Investigational Use of Mesenchymal Stem/Stromal Cells and Their Secretome as Add-On Therapy in Severe Respiratory Virus Infections: Challenges and Perspectives.

Serious manifestations of respiratory virus infections such as influenza and coronavirus disease 2019 (COVID-19) are associated with a dysregulated immune response and systemic inflammation. Treating the immunological/inflammatory dysfunction with glucocorticoids, Janus kinase inhibitors, and monoclonal antibodies against the interleukin-6 receptor has significantly reduced the risk of respiratory failure and death in hospitalized patients with severe COVID-19, but the proportion of those requiring invasive mechanical ventilation (IMV) and dying because of respiratory failure remains elevated. Treatment of severe influenza-associated pneumonia and acute respiratory distress syndrome (ARDS) with available immunomodulators and anti-inflammatory compounds is still not recommended. New therapies are therefore needed to reduce the use of IMV and the risk of death in hospitalized patients with rapidly increasing oxygen demand and systemic inflammation who do not respond to the current standard of care. This paper provides a critical assessment of the published clinical trials that have tested the investigational use of intravenously administered allogeneic mesenchymal stem/stromal cells (MSCs) and MSC-derived secretome with putative immunomodulatory/antiinflammatory/regenerative properties as add-on therapy to improve the outcome of these patients. Increased survival rates are reported in 5 of 12 placebo-controlled or open-label comparative trials involving patients with severe and critical COVID-19 and in the only study concerning patients with influenza-associated ARDS. Results are encouraging but inconclusive for the following reasons: small number of patients tested in each trial; differences in concomitant treatments and respiratory support; imbalances between study arms; differences in MSC source, MSC-derived product, dosing and starting time of the investigational therapy; insufficient/inappropriate reporting of clinical data. Solutions are proposed for improving the clinical development plan, with the aim of facilitating regulatory approval of the MSC-based investigational therapy for life-threatening respiratory virus infections in the future. Major issues are the absence of a biomarker predicting responsiveness to MSCs and MSC-derived secretome and the lack of pharmacoeconomic evaluations.

Comparing Clinical Outcomes of COVID-19 and Influenza-Induced Acute Respiratory Distress Syndrome: A Propensity-Matched Analysis.

Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5-4.2, p < 0.001), longer mean length of stay (18.7 days vs. 14.5 days, p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5-4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3-2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19.

Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023.

This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.

Same but Different-ECMO in COVID-19 and ARDS of Other Etiologies. Comparison of Survival Outcomes and Management in Different ARDS Groups.

Background: COVID-19 has led to increased numbers of patients in need of venovenous extracorporeal membrane oxygenation (ECMO) support, but knowledge on management in comparison to acute respiratory distress syndrome (ARDS) of other etiologies is still lacking. We analyzed venovenous ECMO management and survival outcomes in patients with COVID-19 in comparison to influenza ARDS and pulmonary ARDS of other origin. Results: Retrospective analysis of prospective venovenous ECMO registry-based data collection was performed. One hundred consecutive venovenous ECMO patients with severe ARDS were included (41 COVID-19, 24 influenza A, 35 ARDS of other etiologies). Patients with COVID-19 had higher BMI (body mass index), lower SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, lower C-reactive protein and procalcitonin levels and less vasoactive support at ECMO initiation. Significantly more patients were mechanically ventilated for more than 7 days prior to ECMO initiation in the COVID-19 group, however they were ventilated with lower tidal volumes and more often received additional rescue therapies prior to and on ECMO. COVID-19 patients had significantly more barotrauma and thrombotic events on ECMO. There were no differences in weaning of ECMO, however duration of ECMO runs and ICU length of stay was significantly longer in the COVID-19 group. The leading cause of death in the COVID-19 group was irreversible respiratory failure, while uncontrolled sepsis and multiorgan failure were leading causes in the other 2 groups. All patients who survived ICU treatment were discharged out of hospital, and there were no differences in survival among groups at 180 days. Conclusions: Survival outcomes of venovenous ECMO patients do not differ between COVID-19 and ARDS of other pulmonary etiologies. ARDS guidelines were in greater proportion adhered to in COVID-19 patients, with, however, longer time to ECMO initiation. COVID-19 ARDS seems specific as a more single-organ disease with longer ECMO duration and irreversible respiratory failure as a main cause of ICU mortality.

