Shanghai expert consensus on clinical protocol for traditional Chinese medicine treatment of COVID-19 among the elderly population (second edition)



# Introduction
Shanghai is a metropolitan city with a large aging population, where 5.81 million people (23.4% of the overall population) are over 60 years old [bib_ref] A research agenda for aging in China in the 21st century, Fang [/bib_ref]. Data from China and Italy revealed a casefatality rate of 2.3% in patients with COVID-19, with more than 50% of the fatalities occurring in patients 50 years of age or older [bib_ref] Similarity in case fatality rates (CFR) of COVID-19/SARS-COV-2 in Italy and China, Porcheddu [/bib_ref]. In the largest reported series from Northern Italy, casefatality rate in patients 64 years or older was 36%, substantially higher than in younger patients [bib_ref] Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to..., Grasselli [/bib_ref]. Under the ongoing epidemic of coronavirus disease 2019 (COVID-19) caused by Omicron variant in Shanghai, traditional Chinese medicine (TCM) treatment is one tool that can be used for critical cases, especially to improve treatment efficacy among COVID-19 cases in the elderly population. This expert consensus is released based on the symptoms of COVID-19 caused by Omicron variant in conjunction with its etiology and pathogenesis specific to the elderly population, and based on the Protocol for Diagnosis and Treatment of COVID-19 (Trial 9th Edition). The TCM experts searched domestic and foreign studies, consulted with other experts, and discussed their ideas in order to formulate a common understanding of the topic. This consensus is based on existing research to develop a declarative document, focusing on feasible approaches for our current clinical reality.

## The application principles of tcm in the elderly population with covid-19
(1) The goals of TCM treatment are to shorten COVID-19 nucleic acid polymerase chain reaction negativity conversion time, slow disease progression, and reduce mortality. (3) For moderate cases with high-risk factors, severe to critical cases, or patients with poorly controlled underlying chronic diseases, clinicians should identify the treatment priorities between COVID-19 and these underlying diseases, and pay close attention to any changes in these underling conditions. A multidisciplinary team is recommended to establish individualized treatment strategy to address clinical factors associated with disease aggravation, halt or reverse disease progression and thus reduce mortality. (4) Elderly patients often have multiple underlying diseases.
TCM theory considers decline of healthy qi with age, which results in insidious onset of disease signs and symptoms. In these patients, early identification, diagnosis, and intervention of disease are important. When the patients present with fatigue, drowsiness, loss of appetite or decreased food intake, or constipation, along with decline of oxygen level, dynamic reduction in serum absolute lymphocyte count, dynamic elevation of inflammatory cytokines and blood coagulation indicators such as D-dimer, and notable progression of lung infiltration by chest imaging, initial intensive care is crucial to prevent mild or moderate cases progressing to severe or critical conditions. (5) For newly infected moderate cases with a deficiency of healthy qi, the treatment strategy is to replenish qi, clear heat and resolve dampness in order to rapidly halt disease progression. The recommended herbal formula for this strategy is shown in [fig_ref] Table 1: The basic formula for newly infected moderate cases [/fig_ref]. (6) For severe and critical cases, the treatment strategy is to clear the lung, dredge intestines, remove toxins, and cool blood. The recommended formula for this strategy is shown in [fig_ref] Table 2: The basic formula for severe and critical cases [/fig_ref].

