COVID-19 in Older People: A Rapid Clinical Review

Fiona E. Lithander; Sandra Neumann; Emma Tenison; Katherine Lloyd; Tomas J. Welsh; Jonathan C. L. Rodrigues; Julian P. T. Higgins; Lily Scourfield; Hannah Christensen; Victoria J. Haunton; Emily J. Henderson

Disclosures

Age Ageing. 2020;49(4):501-515.

Clinical Overview of COVID-19

The current WHO suspected case definition is shown in Box 1.^[5] Clinical manifestations are summarised in Box 2. Cohort studies of patients with mild and moderate disease showed that fever was the most common symptom in 82–87% of cases, followed by cough in 36–66%.^[13] This reflects findings from a meta-analysis of cases in China^[6] where, of note, fever was more common during admission than at presentation.^[14] In the RADAR COVID-19 study, in patients in a community setting with symptoms that warranted testing, anosmia was present in 59% who tested positive.^[9] Other clinical features include headache, rhinorrhoea, gastrointestinal symptoms, sore throat and fatigue. Cardiac complications are described, including myocarditis,^[15] pericardial effusion on imaging^[16] and arrhythmia,^[17] which are seen more commonly in those with greater disease severity.^[18] Patients with severe infection can develop a pro-inflammatory cytokine release syndrome, which can lead to rapid deterioration and death.^[19] The majority of studies to date have notably reported symptoms occurring in patients with proven infection in hospitals.

Early reports substantiate that older people with COVID-19 will likely present atypically;^[20] experience in France suggests that this group may initially present with delirium, postural instability or diarrhoea, rather than with typical respiratory symptoms and fever.^[21] With COVID-19 being detected in older people who are in hospital for other illnesses, such as following a fall,^[21] it remains to be determined as to what extent these index events are precipitated by COVID-19 infection versus COVID-19 being found incidentally. Atypical presentations omitted from public health campaigns, such as diarrhoea, showed a pooled incidence rate of 9.2%.^[7] Limited data are available on rates of delirium in COVID-19 infection, although the risk has been identified by the WHO and the British Geriatrics Society (BGS) who have produced specific guidelines to support delirium management in this context (Box 3).^[23]

Typical findings on blood tests are lymphopenia and elevated C-reactive protein (CRP).^[10] In moderate-to-severe cases, increased procalcitonin levels have been observed.^[24] Consistent with the aforementioned cardiac complications, severe cases often see raised levels of troponin I, D-dimer and lactate dehydrogenase.^[3,10,17,25] Chest radiograph (CXR) features are 'foci' of ill-defined 'opacification' with bibasal predilection, evolving to consolidation.^[7,10] On chest computed tomography (CT), typical chest findings include lower lobe and peripheral predominance with multiple, bilateral foci of ground glass opacity^[6,7,12] with or without crazy paving, peripheral consolidation, air bronchograms and reverse halo or perilobular pattern.^[26] Importantly, radiological changes may be absent in early disease (56% of 36 patients scanned between 0 and 2 days of symptom onset had a normal CT)^[11] and minimal in mild disease (18% of 877 patients with non-severe disease clinically had no radiological abnormality). In severe cases, only 3% had no radiological signs. In light of this, COVID-19 cannot necessarily be ruled out on the basis of a normal CT while there is some evidence to suggest that the negative predictive value of CT is higher when symptom duration is >1 week.^[26–28]

The main complication of COVID-19 is acute respiratory distress syndrome (ARDS). This is reported to occur in between 15%^[6] and 23%^[7] of cases. Other complications include respiratory failure,^[29] acute kidney injury^[29,30] and liver dysfunction.^[30] Described causes of death include pneumonia, multi-organ failure and severe acute respiratory syndrome.^[3,10]

There is a striking paucity of peer-reviewed evidence that examines the specific characteristics of COVID-19 in older people. Nonetheless, guidance relating to the care of older people is emerging from the international community. This guidance spans ethical considerations to the clinical management of COVID-19 in different settings^[31] with a holistic assessment in their guidance on critical care in patients aged over 65 years. The French Society of Geriatrics and Gerontology (SFGG) has highlighted the non-specific presentation of COVID-19 illness in older people. A joint consensus has been collated between the British Geriatrics Society, European Delirium Association and the Faculty of Old Age Psychiatry at the Royal College of Psychiatrists on managing delirium in suspected and confirmed cases.^[23] Specific guidelines from the United States have been published for emergency department providers^[32] usefully outlining that immunosuppression in older adults, and or the presence of comorbidities, should prompt a lower threshold for COVID-19 testing. In addition, this guidance highlights the additional challenge of communicating with people with cognitive and sensory impairments while personal protective equipment is being worn.

