predictive factors for HFNC and NIV failure in COVID-19-related AHRF subjects. Materials and Methods: The research enlisted the participation of 124 patients. A stepwise treatment approach was used. HFNC and NIV were used on 124 (100%) and 64 (51.6%) patients, respectively. Thirty (24.2%) of 124 patients were intubated and received invasive mechanical ventilation. Results: 85 (68.5%) patients were managed successfully. Patients who required NIV exhibited a higher prevalence of treatment failure (70.3% vs. 51.6%, p = 0.019) and had higher mortality (59.4% vs. 31.5%, p = 0.001) than patients who received HFNC. Using logistic regression, the respiratory rate oxygenation (ROX) index at 24 h (odds ratio (OR) = 0.74, p = 0.018) and the Charlson Comorbidity Index (CCI) (OR = 1.60, p = 0.003) were found to be predictors of HFNC efficacy. It was the ROX index at 24 h and the CCI optimum cut-off values for HFNC outcome that were 6.1 (area under the curve (AUC) = 0.73) and 2.5 (AUC = 0.68), respectively. Serum ferritin level (OR = 0.23, p = 0.041) and lymphocyte count (OR = 1.03, p = 0.01) were confirmed as predictors of NIV failure. Serum ferritin level at a cut-off value of 456.2 ng/mL (AUC = 0.67) and lymphocyte count lower than 0.70 per mm3, (AUC = 0.70) were associated with NIV failure with 70.5% sensitivity, 68.7% specificity and sensitivity of 84.1%, specificity of 56.2%, respectively. Conclusion: The ROX index at 24 h, CCI, as well as serum ferritin level, and lymphocyte count can be used as markers for HFNC and NIV failure, respectively, in SARS-CoV-2-induced AHRF patients

Pulmonary Coccidioidomycosis: A Case Report and Literature Review

Coccidioidomycosis is an infectious disease caused by Coccidioides immitis or C. posadasii fungus. Humans usually get infected by inhaling spores risen from the soil. Although in 60 percent of cases symptoms are absent, remaining patients can develop various manifestations of the disease, from flu-like symptoms to severe dissemination or meningitis. In endemic regions (California, Arizona, Mexico, Central, and South America), pulmonary coccidioidomycosis causes 25% of community-acquired cases of pneumonia. We present the first registered case of pulmonary coccidioidomycosis in Lithuania. Clinical presentation, pathogenesis, treatment options, and diagnostic alternatives are discussed