SARS-CoV-2 was more likely to affect older patients, particularly those with comorbidities . To our best knowledge, this is the first report to systematically describe the extrapulmonary organ damage caused by SARS-CoV-2 in older patients. In this study, we showed that older patients with COVID-19 exhibited more coexisting diseases, ARDS and extrapulmonary organ damage, which were associated with a higher mortality. Moreover, oldest-old patients showed higher incidence of multi-organ dysfunction and mortality.
Aging is a complex and multifactorial process. Frailty, the common problem of aging population, is a nonspecific state of vulnerability to poor resolution of homeostasis following a stress . The prevalence of frailty increased with age, the elderly older than age 65 accounted for 22.4%, while 43.7% for those over 85 years old . Increasing frailty with age was associated with increased risk of infection and mortality . In this study, 41.7% of patients were aged over 65 years and 3.2% was 85 or even older. In addition, many older patients with COVID-19 had one or more comorbities, making them more susceptible to SARS-CoV-2 infection and had greater severe illness. In this study, 72.3% of older patients had at least one coexisting illness.
Compared with SARS, COVID-19 had a lower case fatality. It has been reported that the over-all mortality was 1.4% . Although most younger people infected by SARS-CoV-2 were asymptomatic or mildly ill, the elderly exhibited more severe symptoms and higher mortality. It is estimated that the mortality was 1.4% in the elderly less than 60 years old while increased by 4.5% in older individuals over 60 years old and by 14.8% in patients aged 80 or older . In this study, the condition of the elderly was more serious and the mortality was 18.6%, which was significantly higher than that of young and middle-aged patients.
SARS-CoV-2 infection is able to result in clusters of severe pneumonia and even ARDS, which is the leading cause of death in patients with COVID-19. In one study enrolling 201 COVID-19 patients, 41.8% of patients developed ARDS and 52.4% of them died eventually . In another study by Lian J et al, 16.9% of older patients (≥60 years) developed ARDS, which only accounted for 5.37% in younger patients (<60 years) . They argued that older age was associated with greater risk of development of ARDS and death . In this study, older patients exhibited higher counts of neutrophils and CRP levels, suggesting an augmented inflammatory response. Meanwhile, older patients showed a higher incidence of ARDS, which was an independent risk factor for death.
Some COVID-19 patients without common symptom (fever or cough) came to hospital with only cardiovascular manifestations as their presenting symptoms. Cardiac injury is also one of essential causes of death in patients with COVID-19. Patients with cardiovascular comorbidities were more likely to develop cardiac complications and Ruan et al. reported that 40% of deaths were associated with circulatory failure due to cardiac injury . In this study, older patients had increased incidence of acute cardiac injury and heart failure, which were independently associated with poor outcome in elderly patients with COVID-19. Importantly, acute cardiac injury could be developed no matter whether there was cardiovascular disease previously.
Nutritional status of the host exerts a crucial role in the defense against infection, and individuals with nutritional deficiency are more susceptible to a series of infectious diseases which can lead to a detrimental consequence [16,17]. Malnutrition has been considered as an independent risk factor for increased complications and higher mortality in hospitalized patients . The basic nutritional status of older patients with chronic diseases is always poor, which makes them tend to be critically ill after infection . In this study, the older patients were more likely to develop hypoalbuminemia and decreased hemoglobin, suggesting they were under a poor nutrition state, which might be a cause of higher mortality in older patients.
Recently, a descriptive study indicated 36.4% of patients with COVID-19 had nervous system manifestations . However, we did not find any difference of nervous system manifestations among the three groups. And, we also did not find any difference of acute liver or kidney injury. However, oldest-old patients showed higher skeletal muscle injury and acute kidney injury.
Immune system exerts a central role in host-viral interactions and aging has the ability to induce a series change that affects the immune system. Immunosenescence is an age-related process that affects both innate and adaptive immunity, increasing the vulnerability and mortality of elderly to infectious diseases . Immune organs such as thymus and lymph nodes atrophy gradually with age, and aging has a profound impact on the phenotype and functions of various immune cells [21,22]. Many patients with COVID-19 exhibited lymphopenia, which was more prominent in those severe patients [11,23]. In our study, persistent and more severe lymphopenia was observed in older patients, 32.9% of whom had lymphocyte counts below 0.8×109/L, which suggested a damaged immune system. The damaged immune function, caused by immunosenescence and preceding coronavirus infection, increased the susceptibility to secondary bacterial pneumonia.
To date, no vaccine or specific therapeutic drug for COVID-19 has been approved. The treatment of elderly patients faces special challenges due to complications and general age-related vulnerability. Although glucocorticoids treatment was likely required in patients with coronavirus pneumonia, their efficacy remains controversial. A meta-analysis enrolled 5270 patients showed that corticosteroid use may increase mortality and serious adverse reactions in patients with COVID-19 . However, in RECOVERY trial, dexamethasone (6mg once daily for up to 10 days) treatment reduced 28-day mortality among those COVID-19 patients receiving invasive mechanical ventilation or oxygen at randomization but not among patients receiving no respiratory support . Among 2104 patients, 54% of patients with dexamethasone therapy were younger than 70 years . Older patients always have more comorbidities and they are not sensitive to many drugs and have more adverse effects of prescription drugs than younger patients. Therefore, glucocorticoids use may present a different effect in older patients with COVID-19. In our study, we focused on the effect of glucocorticoids in the older patients with COVID-19 and found glucocorticoids use were associated with an increased mortality in older patients. Maybe the different results were due to the heterogeneity in the choice, dosage and timing of steroids therapy, different crowds, medical conditions and disease severity. Therefore, caution in glucocorticoids use in older patients is advisable.
There were several limitations in this study. First of all, this was a single-center, retrospective analysis and a number of confounding factors may influence the clinical outcomes. Secondly, as one of the designated hospitals for severe COVID-19, most of patients enrolled were severe cases, which might be different from the whole infected population.