Clinical characteristics study of elderly patients aged 75 or older with COVID-19 pneumonia in China

Background: Coronavirus disease 2019 (COVID-19), a newly emerged respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become pandemic. Clinical observation indicated that elderly patients had high incidence of severe pneumonia and poor treatment ecacy. Therefore, this study was to clarify the characteristics of elderly patients aged 75 or older with COVID-19 pneumonia in order to guide rational treatment for elderly patients. Methods: we enrolled 331 elderly patients aged 75 or older with conrmed COVID-19 in Huoshenshan hospital of Wuhan from February 3rd to March 31st. The cases were divided into general, serious and critical groups according to severity after hospitalization, and the difference among groups were compared by R package statistics software. Results: Compared with general group, serious and critical groups had more underlying comorbidities and higher incidence of cough, breath shortness and anorexia. Moreover, there existed obviously differences in many of laboratory indexes and CT images among them. serious and critical elderly patients were more likely to receive oxygen, mechanical ventilation, expectorant, corticosteroid, abidor, cephaloprin, imipenem, human serum albumin (HSA), nutrition support, anti SARS-CoV-2 positive plasma and actemra. Multivariate analysis of factors showed that male sex, hypertension, diabetes, renal diseases, breath shortness, neutrophil, platelet, creatinine, lactate dehydrogenase were the risk factor for serious and critical illness. While blood cell (WBC) was the protective factor. Conclusion: elderly patients have high incidence of severe pneumonia and poor treatment ecacy. The reasons might be that many of the elderly patients with COVID-19 pneumonia have certain chronic disease, poor immune function and a meager response to the virus. the pathogenic mechanism of SARS-CoV-2 might be involved in the cell-mediated immunity and cytokine storms by acting on lymphocytes.


Introduction
Coronavirus disease 2019 (COVID-19), a newly emerged respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become pandemic [1]. This causative coronavirus was con rmed to be a distinct clade from the coronavirus that are enveloped, positive-sense, single-stranded RNA viruses with nucleocapsid of helical symmetry, which had widely been known to cause respiratory infection in humans after outbreak the "Sever Acute Respiratory Syndrome (SARS)" and "Middle East Respiratory Syndrome (MERS)" [2]. Although the mechanisms associated with the infectiousness of SARS-CoV-2 is not clear, Structural analysis suggests it is likely entering human cells through the ACE2 receptor and may be transmitted to human from the market where wild animals were sold out. According to the previous reports the SARS-CoV-2 are thought to have originated in bats [3,4]. the epidemiological data demonstrated person-to-person transmission by droplet respiratory, touch and otherwise.
Clinical characteristics associated with patients infected with SARS-CoV-2 range from mild respiratory illness to serious acute respiratory disease. Pneumonia appears to be the most frequent manifestation of SARS-CoV-2 infection, characterized primarily by fever, cough, fatigue and breath shortness. Generally, it is thought that the period from infection to appearance of symptoms varies was 14 days, the onset of fever and respiratory symptoms occurred approximately three to six days after presumptive exposure [5,6]. Although numerous compounds had been proven effective against virus, there was no obvious effect on newly emerged SARS-CoV-2. The main therapeutic strategy focused on symptomatic support [2].
Our clinical observation indicated that elderly patients have high incidence of severe pneumonia, acute respiratory distress syndrome (ARDS), even multiple organ failure than other patients, and showed poor treatment e cacy after hospitalization. However, large-scale analyses of clinical characteristics of elderly patients had been scarce. In this study, we aimed to clarify the characteristics of elderly patients aged 75 or older with COVID-19 in order to guide rational treatment for elder patients.

Study design and participant
This study was a retrospective cohort study of Wuhan Huoshenshan hospital and approved by the ethics committee of Wuhan Huoshenshan Hospital (No. HSSLL024). All elderly patients aged 75 or older (331 cases) with con rmed COVID-19 admitted to Huoshenshan Hospital of Wuhan from February 3rd to March 31st were enrolled, which occupied almost 1/10 of total number of patients in Huoshenshan hospital. Written or oral informed consent was obtained from these elderly patients. De nitions COVID-19 was con rmed by detecting SARS-CoV-2 RNA in throat or/and nasal swab samples using a virus nucleic acid detection kit according to the manufacturer's protocol (Luoyang Eisen Biotechnology Co.,Ltd) in class III bio-safety lab of Huoshenshan hospital. Depending on illness severity, the elderly patient with COVID-19 pneumonia were grouped as general, serious and critical group [7]. serious group was de ned if satisfying at least one of the following items:1) breathing rate ≥ 30/min; 2) pulse oximeter oxygen saturation (SpO2) ≤ 93%; 3) ration of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≤ 300 mmHg. Critical group was de ned if satisfying at least one of the following items: 1) respiratory failure occurred and received mechanical ventilation; 2) shock; 3) combined with failure of other organs and received care in the intensive care unit (ICU). Otherwise, it was classi ed as general group. ( Figure.1 showed the chest-image dynamics of general and serious COVID-19). The criteria for evaluating rehabilitation of COVID-19 patient were 1) two consecutive test of SARS-CoV-2 RNA in throat swab samples was negative; 2) obvious alleviation of respiratory symptoms (e.g. cough, fatigue and breath shortness) ; 3) maintenance of normal body temperature for ≥ 3 days without the use of corticosteroid or antipyretics; 4) improvement in radiological abnormalities by chest CT detection [7].

Data collection
A COVID-19 case report form was designed to document primary data. The following information was extracted from all elderly patient (aged 75 or older): age, gender, medical history, symptoms, severity assessment, laboratory ndings, chest CT ndings and treatment from electronic medical records.

