Incentivizing at‐risk production capacity building for COVID‐19 vaccines

Our study analyzes capacity management for promising vaccine candidates before regulatory approval (i.e., at‐risk capacity building) in the presence of production outsourcing and different operational challenges: misaligned interests, possible ex post negotiations, asymmetric information between developers and manufacturers, and government involvement. We develop analytical models to compare two vaccine production modes: (1) the integrated mode (a single company determines the at‐risk capacity and produces in‐house) and (2) the outsourcing mode (a manufacturer determines the at‐risk capacity and a developer determines a funding level to share the capacity‐building cost). Our study reveals that outsourcing can achieve a higher at‐risk capacity only if it can achieve sufficient cost savings compared to the integrated mode. Our research also proves that both vaccine production modes tend to underinvest in the at‐risk capacity. Following this, we suggest measures to improve the at‐risk capacity building in both vaccine production modes. Our signaling game model reveals that a developer with high competence cannot always send credible signals of its true competence level to the manufacturer. Our incomplete contract model verifies that the relative performance of the two vaccine production modes is robust when ex post negotiation occurs under the outsourcing mode;however, the two parties may show incompatible preferences for the ex post negotiation. Our study also analyzes the optimal allocation of government financial support to development funding and capacity funding to incentivize at‐risk capacity building. We present comprehensive guidelines for the different stakeholders to collectively contribute to ramping up the at‐risk capacity of promising vaccines.

Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality.

BACKGROUND: Although older adults are at high risk for severe coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission, age is often used as a selection criterion in case of ICU beds scarcity. We sought to compare the proportion, clinical features and mortality between patients ≥70 years old and younger ICU patients with COVID-19. METHODS: All patients, consecutively admitted to our COVID ICU, where age was not used as an admission criterion, from March 2020 through April 2021, were included. Demographics, clinical and laboratory characteristics were recorded. Illness severity and Charlson comorbidity Index (CCI) were calculated. Patients≥70 years old were compared to youngers. RESULTS: Of 458 patients (68 [59-76] years, 70% males), 206 (45%) were ≥70 years old. Compared to younger, older patients had higher illness severity scores (APACHE II 18 [14-23] versus 12 [9-16], P<0.001, SOFA 8 [6-10] versus 6 [2-8], P<0.001, CCI 5 [4-6] versus 2 [1-3], P<0.001), increased need for mechanical ventilation (92% vs. 72%, P<0.001) and ICU mortality (74% versus. 29%, P<0.001). Age (HR: 1.045, CI: 1.02-1.07, P=0.001), CCI (HR: 1.135, CI: 1.037-1.243, P=0.006) and APACHE II (HR: 1.070, CI: 1.013-1.130, P=0.015) were independently associated with mortality. Among comorbidities, obesity, chronic pulmonary disease and chronic kidney disease were independent risk factors for death. CONCLUSIONS: When age is not used as criterion for admission to COVID ICU, patients ≥70 years old represent a considerable proportion and, compared to younger ones, they have higher mortality. Age, severity of illness and CCI, and certain comorbidities are independent risk factors for mortality.

Incentivizing at-risk production capacity building for COVID-19 vaccines

Our study analyzes capacity management for promising vaccine candidates before regulatory approval (i.e., at-risk capacity building) in the presence of production outsourcing and different operational challenges: misaligned interests, possible ex-post negotiations, asymmetric information between developers and manufacturers, and government involvement. We develop analytical models to compare two vaccine production modes: (1) the integrated mode (a single company determines the at-risk capacity and produces in-house);and (2) the outsourcing mode (a manufacturer determines the at-risk capacity and a developer determines a funding level to share the capacity building cost). Our study reveals that outsourcing can achieve a higher at-risk capacity only if it can achieve sufficient cost savings compared with the integrated mode. Our research also proves that both vaccine production modes tend to underinvest in the at-risk capacity. Following this, we suggest measures to improve the at-risk capacity building in both vaccine production modes. Our signaling game model reveals that a developer with high competence cannot always send credible signals of its true competence level to the manufacturer. Our incomplete contract model verifies that the relative performance of the two vaccine production modes is robust when ex-post negotiation occurs under the outsourcing mode;however, the two parties may show incompatible preferences for the ex-post negotiation. Our study also analyzes the optimal allocation of government financial support to development funding and capacity funding to incentivize at-risk capacity building. We present comprehensive guidelines for the different stakeholders to collectively contribute to ramping up the at-risk capacity of promising vaccines. This article is protected by copyright. All rights reserved

Effect of COVID-19-Related Lockdown οn Hospital Admissions for Asthma and COPD Exacerbations: Associations with Air Pollution and Patient Characteristics.

