Recommendations for the prevention and treatment of the novel coronavirus pneumonia in the elderly in China

Abstract The population is commonly susceptible to the 2019 novel coronavirus (2019‐nCoV), especially the elderly with comorbidities. Elderly patients infected with 2019‐nCoV tend to have higher rates of severe illness and mortality. Immunosenescence is an important cause of severe novel coronavirus pneumonia (NCP) in the elderly. Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations, and pulmonary imaging, deserving particular attention. The general condition of the elderly should be considered during diagnosis and treatment. In addition to routine care and measures—such as oxygen therapy, antiviral therapy, and respiratory support—treatment of underlying disease, nutritional support, sputum expectoration complication prevention, and psychological support should also be considered for elderly patients. Based on a literature review and expert panel discussion, we drafted the "Recommendations for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly in China," aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.


| INTRODUC TI ON
In December 2019, there was an outbreak of novel coronavirus pneumonia (NCP) in Wuhan; the pathogen was 2019 novel coronavirus (2019-nCoV), which had not previously been detected in the human body. The World Health Organization (WHO) officially named the disease "coronavirus disease 2019 (COVID- 19)." Meanwhile, the International Committee on Taxonomy of Viruses named the novel coronavirus "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." Due to the measures of preventive control and medical treatment, the rising momentum of the epidemic in China has been contained and the epidemic has been alleviated. However, morbidity abroad is on the rise and the virus is spreading globally. According to data from the currently released report, the pathogen may infect people of all ages, but the severe disease rate is higher among the elderly population, which accounts for the vast majority of mortalities. [1][2][3] To curb the outbreak of novel coronavirus and reduce the harm to the elderly, we have compiled the "Key Points for the Prevention and Treatment of Novel Coronavirus Pneumonia in the Elderly (trial implementation)" in accordance with the recent literature.

| E TI OLOG I C AL FE ATURE S OF NOVEL CORONAVIRUS
On January 24, 2020, the Chinese Center for Disease Control the equivalent rates for SARS-CoV and MERS-CoV are 79% and 50%, respectively. 4 An essential receptor for SARS-CoV is angiotensin-converting enzyme 2 (ACE2) and this mainly results in the infection of cilia bronchial epithelial cells and type II alveolar epithelial cells. Studies 4,5 show that novel coronavirus is highly homologous to SARS-CoV, which can be attributed to the combination of virus spike protein and human ACE2 receptor protein militated to the host. This receptor is mainly distributed in the pulmonary vascular endothelial cells, heart, kidney, and so forth. The physicochemical property data of the novel coronavirus mainly come from the study of SARS-CoV. The virus is sensitive to ultraviolet light and heat. Exposure to 56°C for 30 minutes and lipid solvents, such as ether, 75% ethanol, chlorine-containing disinfectant, peracetic acid, and chloroform, can effectively inactivate the virus. Chlorhexidine has not been effective in inactivating the virus.

| EPIDEMI OLOG I C AL FE ATURE S OF N CP AMONG THE ELDERLY
A total of 82 218 cases of NCP had been diagnosed in China up to March 28, 2020. Epidemiological studies 1,2,[6][7][8] show that at the early stage, the virus was transmitted to humans from wildlife, then from human to human, which caused an outbreak of infected people.
Currently, patients infected by the novel coronavirus are the main source of infection; asymptomatic infected people can also be an infectious source. Transmission of the virus happens mainly through respiratory droplets and close contact. There is the possibility of aerosol transmission in a relatively closed environment with a long exposure to high concentrations of aerosol. 9 The WHO estimated that the basic reproduction number (R 0 ) of novel coronavirus is 1.4-2.5. 10 Based on early research from 425 patients, the estimated R 0 is 2.2. 6 A later study from 4021 patients showed that the estimated R 0 was 3.77 (range, 2.23-4.82), which shows that the transmissibility of novel coronavirus is equivalent to that of SARS-CoV and higher than that of MERS-CoV. 3 Some studies also show that the transmissibility of novel coronavirus is higher than that of SARS-CoV. 11 Up to March 28, 2020, the cases of death from NCP had reached 3301 with a case fatality rate of 4.0%. According to the available data, the mortality rate of NCP is lower than that of SARS-CoV (9.6%) and MERS-CoV (34%). 12 People are commonly susceptible to 2019-nCoV, especially the elderly with comorbidities, such as diabetes, hypertension, cardiovascular disease, and cerebrovascular disease. 1,2 The elderly are more likely to have severe cases and to require intensive care unit (ICU) care, 2,3 and this population has a high mortality rate. A study 13 of 1099 patients diagnosed with 2019-nCoV showed that the median age of patients was 47.0 years with 15.1% of all patients and 27% of severely ill patients aged over 65 years, and a median incubation period of 3.0 days (range, 0 to 24 days). An analysis from the research of 4021 diagnosed patients showed that nearly half (47%) of the patients were aged over 50 years and 1052 patients (26.2%) were aged over 60 years. The mortality of patients (some with complications) aged over 60 years (5.3%) was significantly higher than that of those aged under 60 years (5.3%). 3