Statistical analysis
Categorical data were described as percentages, and continuous data were described as median with interquartile range (IQR). Nonparametric comparative test for continuous data and X 2 test for categorical data were used to compare variables among groups. P < 0.05 was considered statistically signi cant. The variables identi ed by univariate analysis (p < 0.05) were put into the multivariate analysis, in which these variables were adjusted by disease severity. All statistical analyses were performed using R package statistics software.

Discussion
Since the outbreak of COVID-19, the number of patients had increased dramatically in the word. It had been reported that COVID-19 exhibit mild to moderate symptoms, but approximately 15% progress to severe pneumonia and about 5% eventually develop ARDS, septic shock and/or multiple organ failure [1]. Especially, Elderly patients had a signi cantly higher prevalence of severe pneumonia, who had an exacerbation in clinical symptoms, laboratory ndings and CT images [7]. Therefore, clinicians should assess the severity of illness timely and provide interventions for elder patients with COVID-19 pneumonia, which was conductive to shorten the course of disease, prevent disease progression and reduce mortality.
In this study, 331 elderly patients with COVID-19 pneumonia were divided into general, serious and critical groups according to the severity of illness. it could be seen that 254 (76.7%) of elderly patients have certain chronic diseases and were worse than others. This was why elderly patients have high incidence of severe pneumonia and poor treatment e cacy. COVID-19 was like SARS and MERS in some clinical manifestations. In COVID-19 patients, fever, cough and breath shortness were most common symptoms, followed by fatigue and myalgia. However, neurological symptoms (e.g. headache and dizziness), gastrointestinal symptoms (e.g. Diarrhea, abdominal pain, nausea, vomiting) and upper respiratory tract symptoms (eg. nasal congestion, nasal discharge and sore throat) were relatively rare. Fever occurred in 98 100% of SARS or MERS patients, compared to 62.5% elderly patients with COVID-19 pneumonia in this study [8]. this result suggested that elderly patients may be have poor immune function and a meager response to the SARS-CoV-2. This was another reason why elderly patient have high incidence of severe pneumonia and poor treatment e cacy. It was worth noting that 37.5% of elderly patients presented no fever, suggesting that the absence of fever could not rule out the possibility of COVID-19. if fever was used to trigger detection for COVID-19, a substantial number of elderly patients without fever might be missed.
In radiological image ndings, 222 (67.1%) elderly patients had abnormal chest CT ndings. The lung lesions were mainly manifested as ground glass-like shadows and patchy shadows on CT image. Serious and critical groups had a higher proportion of pulmonary infection than general group, suggesting a more obvious in ammatory response in the lung. These results indicated that SARS-CoV-2 mainly destroyed and impaired the alveolar epithelial cells. In laboratory ndings, there existed obviously differences in the number of WBC, neutrophil, lymphocyte and platelet, serious and critical groups had lymphopenia, and the proportion of T lymphocyte subgroups (including CD3 + T cell, CD3 + CD4 + Th cell, CD3 + CD8 + CTL) signi cantly lower in serious and critical groups than that of general group. Meanwhile, the levels of ALT, AST, creatine, and CK in blood signi cantly increased in serious and critical groups. It was known that ALT and AST were important indicators of liver function, creatine was a kind of intelligent indicator of renal function and CK was a sensitive indicator of heat function. The increase of these indicators might be associated with some chronic diseases or/and irrational use of drug in these elderly patients. In additional, LDH, CRP and IL-6 were statistically signi cantly higher in serious and critical groups, LDH was an in ammatory predictor in many pulmonary diseases, such as obstructive disease, microbial pulmonary disease and interstitial pulmonary disease [7]. CRP as a widely used biochemical marker for in ammation, re ecting the acute sever systemic in ammatory response caused by viral infection. IL-6 is one of the irreplaceable cytokines in the in ammatory response and may play a key role in pathogenesis and progress of pulmonary caused by the virus. These indicated that SARS-CoV-2 might mainly act on lymphocytes, including CD3 + T cell, CD3 + CD4 + Th cell, CD3 + CD8 + CTL, and involve in the cell-mediated immunity and cytokine storms. But the exact mechanism needs to investigate further.
So far, there was no safe and effective treatment for COVID-19 in clinical application, because of poor e cacy and/or adverse reaction. Most patients recovered despite receiving antiviral, immunity enhancement and anti-in ammatory treatment, but it was more due to the supportive care with oxygen, nutrition support as needed, intensive care management. In present study, serious and critical elderly patients were more likely to receive oxygen therapy, ventilator support, corticosteroid, antivirals, antibacterial, immune enhancer and anti-in ammatory treatment, indicating these elderly patients may be have more severe state, more complication and worse prognosis, which seem to be causing a delay of the clinical course, even death.
In conclusion, more than 50% COVID-19 elderly patients were serious or critical illness, indicating elderly patients have high incidence of severe pneumonia and poor treatment e cacy. The reasons might be that many of the elderly patients have certain chronic disease, poor immune function and a meager response to the virus. the pathogenic mechanism of SARS-CoV-2 might be involved in the cell-mediated immunity and cytokine storms by acting on lymphocytes, but the exact mechanism needs to investigate further.

Declarations
Ethics approval and consent to participate This study was a retrospective cohort study of Wuhan Huoshenshan hospital and approved by the ethics committee of Wuhan Huoshenshan Hospital (No. HSSLL024).

Consent for publication
All authors reached an agreement to publish the study in this journal Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information les.
Competing interests