We conducted a retrospective observational study to assess the hospitalization rates for acute exacerbations of asthma and COPD (chronic obstructive pulmonary disease) during the first imposed lockdown in Athens, Greece. Patient characteristics and the concentration of eight air pollutants [namely, NO (nitrogen monoxide), NO2 (nitrogen dioxide), CO (carbon monoxide), PM2.5 (particulate matter 2.5), PM10 (particulate matter 10), O3 (ozone), SO2 (sulfur dioxide) and benzene] were considered. A total of 153 consecutive hospital admissions were studied. Reduced admissions occurred in the Lockdown period compared to the Pre-lockdown 2020 (p < 0.001) or the Control 2019 (p = 0.007) period. Furthermore, the concentration of 6/8 air pollutants positively correlated with weekly hospital admissions in 2020 and significantly decreased during the lockdown. Finally, admitted patients for asthma exacerbation during the lockdown were younger (p = 0.046) and less frequently presented respiratory failure (p = 0.038), whereas patients with COPD presented higher blood eosinophil percentage (p = 0.017) and count (p = 0.012). Overall, admissions for asthma and COPD exacerbations decreased during the lockdown. This might be partially explained by reduction of air pollution during this period while medical care avoidance behavior, especially among elderly patients cannot be excluded. Our findings aid in understanding the untold impact of the pandemic on diseases beyond COVID-19, focusing on patients with obstructive diseases.

The Role of Noninvasive Respiratory Management in Patients with Severe COVID-19 Pneumonia.

Acute hypoxemic respiratory failure is the principal cause of hospitalization, invasive mechanical ventilation and death in severe COVID-19 infection. Nearly half of intubated patients with COVID-19 eventually die. High-Flow Nasal Oxygen (HFNO) and Noninvasive Ventilation (NIV) constitute valuable tools to avert endotracheal intubation in patients with severe COVID-19 pneumonia who do not respond to conventional oxygen treatment. Sparing Intensive Care Unit beds and reducing intubation-related complications may save lives in the pandemic era. The main drawback of HFNO and/or NIV is intubation delay. Cautious selection of patients with severe hypoxemia due to COVID-19 disease, close monitoring and appropriate employment and titration of HFNO and/or NIV can increase the rate of success and eliminate the risk of intubation delay. At the same time, all precautions to protect the healthcare personnel from viral transmission should be taken. In this review, we summarize the evidence supporting the application of HFNO and NIV in severe COVID-19 hypoxemic respiratory failure, analyse the risks associated with their use and provide a path for their proper implementation.

Reduction in Hospitalizations for Respiratory Diseases during the First COVID-19 Wave in Greece.

INTRODUCTION: During the first COVID-19 wave, a considerable decline in hospital admissions was observed worldwide. AIM: This retrospective cohort study aimed to assess if there were any changes in the number of patients hospitalized for respiratory diseases in Greece during the first CO-VID-19 wave. METHODS: In the present study, we evaluated respiratory disease hospitalization rates across 9 tertiary hospitals in Greece during the study period (March-April 2020) and the corresponding period of the 2 previous years (2018-2019) that served as the control periods. Demographic data and discharge diagnosis were documented for every patient. RESULTS: Of the 1,307 patients who were hospitalized during the study period, 444 (35.5%) were males with a mean (±SD) age of 66.1 ± 16.6 years. There was a 47 and 46% reduction in all-cause respiratory morbidity compared to the corresponding periods of 2018 and 2019, respectively. The mean incidence rate for respiratory diseases during the study period was 21.4 admissions per day, and this rate was significantly lower than the rate during the same period in 2018 (40.8 admissions per day; incidence rate ratio [IRR], 0.525; 95% confidence interval [CI], 0.491-0.562; p < 0.001) or the rate during 2019 (39.9 admissions per day; IRR, 0.537; 95% CI, 0.502-0.574; p < 0.001). The greatest reductions (%) in the number of daily admissions in 2020 were observed for sleep apnoea (87% vs. 2018 and 84% vs. 2019) followed by admissions for asthma (76% vs. 2018 and 79% vs. 2019) and chronic obstructive pulmonary disease (60% vs. 2018 and 51% vs. 2019), while the lowest reductions were detected in hospitalizations for pulmonary embolism (6% vs. 2018 and 23% vs. 2019) followed by tuberculosis (25% vs. both 2018 and 2019). DISCUSSION/CONCLUSION: The significant reduction in respiratory admissions in 2020 raises the reasonable question of whether some patients may have avoided seeking medical attention during the COVID-19 pandemic and suggests an urgent need for transformation of healthcare systems during the pandemic to offer appropriate management of respiratory diseases other than COVID-19.

Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece.

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID-designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86-171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.