1 2 3 4 5 6 7 8 9 10 11

Next Section

Table 1. Prognostic Studies – Study characteristics and outcomes
Reference	Sample size	Population	Hospital	Admissions	Outcome
Fu et al. [77]	200	Hospital admissions confirmed by real-time RTPCR assay for SARS-CoV-2 RNA	Union Hospital of Huazhong University of Science and Technology, Wuhan, China	1 January–30 January 2020	Mortality
Gao et al. [2]	54	Hospital admissions with laboratory (RT-PCR) confirmed SARS-Cov-2 infection; CT of the lung conformed to the manifestation of viral pneumonia	Hubei General Hospital, Chongqing, China	Not available	Mortality
Liu et al. [1]	78	Hospital admissions with positive test result for COVID-19 nucleic acids by real-time fluorescence RT-PCR hospitalised for >2 weeks, died while hospitalised, or had recovered and been discharged	(1) The Central Hospital of Wuhan, (2) Tongji Hospital, (3) Wuhan Pulmonary Hospital, Wuhan, China	30 December 2019–15 January 2020	Disease progression to severe, critical or death
Zhou et al. [3]	191	Hospital admissions diagnosed with COVID-19 according to WHO interim guidance	Jinyintan Hospital and Wuhan Pulmonary Hospital, Wuhan, China	29 December 2019–31 January 2020	Mortality
Chen et al. [78]	249	Hospital admission diagnosed according to Chinese National Guideline for COVID-19 diagnosis and treatment, as well as the World Health Organisation interim guidance	Shanghai Public Health Clinical Center (SPHCC), Shanghai, China	20 January–6 February 2020	ICU admission
Guan et al. [79]	1590	High-throughput sequencing or real-time RT-PCR assay findings for nasal and pharyngeal swab specimens were positive	575 Hospitals across China, nationwide	21 November 2019–31 January 2020	ICU admission, or invasive ventilation or death
Liu et al. [80]	64	Medical staff following admission to isolation wards with RT-PCR positive nCoV-19 positive cf. WHO interim guidance	Wuhan Union Hospital, Wuhan, China	16 January–15 February 2020	Hospital discharge
Cai et al. [81]	298	Hospital admissions confirmed according to WHO interim guidance (RT-PCR)	Third people's Hospital of Shenzhen, Guangdong, China	11 January–6 February 2020	Duration of positive viral test results. Virus clearance defined as 2 negative qPCR detection results at an interval of 24 h
Cheng et al. [82]	701 (of which 442 included in prognostic analysis)	Hospital admissions COVID-19 positive according to the guidance provided by the Chinese National Health Commission: ≥2 clinical diagnosis criteria and a positive result to high-throughput sequencing or RT-PCR assay. Patients with a history of maintenance dialysis or renal transplantation were also excluded	Tongji Hospital, Wuhan, China	28 January−11 February 2020	Mortality association between kidney disease and in-hospital death
Yang et al. [83]	55	Hospital admission with SARS-CoV-2 confirmed by qRT-PCR or sequencing	Fifth Medical Center of PLA General Hospital, Beijing, China	27 December 2019–18 February 2020	Disease progression
Liu et al. [84]	41	Staff of the central hospital of Wuhan admitted with COVID-19 confirmed by RT-PCR	Central Hospital of Wuhan, Wuhan, China	15 Jan–24 Jan 2020	In-hospital adverse events (defined as respiratory failure or ARDS, transfer to ICU, invasive mechanic ventilation, acute cardiac injury, acute kidney injury, acute hepatic injury, acute myocyte injury, shock, secondary infection and death)
Bai et al. [85]	199	Hospital admission with positive viral nucleic acid test result on throat swab samples (n = 80) or clinical parameters (n = 53)	Wuhan Pulmonary Hospital, Wuhan, China	3 January–13 February 2020	Progression of disease severity (using machine learning; results not in Appendix A2, Supplementary data are available in Age and Ageing online)
Yan et al. [86]	404	Hospital admissions with SARS-CoV-2 nucleic acid positive by RT-PCR; or virus sequence detected share high homology with the known sequence of SARS-CoV2 in respiratory or blood samples	Tongji Hospital, Wuhan, China	10 January–18 February 2020	Critical illness (using machine learning with supervised XGBoost classifier, results not in Appendix A2)