Comparing the Cytokine Storms of COVID-19 and Pandemic Influenza.

Emerging respiratory viruses are major health threats due to their potential to cause massive outbreaks. Over the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has caused millions of cases of severe infection and deaths worldwide. Although natural and vaccine-induced protective immune mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been increasingly identified, the factors that determine morbimortality are less clear. Comparing the immune signatures of COVID-19 and other severe respiratory infections such as the pandemic influenza might help dissipate current controversies about the origin of their severe manifestations. As such, identifying homologies in the immunopathology of both diseases could provide targets for immunotherapy directed to block shared pathogenic mechanisms. Meanwhile, finding unique characteristics that differentiate each infection could shed light on specific immune alterations exploitable for diagnostic and individualized therapeutics for each case. In this study, we summarize immunopathological aspects of COVID-19 and pandemic influenza from the perspective of cytokine storms as the driving force underlying morbidity. Thereby, we analyze similarities and differences in the cytokine profiles of both infections, aiming to bring forward those molecules more attractive for translational medicine and drug development.

Antigenic Characterization of Human Monoclonal Antibodies for Therapeutic Use against H7N9 Avian Influenza Virus.

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,500 human infections and the culling of millions of poultry. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the hemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14, and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing an alanine-to-threonine substitution at residue 125 (A125T), a glycine-to-glutamic acid substitution at residue 133 (G133E), an asparagine-to-aspartic acid substitution at residue 149 (N149D), or a leucine-to-glutamine substitution at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by a hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here, we showed that the L4A-14 mAb had broad neutralizing capabilities, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both postinfection and antigen-induced sera. Therefore, the L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic applications. IMPORTANCE Avian influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have proven useful for the treatment of severe influenza infections in humans; however, concerns have been raised as antiviral-resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.

COVID-19 and seasonal influenza infection outcomes in the ICU: a retrospective comparison study.

OBJECTIVE: To compare the characteristics and outcomes of critically ill patients admitted to the intensive care unit (ICU) due to COVID-19 or influenza- associated pneumonia. PATIENTS AND METHODS: We conducted a two-center retrospective study on patients admitted to the ICU due to either COVID-19 associated pneumonia (CAP) or influenza-associated pneumonia (IAP). Baseline characteristics, therapy during hospitalization and clinical outcomes were assessed. RESULTS: Our study included 86 patients admitted to the ICU. Twenty-four patients (28%) had IAP and 62 patients (72%) had CAP. Those with IAP had more comorbidities of cardiac disease (p=0.005) and chronic obstructive lung disease (p=0.03) compared to those with CAP. Non-invasive ventilation was used significantly more in patients with IAP (p=0.001). The use of neuromuscular blockade was significantly higher in CAP patients (p=0.001). CAP patients had less favourable ventilation parameters. PEEP was significantly higher in those with CAP on the first day of admission (p=0.002). There was no difference in mortality (p=0.61) between the groups. CONCLUSIONS: Patients admission to the ICU with CAP had less comorbidity than those with IAP. Patients with CAP had poorer ventilatory parameters patterns, requiring more aggressive ventilation and ECMO support. The overall mortality did not differ significantly between the groups.

Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: A descriptive retrospective study in Japan.

