Association of Frailty With Mortality in Older Inpatients With Covid-19

A Cohort Study

Darren Aw; Lauren Woodrow; Giulia Ogliari; Rowan Harwood

Disclosures

Age Ageing. 2020;49(6):915-922. 

In This Article

Discussion

In our cohort of older adults aged 65 years and older, admitted to a secondary care hospital with COVID-19, worsening frailty on admission was associated with an increased risk of all-cause mortality. This association was independent of age, sex, ethnicity, deprivation, previous admission to hospital and clinical severity on admission. We confirmed that age and male sex were associated with an increased risk of mortality.

Context

Increasing age has previously been associated with COVID-19 mortality. Our study shows an association between frailty and mortality in older adults with COVID-19. It is in line with prior literature, showing an association between frailty and non-COVID mortality in older adults in the community as well as among older adults admitted to hospital.[16–19] It is also in line with a previous report showing that frailty may negatively affect recovery from another viral illness, influenza, and its associated acute respiratory illness in older adults.[20]

In our study, the association between frailty and clinical severity on admission, as measured by NEWS-2 score, was non-significant and the effect size very small (Spearman's rho 0.071).[21] This is contrary to previous studies, showing positive although weak associations between frailty and clinical severity on admission to acute hospital settings in the UK (Spearman's rho 0.17 and 0.23, respectively).[16,22] These studies have suggested that CFS scoring in the acute hospital may inadvertently incorporate acuity into the scoring, rather than measuring baseline frailty in the 2 weeks prior to admission. Given that no association between frailty and clinical severity on admission was found in our cohort of patients with COVID, we think that this is unlikely to have occurred in our study. Previous reports suggested that frail patients may present later to the hospital, with high acute illness severity, after failed attempts to manage them in the community.[16,23] However, there may be a prompt referral to the hospital of frail patients with suspected COVID infection, for fear of contagion in the community. Furthermore, we speculate that the clinical acuity of patients with COVID may be unrelated to frailty, contrary to that of other infectious illnesses, as immune reaction responses may differ.

Of note, in our study, older adults who were classified as vulnerable or mildly frail did not have an increased mortality risk, compared to the fittest. Our numbers were insufficient to make very precise estimates of mortality for each individual CFS grade, although a broad dichotomy (CFS 1–5 versus 6–9) was suggested, and increase in mortality risk was noted only for those adults with moderate or severe frailty, compared to the fittest. It could be that our study was underpowered to detect differences in mortality risk between these groups. As an alternative explanation, vulnerable and mildly frail older adults may have a mortality risk similar to that of the fittest, in the context of the COVID-19 pandemic.

Furthermore, our findings remained consistent when using different diagnostic criteria for COVID-19. First, we showed the association between frailty and mortality, in the whole cohort of patients, where diagnosis of COVID-19 could be reached by positive RT-PCR, radiological criteria or clinical criteria. We initially included the whole cohort of patients not to miss any cases of COVID-19, as the sensitivity of RT-PCR could be as low as 60–70%.[24] Later, when excluding patients with only radiological or clinical criteria but a negative RT-PCR, who could have been misclassified as COVID-19, our findings remained unchanged.

We selected all-cause mortality as our main outcome. Clinical determination of the cause of death is frequently inaccurate in older adults.[25] All-cause mortality is the most robust outcome but may include non-COVID deaths. Moreover, COVID-19 may have contributed to a clinical decline—possibly through hospitalisation—also in those patients who were not certified as deceased for COVID-19. Furthermore, when we performed the analyses on the association between frailty and only COVID-19 certified mortality, we found similar findings.

Strengths and Limitations

The strengths of our study are the longitudinal design, the large sample size and the use of an internationally validated scale to define frailty. Although there is no universal definition of frailty, many scales have been proposed to measure it.[26] CFS is described by brief descriptions and pictograms, largely describing functional activity (disability) states. It thus only approximates to the theoretical construct of frailty; however, it has the advantages of being brief, practical, and widely used in clinical practice. It should be based on premorbid function 2 weeks prior to admission, for this to have validity and uniformity in the assessment. However, CFS scoring could be subjective and the degree of frailty may have been misinterpreted as a consequence of presenting illness acuity.

Our study was based in a single centre. We did not include frail older adults, on a palliative trajectory prior to COVID-19, who may have received palliative care in the community without being admitted to hospital. The findings of our study may thus not be generalisable to these older adults. Every effort was made to follow-up the patients for mortality, but we may not have ascertained all those who died after leaving the hospital, or whether their death was attributed to COVID-19. As our main focus was on all-cause mortality, this is likely to be a minor limitation. We had to estimate CFS from clinical records where these had not been recorded electronically, and data were incomplete for 13 patients.

Implications for Practice

Our data may inform discussion on prognosis in the clinical setting, and this information may be useful for discussions with families, and may also indicate a group in whom 'twin-tract' active and palliative management may be appropriate and should be considered.

Our findings could also be useful in case-mix adjustment for governance purposes.

There has been much debate about defining ceilings of care for older patients with COVID-19 disease. Some guidance suggests that patients with a CFS score of 5 or more would be unlikely to benefit from ITU care.[27,28] As our patient group was managed predominantly on standard medical wards, rather than critical care, we do not feel able to give recommendations on ITU allocation. However, we highlight that about half of our patients with moderate to severe frailty survived the hospital admission due to COVID-19.

This adds to the argument that frailty alone should not be used in determining active medical treatment.[29]

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