## The primary tcm strategies for elderly population with covid-19
Elderly patients tend to experience a deficiency in healthy qi, weakness of the zang-fu organs, and poor circulation of qi and blood. Thus, elderly patients with COVID-19 are at risk of rapid deterioration because of the multiple underlying chronic diseases. When treating elderly patients with TCM, it is important to clear pathogenic factors while simultaneously working to protect and replenish healthy qi through invigorating the spleen and reinforcing the kidney, or activate blood. In choosing clinical treatment strategies, identifying the status or urgency of the disease pattern takes priority. Good clinical judgement takes into consideration how to balance the two treatment aspects between relieving acute symptoms in the short term, and protecting healthy qi for the long run. To help prioritize between removing pathogenic factors and reinforcing healthy qi, appropriate treatment strategies based on core symptoms and pathogenesis may include: (1) removing pathogenic factors being the major goal, supplemented by reinforcing healthy qi; (2) removing pathogenic factors and reinforcing healthy qi; (3) reinforcing healthy qi, securing yang and preventing collapse.
Timely administration of medicine and using accurate treatment strategies (e.g., fine-tuning the proportion of unblocking, clearing, and supporting strategies in a formula) are essential for regulation of the overall state. In addition to oral or intragastric administration, TCM injections are recommended for treating critical cases.
It is worth noting that the two recommended formulas can be modified according to the patient's actual conditions. Detailed modifications are explained as follows.
(1) For a persistent high fever with an excess pattern, the treatment strategy is to cool blood, remove toxins and dredge intestines. Add the following herbs [fig_ref] Table 3: Herbs recommended for persistent high fever [/fig_ref] to the recom-mended formulas. Chinese patent medicines [fig_ref] Table 4: Recommended Chinese patent medicines for persistent high fever [/fig_ref] are also recommended. Acupuncture treatment is suggested. Acupuncture points: Dazhui (GV14) and Quchi (LI11). (2) For altered state of consciousness, e.g. delirium, deficiency or excess should be distinguished. The treatment strategy for deficiency pattern is to protect fluids, replenish qi and nourish yin. Shengshaishen (Radix et Rhizoma Ginseng Cruda) 10 g or Xiyangshen (Radix Panacis Quinquefolii) 10 g (or their powder) is recommended for the formulas. Also, Shengmai Injection (20-60 mL) is also suggested by intravenous drip, twice a day. The treat- (5) For progressing infiltration of lung lesions seen on chest imaging, the treatment strategy is to clear heat and activate blood circulation. Add the following herbs [fig_ref] Table 9: Recommended herbs for aggravated infiltration lung lesions on chest imaging [/fig_ref] to the recommended formula for severe or critical cases. The recommended Chinese patent medicines are shown in [fig_ref] Table 1: The basic formula for newly infected moderate cases [/fig_ref]. (6) For persistent turbid greasy tongue coating, chest tightness, nausea, vomiting, headache, and restlessness due to qi stagnation and pathogenic factors hidden in the pleurodiaphragmatic interspace (known as Mo Yuan in Chinese medicine), the treatment strategy is to remove pathogenic factors out of the pleuro-diaphragmatic interspace and facilitate functional activities of qi. The following herbs [fig_ref] Table 1: The basic formula for newly infected moderate cases [/fig_ref] are recommended additions to the formulas. (7) For qi deficiency, it is important to invigorate qi as early as possible to help remove pathogenic factors. Chinese herbal formula modifications include adding Huangqi (Radix Astragali) up to 30-60 g and Dangshen (Radix Codonopsis) 15 g or Taizishen (Radix Pseudostellariae) 30 g to the recommended

## The primary tcm strategies for covid-19 in the elderly population with chronic underlying diseases
Since chronic underlying diseases have a critical role for increasing morbidity and mortality in elderly patients with COVID-19, it is important to determine the treatment priorities and place more emphasis on the chronic underlying diseases in order to halt disease progression and protect the Zang-fu organs in this population. Other measures include general medical care, sufficient management of the chronic underlying diseases, proper daily nutrition, supporting normal bowel movements and preventing aspiration pneumonitis. The recommended formulas or treatment strategies for three underlying diseases are listed as follows.
(1) For cases with chronic renal disease, the treatment strategy is to replenish qi, warm yang, activate blood and dredge intestines. The Chinese herbal formula should include an increased dose of Huangqi (Radix Astragali) to 30-90 g and the following additions [fig_ref] Table 1: The basic formula for newly infected moderate cases [/fig_ref] to the recommended formulas.
(2) For cases with chronic cardiac disease, the treatment strategy is to replenish qi, warm yang, activate blood and promote urination. Add the following herbs [fig_ref] Table 1: The basic formula for newly infected moderate cases [/fig_ref] This expert consensus was given only as a reference for clinical decision making. While treating individualized patients, doctors need to take all causative factors into consideration, identify the etiology, pathogenesis and symptoms, make treatment strategy based on pattern identification, and modify the herbal dosage regimen according to the patient's volume of fluid intake and output. Acupuncture treatment is suggested for once a day: use disposable filiform needles with a plastic guide tube, conduct even reinforcing-reducing manipulation, and retain the needles for 30 minutes for each treatment.
[fig] Funding: This study was supported by Shanghai Municipal Science and Technology Major Project (No. ZXS001-F4R4Z3), Shanghai Key Clinical Specialty (No. SHSLCZDZK05101) and Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (No. 20DZ2272200). [/fig]
[table] Table 1: The basic formula for newly infected moderate cases. [/table]
[table] Table 2: The basic formula for severe and critical cases. [/table]
[table] Table 3: Herbs recommended for persistent high fever. * Danshen (Radix et Rhizoma Salviae Miltiorrhizae) can be used interchangeably. [/table]
[table] Table 4: Recommended Chinese patent medicines for persistent high fever. [/table]
[table] Table 9: Recommended herbs for aggravated infiltration lung lesions on chest imaging. [/table]
[table] Table 6: Recommended Chinese patent medicines for excess phlegm heat syndrome. [/table]
[table] Table 7: Recommended herbs for excess patterns of constipation. [/table]
[table] Table 5: Recommended herbs for excess phlegm heat syndrome. [/table]
[table] Table 8: Recommended herbs for difficult expectoration of sticky sputum. [/table]