Evidence suggests that older people aged ≥65 years and those aged 60-64 years with chronic medical conditions are at higher risk of developing severe complications due to influenza virus infection when compared with young, healthy adults. Although seasonal influenza is monitored through a nationwide passive surveillance in Japan, influenza related outcomes and medical resource consumption have not been fully documented. This retrospective database study aimed to describe the epidemiological and clinical characteristics of medically attended influenza cases aged ≥60 years and the associated medical resource consumption in Japan. We used clinically diagnosed influenza (CDI) based on the international classification of disease codes, and laboratory-confirmed influenza (LCI) based on influenza test results, to identify the patient population during a total of nine seasons (2010/2011 to 2018/2019). A total of 372,356 CDI and 31,122 LCI cases were identified from 77 medical institutions. The highest numbers of medically-attended influenza episodes were in patients aged 65-74 years and 75-84 years. On average, across seasons, 5.9% of all-cause hospitalizations were attributable to CDI and 0.4% were LCI. Influenza viruses type A and B co-circulated annually in varying degree of intensity and were associated with similar level of complications, including cardiovascular-related. Oxygen therapy increased with age; by contrast, mechanical ventilation, dialysis, blood transfusion, and intensive care unit admission were higher in the younger groups. In-hospital mortality for inpatients aged ≥ 85 years with CDI and LCI were 18.6% and 15.5%, respectively. Considering the burden associated with medically-attended influenza in this population, influenza prevention, laboratory confirmation and clinical management should be emphasized by general practicians and specialists like cardiologists to protect this aging population.

A comparative analysis of the outcomes of patients with influenza or COVID-19 in a tertiary hospital in Belgium.

INTRODUCTION: The COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium. METHODS: In this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO. RESULTS: Based on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: -0.10, 95% CI: 0.15 to -0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%). CONCLUSIONS: COVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.

Characteristics and Results of Hospital Admission Caused by Influenza Virus Infections in Children under 5 Years Old.

AIMS: The influenza virus is an infectious disease with acute respiratory tract infections, caused secondary bacterial infections and death. In this study, we aimed to determine which predictors were associated with the need for high-flow nasal cannula oxygen therapy (HFNC) and transition to intensive care for influenza virus and also to compare single viral pathogens with multiple ones. METHODS: Inpatients under the age of 5 with influenza virus-related respiratory tract infections between November 2015 and March 2019 were included in the study. Demographic features, comorbidities, symptoms, secondary bacterial infection, need for HFNC and pediatric intensive care unit and respiratory support system, length of hospital stay, polymerase chain reaction tests were recorded. RESULTS: A total of 93 patients were included in the study. It was determined that 53.8% of the cases were male and 84.9% were under the age of 2. Comorbidities were present in 50.5% of the cases. Secondary bacterial pneumonia developed in 56.9% of the cases. Patients with secondary bacterial pneumonia had higher PICU need, HFNC need and hospital stay (p = 0.014, p ≤ 0.001 and p ≤ 0.001, respectively). Patients with comorbidity had longer hospital stays and a higher need for HFNC (p ≤ 0.001 and p = 0.001, respectively). CONCLUSIONS: In this study, it was determined that especially comorbidity and secondary bacterial infection aggravated the clinical treatment of hospitalized patients. Therefore, it was concluded that patients with comorbidity should be followed closely and secondary bacterial pneumonia should be recognized and treated early.

Natural Alternatives and the Common Cold and Influenza.

The use of complementary and integrative medicine has increased . It is estimated that one-third of the population of the United States uses some form of alternative medicine. Physicians should consider integrative medicine therapies . Alternative medical therapies for the common cold and influenza include herbal supplements, dietary supplements, diet, and other adjunct therapies. However, it is important to research and study these therapies. Therefore, communication with patients and other health care providers is important. This will ensure effective and positive patient care experiences. Further randomized clinical trials are necessary to further establish the role of various alternative options.

Severe influenza A in a Tunisian ICU sentinel SARI centre: Epidemiological and clinical features.