Box 1. World Health Organisation suspected case definition ([5]).
A suspected case is A. A patient with acute respiratory illness (i.e. fever and at least one sign or symptom of respiratory disease, e.g. cough or shortness of breath) AND with no other aetiology that fully explains the clinical presentation AND a history of travel to or residence in a country, area or territory that has reported local transmission of COVID-19 disease during the 14 days prior to symptom onset. OR B. A patient with any acute respiratory illness AND who has been a contact of a confirmed or probable case of COVID-19 disease during the 14 days prior to the onset of symptoms (see the definition of contact below). OR C. A patient with severe acute respiratory infection (i.e. fever and at least one sign or symptom of respiratory disease, e.g. cough or shortness breath) AND who requires hospitalisation AND who has no other aetiology that fully explains the clinical presentation.

Box 2. Clinical overview of COVID-19.
Clinical manifestations • Fever [6] • Dry Cough [6] • Dyspnoea • Myalgia • Fatigue • Diarrhoea [7] • Asymptomatic [8] • Acute respiratory distress syndrome [6,7] • Atypical presentations (e.g. behavioural change, balance problems, falls), particularly in older adults • Anosmia [9] Typical biochemical findings (not exhaustive) [7,10] • Lymphopenia • Elevated CRP Radiological findings [11] • CXR [12] – Bilateral, ground glass opacification which is ill-defined and more commonly seen in the periphery and the right lower lobe • CT Chest – Can be normal in the early stages of disease, but a normal CT after a week suggests COVID-19 much less likely – Lower lobe predominant, peripheral predominant, multiple, bilateral foci of ground glass opacity – ±Crazy paving, peripheral consolidation, air bronchograms, reverse halo/perilobular pattern Causes of death [3,10] • Pneumonia • Sepsis (viral or bacterial) • Severe acute respiratory syndrome

Box 3. Useful resources.
World Health Organization Case management: outlines the management of people with COVID-19 infection in secondary care https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management European Geriatric Medicine Society EuGMS Task Force on COVID-19 collates topics on care of older people during the coronavirus pandemic from across Europe https://www.eugms.org/news/read/article/490.html The National Institute for Health and Care Excellence UK Rapid guidelines and evidence reviews including critical care, patients on dialysis, risk of angiotensin converting enzyme (ACE) inhibitors and non-steroidal anti-inflammatory drugs (NSAIDS) https://www.nice.org.uk/covid-19 UK Government Advice on people in residential care and supported living https://www.gov.uk/government/publications/covid-19-residential-care-supported-living-and-home-care-guidance Ethical framework for planning adult social care during the coronavirus outbreak https://www.gov.uk/government/publications/covid-19-ethical-framework-for-adult-social-care British Geriatrics Society COVID-19: managing the COVID-19 pandemic in care homes: good practice guide [22] https://www.bgs.org.uk/resources/covid-19-managing-the-covid-19-pandemic-in-care-homes Coronavirus: managing delirium in confirmed and suspected cases [23] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases British Society of Thoracic Imaging COVID-19 guidance for the reporting radiologist https://www.bsti.org.uk/standards-clinical-guidelines/clinical-guidelines/bsti-covid-19-guidance-for-the-reporting-radiologist/

Box 4. Suggested future research directions.
Testing Identification of the diagnostic accuracy, indication and optimal method(s) for testing in older people in the presence and absence of symptoms and in different settings, e.g. primary versus secondary care, residential and nursing homes. Clinical presentation Evaluation of the extent to which frailty, comorbidity and age and specific drugs (e.g. ACE inhibitors, NSAIDs and others, e.g. immunosuppressants) influence the clinical presentation and disease trajectory of COVID-19 in older people. Ascertainment of the longer term morbidity with evaluation of physical, cognitive and psychosocial outcomes. Treatment and rehabilitation Ongoing monitoring and advocacy to ensure that randomised clinical trials recruit older adults and that their enrolment is facilitated. Rapid implementation and evaluation of established and novel rehabilitation strategies are required to support post-acute care of older patients with COVID-19 infection. Evaluation of the advanced care planning discussion, documentation and communication along with optimal treatment strategies at the end of life. Wider impact Ascertainment of the impact of public health measures, particularly social isolation, on older people is warranted to determine the relative risks versus benefit of these strategies. Evaluation of multidisciplinary working across organisations to optimise acute care and rehabilitation.