COVID-19 Infection in Frailty — Still Plenty of Research Needed but Making Progress

Following the outbreak of the COVID-19 outbreak and its devastating impact, there came a rush for producing an effective and safe vaccine applicable across a wide range of susceptible people. Within a short space of time, frailty (along with advanced age) began to emerge as an important factor in the poor outcome of older people (1, 2). In fact, older residents of care homes (where frailty is common) were particularly suffering enormously from this pandemic with high rates of admission to hospital and associated high inpatient mortality and morbidity. It soon became clear that the whole epidemiology of COVID-19 incidence, severity of illness and mortality seem to be shifted towards older people particularly those with multiple comorbidities such as diabetes, hypertension, and cardiovascular disease (3).

Since then a large amount of work has taken place to elucidate the effects of frailty on vaccination status since earlier work showed that frailty was shown to be associated with poor post-vaccination immune response and increased rates of influenza like illness and laboratory-confirmed influenza infection (4). In a prospective cohort study in a tertiary hospital investigating older patients (aged ≥65 years) admitted with community acquired pneumonia, nursing home residency (a proxy for frailty) was an independent predictor of viral pneumonia (relative risk (RR) 3.06, P = 0.01) which also highlights the role of frailty in institutionalised populations for the increased risk of viral illness (5).

Two articles in this review, both originating in the same VA geriatric research center in Miami, USA, provide important perspectives to the continuing work in this area.

The first article by Tang et al. (6) describes a primary aim of the study is to compare vaccine effectiveness against COVID-19 infection according to frailty status and included U.S. veterans receiving care at Veterans Health Administration (VHA) medical centers, who had at least one COVID-19/flu like symptom and were tested for SARS-CoV-2 during the Delta wave in the US. Frailty assessment was by an operationalized frailty tool (validated VA Frailty Index) which was based on the deficit accumulation conceptual framework. Over 58,000 subjects were included and who consisted of being robust (47%), 28% were prefrail, and 25% frail. Either the Pfizer or Moderna vaccines were used. The results indicated that vaccine effectiveness against symptomatic infection was lower in patients with frailty compared to the robust and prefrail groups, and that the peak effectiveness of the vaccine was also delayed, The waning of vaccine effectiveness was also more pronounced in patients with frailty compared with the robust and prefrail groups.

In the article by Resendez et al. (7), the FI-LAB (based on laboratory values and early vital signs) was used primarily as an alternative prognostic marker for inpatient mortality in those with COVID-19. The mean age of the participants (n = 615) was lower than usual (mean age at 66 years) reflecting their admission via a Veteran’s administration process. High FI-LAB moderate to high FI-LAB scores were associated with higher inpatient mortality (>3-fold increase compared with lower group, p<0.00.1), and higher rates of prolonged hospitalisation (p<0.001). Overall, the FI-LAB represents an interesting but effective tool that enables hospitalbased clinicians to estimate and stratify risk for patients with frailty.

Studies of this kind are subject to all types of bias, heterogeneity of participants, and lack of standardisation of measures but ingenuity of design of workable and easily interpreted frailty assessment tools should also be welcomed. In one sense, this will bring frailty measurement in hospital to become routine as laboratory and clinical day to day management. Vaccination practices in older people should be alert to more scrutiny by Public Health departments of factors that decrease the effectiveness of known and future vaccines in an ageing population.

Quite clearly, safety issues, acceptability in older people, and cost-effectiveness of vaccines for other major infectious diseases that have a significant impact on outcomes must also be considered (1). In addition, there are ethical issues involved in striving to protect the ‘at risk’ older person with frailty involving a balance between containment (which results in social isolation and its sequelae) but offers a degree of protection from a viral threat versus dignity, personal choice and autonomy (8). Although we are not there yet in this approach, we can at least support the view that frailty should be considered in risk assessment models in all future clinical trials. This ensures vaccines have a favourable immune response in frail individuals, and in this respect, the input of geriatricians be welcomed for optimise trial design.

Conflict of interest: None.