INTRODUCTION: Influenza A virus infection is a contagious acute respiratory infection which mostly evolves in an epidemic form, less frequently as pandemic outbreaks. It can take a severe clinical form that needs to be managed in intensive care unit (ICU). The aim of this study was to describe the epidemiological and clinical aspects of influenza A, then to determine independent predictive factors of ICU mortality in Abderrahmen Mami hospital, Ariana, Tunisia. METHODS: It was a single-center study, including all hospitalized patients in intensive care, between November 1st, 2009 and October 31st, 2019, with influenza A virus infection. We recorded demographic, clinical and biological data, evolving features; then multivariate analysis of the predictive factors of ICU mortality was realized. RESULTS: During the study period (10 consecutive seasons), 120 patients having severe Influenza A were admitted (Proportion = 2.5%) from all hospitalized patients, with a median age of 48 years and a gender-ratio of 1.14. Among women, 14 were pregnant. Only 7 patients (5.8%) have had seasonal flu vaccine during the year before ICU admission. The median values of the Simplified Acute Physiology Score II, Acute Physiologic and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment were respectively 26, 10 and 3. Virus strains identified with polymerase chain reaction were H1N1 pdm09 (84.2%) and H3N2 (15.8%). Antiviral therapy was prescribed in 88 (73.3%) patients. A co-infection was recorded in 19 cases: bacterial (n = 17) and aspergillaire (n = 2). An acute respiratory distress syndrome (ARDS) was diagnosed in 82 patients. Non-invasive ventilation (NIV) was conducted for 72 (60%) patients with success in 34 cases. Endotracheal intubation was performed in 59 patients with median duration of invasive mechanical ventilation 8 [3.25-13] days. The most frequent complications were acute kidney injury (n = 50, 41.7%), shock (n = 48, 40%), hospital-acquired infections (n = 46, 38.8%) and thromboembolic events (n = 19, 15.8%). The overall ICU mortality rate was of 31.7% (deceased n = 38). Independent predictive factors of ICU mortality identified were: age above 56 years (OR = 7.417; IC95% [1.474-37.317]; p = 0.015), PaO2/FiO2 ≤ 95 mmHg (OR = 9.078; IC95% [1.636-50.363]; p = 0.012) and lymphocytes count ≤ 1.325 109/L (OR = 10.199; IC95% [1.550-67.101]; p = 0.016). CONCLUSION: Influenza A in ICU is not uncommon, even in A(H1N1) dominant seasons; its management is highly demanding. It is responsible for considerable morbi-mortality especially in elderly patients.

Extracorporeal membrane oxygenation for the treatment of ARDS in Covid-19 and influenza patients: Does etiology matter?

At the beginning of the COVID 19 pandemic, the outcome of patients treated with ECMO was discouraging. Subsequently, it became clear that a certain group of patients may benefit from ECMO treatment. The primary objective of this study was to compare the outcome of ECMO treatment in COVID-19 and influenza patients referred to a tertiary care center. A total of 119 adult patients required ECMO treatment following ARDS secondary to H1N1 (49) and SARS-CoV-2 (70) in the referral ECMO Center based in Zagreb between October 2009 and October 2021. Our study revealed a significantly higher mortality in COVID-19 patients compared to H1N1 influenza when the onset of ARDS was severe enough to require ECMO support. Based on these results and current knowledge, we argue that ECMO treatment for ARDS in COVID-19 patients is more challenging compared to H1N1 influenza patients. Therefore, referral to the most experienced ECMO centers should be considered. Additionally, patient selection and timing for ECMO treatment play a key role in relation to outcome. Mortality rate in COVID-19 patients requiring ECMO treatment may be used as a reference frame for ECMO centers to ensure best possible care and outcome.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges.

The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies. We outline multidisciplinary approaches and technological innovations that need to be harnessed in order to improve preparedeness to the next pandemic.

COVID-19, Influenza and RSV: Surveillance-informed prevention and treatment - Meeting report from an isirv-WHO virtual conference.