| P OSS IB LE MECHANIS M OF N CP IN THE ELDERLY WITH HI G H RIS K OF INFEC TI ON
A major reason for the widespread transmission of the novel coronavirus in the population is the lack of immunocompetence, and there is no specific medicine for this virus. In healthy young people with normal immunity, the virus can be effectively eliminated by rapidly mobilizing the body's immune function.
There are many age-related variations in the respiratory and immune systems. 15,16 As for the elderly, there are many variations in the respiratory system's physiological function caused by the change of pulmonary anatomical structure and muscle atrophy, such as the weakening of airway clearance, the reduction of lung reserve, and the depression of defensive barrier function. In addition, pro-inflammatory cytokines baselines in the tissue and circulation of the elderly rise with age, especially interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), resulting in a condition known as "inflammatory senescence." Corresponding to inflammatory senescence, the body's immune response to pathogenic threaten or tissue damage is blunt, called "Immunosenescence." With age, the function of innate immunity and adaptive immunity declines; the discernment, chemotaxis, and phagocytosis of macrophages, natural killer cells, and neutrophils downgrade; and the diversity of the T-cell receptor (TCR) decreases. Furthermore, at the age of 60 years, the thymus that produces immature T-cells is replaced by adipose tissue, which leads to the accumulation of memory T-cells and effector T-cells and results in the decrease of immature T-cells. Meanwhile, the B-cells' ability to produce antibodies declines with age, which may cause hypoimmunity.
Inflammatory senescence and immunosenescence make individuals susceptible to novel coronavirus. The elderly in morbid states, such as chronic obstructive pulmonary disease or extra-pulmonary organ system diseases, are more likely to have severe respiratory infections, which causes the high mortality in elderly patients with NCP. The specific mechanism by which inflammatory factor storms are more likely to develop into acute respiratory failure in the elderly infected with novel coronavirus is unknown. It is still to be studied whether this mechanism is associated with the inflammatory imbalance that leads to disruption of pulmonary immune homeostasis and/ or the decline of innate immunity and adaptive immunity that aggravate novel coronavirus transmission, which leads to the imbalance response of pro-inflammatory and anti-inflammatory cytokines. 17 The novel coronavirus mainly leads to pulmonary infection, which increases the heart's workload, causes hyperglycemia, and makes it harder to control the infection. The characteristics of multisystem disease in the elderly make it a complex condition with all the diseases interplaying with each other, which increases the difficulty of treatment.

| CLINIC AL MANIFE S TATI ON OF N CP
Based on a current epidemiological survey, the incubation of NCP is 1-14 days, and mostly 3-7 days. The most common symptoms are fever, dry cough, and weakness. Nasal congestion, runny nose, sore throat, emesis, and diarrhea are found in some cases. Severe patients develop dyspnea and/or hypoxemia after 1 week and may progress rapidly to acute respiratory distress syndrome (ARDS), septic shock, refractory metabolic acidosis, coagulopathy, multiple organ

| L ABOR ATORY TE S T AND CHE S T IMAG ING FOR N CP
In the early stages of the disease, peripheral white blood cell count is normal or decreased and the lymphocyte count is decreased. Some patients have elevated liver enzymes, muscle enzymes, and myoglobin. Most patients have elevated C-reactive protein and erythrocyte sedimentation rate and normal procalcitonin. The levels of some inflammatory cytokines, such as IL-2, TNF-α, IL-6, and interferon-γ, are normal or higher. In severe cases, D-dimer increases and peripheral blood lymphocytes progressively decrease.
In the early stage, chest imaging shows multiple small patchy shadows and interstitial changes, which are more apparent in the peripheral zone of the lungs. As the disease progresses, imaging shows multiple ground-glass opacities and infiltration in both lungs. In severe cases, pulmonary consolidation may occur. However, pleural effusion is rare.
The elderly often suffer from chronic diseases that may effect and disturb the auxiliary examinations, which should be considered minutely in the process of treatment. For example, the elderly may have an increase in blood parameters and procalcitonin earlier than other patients, which is caused by co-bacterial infection; they may experience patient delay caused by atypical symptoms, which makes the initial manifestation of laboratory examination atypical; and underlying pulmonary diseases may lead to the early manifestation of atypical pulmonary imaging and, under these circumstances, the dynamic observation of past imaging data and imaging features is more meaningful.

