ABSTRACT
BACKGROUND: The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. METHODS: Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. DISCUSSION: Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.
ABSTRACT
IMPORTANCE: Among COVID-19 cases, especially the (frail) elderly show a high number of severe infections, hospital admissions, complications, and death. The highest mortality is found between 80 and 89 years old. Why do these patients have a higher risk of severe COVID-19? In this narrative review we address potential mechanisms regarding viral transmission, physical reserve and the immune system, increasing the severity of this infection in elderly patients. OBSERVATIONS: First, the spread of COVID-19 may be enhanced in elderly patients. Viral shedding may be increased, and early identification may be complicated due to atypical disease presentation and limited testing capacity. Applying hygiene and quarantine measures, especially in patients with cognitive disorders including dementia, can be challenging. Additionally, elderly patients have a decreased cardiorespiratory reserve and are more likely to have co-morbidity including atherosclerosis, rendering them more susceptible to complications. The aging innate and adaptive immune system is weakened, while there is a pro-inflammatory tendency. The effects of SARS-CoV-2 on the immune system on cytokine production and T-cells, further seem to aggravate this pro-inflammatory tendency, especially in patients with cardiovascular comorbidity, increasing disease severity. CONCLUSIONS AND RELEVANCE: The combination of all factors mentioned above contribute to the disease severity of COVID-19 in the older patient. While larger studies of COVID-19 in elderly patients are needed, understanding the factors increasing disease severity may improve care and preventative measures to protect the elderly patient at risk for (severe) COVID-19 in the future.