The International Society for Influenza and other Respiratory Virus Diseases (isirv) and the WHO held a joint virtual conference from 19th-21st October 2021. While there was a major focus on the global response to the SARS-CoV-2 pandemic, including antivirals, vaccines and surveillance strategies, papers were also presented on treatment and prevention of influenza and respiratory syncytial virus (RSV). Potential therapeutics for SARS-CoV-2 included host-targeted therapies baricitinib, a JAK inhibitor, tocilizumab, an IL-6R inhibitor, verdinexor and direct acting antivirals ensovibep, S-217622, AT-527, and monoclonal antibodies casirivimab and imdevimab, directed against the spike protein. Data from trials of nirsevimab, a monoclonal antibody with a prolonged half-life which binds to the RSV F-protein, and an Ad26.RSV pre-F vaccine were also presented. The expanded role of the WHO Global Influenza Surveillance and Response System to address the SARS-CoV-2 pandemic was also discussed. This report summarizes the oral presentations given at this meeting for the benefit of the broader medical and scientific community involved in surveillance, treatment and prevention of respiratory virus diseases.

Comparison of clinical and biochemical features of hospitalized COVID-19 and influenza pneumonia patients.

Both severe acute respiratory syndrome coronavirus 2 and influenza viruses cause similar clinical presentations. It is essential to assess severely ill patients presenting with a viral syndrome for diagnostic and prognostic purposes. We aimed to compare clinical and biochemical features between pneumonia patients with coronavirus disease 2019 (COVID-19) and H1N1. Sixty patients diagnosed with COVID-19 pneumonia and 61 patients diagnosed with influenza pneumonia were hospitalized between October 2020-January 2021 and October 2017-December 2019, respectively. All the clinical data and laboratory results, chest computed tomography scans, intensive care unit admission, invasive mechanical ventilation, and outcomes were retrospectively evaluated. The median age was 65 (range 32-96) years for patients with a COVID-19 diagnosis and 58 (range 18-83) years for patients with influenza (p = 0.002). The comorbidity index was significantly higher in patients with COVID-19 (p = 0.010). Diabetes mellitus and hypertension were statistically significantly more common in patients with COVID-19 (p = 0.019, p = 0.008, respectively). The distribution of severe disease and mortality was not significantly different among patients with COVID-19 than influenza patients (p = 0.096, p = 0.049).). In comparison with inflammation markers; C-reactive protein (CRP) levels were significantly higher in influenza patients than patients with COVID-19 (p = 0.033). The presence of sputum was predictive for influenza (odds ratio [OR] 0.342 [95% confidence interval [CI], 2.1.130-0.899]). CRP and platelet were also predictive for COVID-19 (OR 4.764 [95% CI, 1.003-1.012] and OR 0.991 [95% CI 0.984-0.998], respectively. We conclude that sputum symptoms by itself are much more detected in influenza patients. Besides that, lower CRP and higher PLT count would be discriminative for COVID-19.

Emergency preparedness, resilience and response to a biological outbreak.

Major disease outbreaks continue to be a significant risk to public health, with pandemic influenza or an emerging infectious disease outbreak at the top of the UK National Risk Register. The risk of deliberate release of a biological agent is lower but remains possible and may only be recognised after casualties seek medical attention. In this context the emergency preparedness, resilience and response (EPRR) process protects the public from high consequence infectious diseases, other infectious disease outbreaks and biological agent release. The core elements of the EPRR response are recognition of an outbreak, isolation of patients, appropriate personal protective equipment for medical staff and actions to minimise further disease spread. The paper discusses how high-threat agents may be recognised by clinicians, the initial actions to be taken on presentation and how the public health system is notified and responds. It draws on the national pandemic influenza plans to describe the wider response to a major disease outbreak and discusses training requirements and the potential role of the military.

A systematic review and meta-analysis comparing the clinical characteristics and outcomes of COVID-19 and influenza patients on ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. METHODS: We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. RESULTS: The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups. CONCLUSION: Clinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.