| D IAG NOS TI C CRITERIA FOR N CP
We recommend the adoption of the criteria in the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial version 7)." 9 The details are as follows:

| S PECIAL PROB LEMS AMONG ELDERLY PATIENTS DURING D IAG NOS IS OF N CP
For elderly patients, clinical typing must be accompanied by prospective judgment, such as the consideration of functional status of other systems, as lung lesions of elderly patients may be more likely to induce failure in other systems, which may even occur before respiratory failure. It is advisable to conduct a comprehensive assessment of elderly patients. By doing so, elderly high-risk patients who may tend to get severe/critical illness will be identified and provided intervention as soon as possible, which can improve the prognosis.

| Case finding and reporting
Once medical personnel at all levels and all types of institutions find suspected cases that meet the definition, they should immediately carry out single-person isolation treatment. After consultation of in-hospital experts or attending physicians, those who are still considered as suspected cases should be reported through direct network within 2 hours and led to the collection of specimens for virus nucleic acid testing, meanwhile transporting patients to designated hospital as soon as possible with safety ensured. Even patients with common respiratory pathogens who have had close contact with positive novel coronavirus patients are advised to take a timely novel coronavirus nucleic acid test. Suspected cases can be excluded if the respiratory pathogens in nucleic acid testing are negative (sampling interval must be at least 24 hours) and the IgM and IgG of the novel coronavirus-specific antibodies are still negative 7 days after onset.

| Treatment venue determined by the severity of the disease
Suspected and confirmed cases should be treated in a designated hospital with effective isolation and protection; suspected cases should receive isolated treatment in one single room separately while confirmed cases can be accommodated in the same room.
Critical cases should be treated in the ICU as early as possible.

| Hospitalization
a. General treatment: Allow patients to rest in bed and provide strengthening support therapy; ensure sufficient caloric intake for patients; monitor patients' water, electrolyte, and acid-base balances to maintain internal environment stability; and closely monitor vital signs and oxygen saturation.
b. Sputum drainage: The sputum-drainage ability of elderly patients can decrease and sometimes they need mechanical assistance. Assisted sputum drainage procedures should be strictly followed. Human immunoglobulin is a kind of passive immunity and no novel coronavirus infection has occurred before, with no related antibody, so human immunoglobulin should not be taken as routine use. If elderly patients still have low levels of immunoglobulin after testing, human immunoglobulin can be used as appropriate.
In severe cases, gamma globulin can be administered intravenously as appropriate.
l. For severe patients with low lymphocyte count and low cellular immune function, we recommend the use of thymosin α1. Elderly people should eat foods that are easily digested, eat more vegetables and fruits, drink water frequently, and avoid eating wild animals and rotten or expired food. Chilled poultry should be purchased through regular channels, and meat, eggs, and milk should be fully cooked before eating. Elderly people with poor appetite and eating inadequate food can take some protein and trace elements appropriately through nutritionally fortified foods, special medical formula foods, or nutrient supplements.
For all elderly people, attention should also be paid to avoid as- f. In special cases, when the ventilator must be cut off for airway operation, the standby function of the ventilator should be used to avoid airborne transmission caused by the ventilator's airflow; if the ventilator has no standby function, the Y-type nozzle should be blocked to avoid airborne transmission.

| Criteria for being discharged from hospital
Patients with a temperature returning to normal for more than 3 days, significantly improved respiratory symptoms, significantly absorbed pulmonary imaging inflammation, and respiratory pathogens nucleic acid testing showing negative for two consecutive times (sampling interval must be at least 24 hours) can be released from isolation or transferred to the appropriate department for treatment of other diseases. Combating against Novel Coronavirus Pneumonia, for his guidance and review of this paper.

CO N FLI C T S O F I NTE R E S T
Nothing to disclose.