China Releases Trial Version 5 of COVID-19 Diagnosis and Treatment Protocol, First to Identify Asymptomatic Carriers as Potential Sources of Transmission

Since December 2019, multiple cases of pneumonia caused by the novel coronavirus have been identified in Wuhan City, Hubei Province. As the epidemic has spread, similar cases have subsequently been detected in other regions of China and abroad. Classified as an acute respiratory infectious disease, it has been included as a Category B infectious disease under the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases, but is managed in accordance with measures for Category A infectious diseases.

As understanding of the disease deepened and clinical experience accumulated, starting at 15:00 on February 2, Academician Zhong Nanshan held a video conference under the auspices of the Guangdong Provincial Health Commission with heads of relevant departments of the National Health Commission, as well as experts nationwide and those in Hubei Province. They conducted research and discussions on multiple topics, including the revision of the Diagnosis and Treatment Protocol for Novel Coronavirus-Infected Pneumonia, resulting in the formulation of the Diagnosis and Treatment Protocol for Novel Coronavirus-Infected Pneumonia (Trial Version 5) on February 3.

The newly revised fifth edition of the “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia” offers strong guidance and practical operability, with a focus on optimizing the treatment of critically ill and severe cases.

VCBeat noted that the fifth edition of the interim diagnosis and treatment protocol for novel coronavirus pneumonia (COVID-19) first proposed that asymptomatic individuals could also serve as sources of infection. It confirmed that the main routes of viral transmission are through respiratory droplets and contact, while transmission via aerosols and the digestive tract remains to be clarified. Below is the full text of the fifth edition of the interim diagnosis and treatment protocol for COVID-19 (italicized text indicates revisions or additions):

I. Etiological Characteristics

Novel coronavirus is a β-coronavirus. It is enveloped, with particles that are spherical or oval in shape, often pleomorphic, and 60–140 nm in diameter. Its genetic characteristics differ significantly from those of SARSr-CoV and MERSr-CoV. Current studies show that it shares more than 85% sequence homology with bat SARS-like coronavirus (bat-SL-CoVZC45). During in vitro isolation and culture, 2019-nCoV can be detected in human respiratory epithelial cells within approximately 96 hours, whereas isolation and culture in Vero E6 and Huh-7 cell lines require about 6 days.

Knowledge of the physical and chemical properties of coronaviruses is largely derived from studies on SARS-CoV and MERS-CoV. The virus is sensitive to ultraviolet light and heat. It can be effectively inactivated by exposure to 56°C for 30 minutes, as well as by lipid solvents such as ether, 75% ethanol, chlorine-containing disinfectants, peracetic acid, and chloroform. Chlorhexidine is not effective in inactivating the virus.

II. Epidemiological Characteristics

(I) Source of infection.

The primary source of infection currently identified is patients infected with the novel coronavirus.Asymptomatic individuals can also serve as sources of infection.

(II) Transmission routes.

Respiratory droplets and contact transmission are the main routes of transmission.Transmission routes such as aerosol and gastrointestinal tract remain to be clarified.

(III) Susceptible Populations.

The general population is universally susceptible.

III. Clinical Features

(I) Clinical Manifestations.

Based on current epidemiological investigations,The incubation period is 1–14 days, mostly 3–7 days.

The main manifestations are fever, fatigue, and dry cough. A small number of patients also experience symptoms such as nasal congestion, runny nose, sore throat, and diarrhea.Severe cases often develop dyspnea and/or hypoxemia one week after onset.Severe cases can rapidly progress to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, and coagulation disorders. Notably, patients with severe or critical illness may present with only low-to-moderate fever or even no obvious fever during the course of the disease.

Mild cases present only with low-grade fever and mild fatigue, without manifestations of pneumonia.

Based on the cases treated so far, the prognosis is favorable for most patients, while a minority present with critical conditions. Elderly individuals and those with chronic underlying diseases have a poorer prognosis. Pediatric cases generally exhibit milder symptoms.

(II) Laboratory Tests.

In the early stage of the disease, the total peripheral white blood cell count is normal or decreased, and the lymphocyte count is reduced.Some patients may present with elevated liver enzymes, LDH, muscle enzymes, and myoglobin.Elevated troponin levels may be observed in some critically ill patients.Most patients exhibit elevated C-reactive protein (CRP) and erythrocyte sedimentation rate, with normal procalcitonin levels. In severe cases, D-dimer levels are elevated, and there is a progressive decrease in peripheral blood lymphocytes.

InNasopharyngeal swab,Novel coronavirus nucleic acid can be detected in specimens such as sputum, lower respiratory tract secretions, blood, and feces.

(3) Chest Imaging.

Early stages present with multiple small patchy opacities and interstitial changes, predominantly in the peripheral lung zones. These may progress to multiple ground-glass opacities and infiltrates in both lungs; severe cases can develop pulmonary consolidation, while pleural effusion is rare.

IV. Diagnostic Criteria

(I) Suspected Cases.

Comprehensive analysis based on the following epidemiological history and clinical manifestations:

1. Epidemiological History

（1) Had a travel or residence history in Wuhan and surrounding areas, or in other communities with reported cases, within 14 days before the onset of illness;

(2) Had contact within 14 days prior to onset with febrile patients or patients with respiratory symptoms from Wuhan and surrounding areas, or from communities with reported cases;

(3) Clustered onset of illness;

(4) History of contact with individuals infected with the novel coronavirus. Individuals infected with the novel coronavirus refer to those who test positive for pathogenic nucleic acid.

2. Clinical Manifestations

(1) Fever and/or respiratory symptoms;

(2) Exhibiting the aforementioned radiological features of pneumonia;

(3) In the early stage of onset, the total white blood cell count is normal or decreased, or the lymphocyte count is reduced.

Presence of any one epidemiological criterion, along with any two clinical manifestations.

(II) Confirmed cases.

Suspected cases with one of the following etiological evidence:

1. Positive result for SARS-CoV-2 nucleic acid by real-time fluorescent RT-PCR testing of respiratory or blood specimens;

2. Viral gene sequencing of respiratory or blood specimens shows high homology with the known novel coronavirus.

V. Clinical Classification

(1) Mild cases.

Mild clinical symptoms; no radiological evidence of pneumonia.

(II) Common Type.

Presenting with symptoms such as fever and respiratory issues, with imaging findings indicative of pneumonia.

(3) Severe cases.

Meets any of the following criteria:

1. Respiratory distress, RR ≥ 30 breaths/min;

2. Resting peripheral capillary oxygen saturation (SpO₂) ≤93%;

3. Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa).

(4) Critical Type.

Individuals meeting any of the following criteria:

1. Development of respiratory failure requiring mechanical ventilation;

2. Development of shock;

3. ICU monitoring and treatment are required for concurrent failure of other organ systems.

VI. Differential Diagnosis

It is primarily necessary to differentiate from other known viral pneumonias, such as those caused by influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, and SARS coronavirus, as well as from Mycoplasma pneumoniae pneumonia, chlamydial pneumonia, and bacterial pneumonia. Furthermore, differentiation from non-infectious diseases, such as vasculitis, dermatomyositis, and organizing pneumonia, is also required.

VII. Case Detection and Reporting

Medical personnel at medical institutions of all levels and types shall immediately initiate isolation treatment upon identifying suspected cases that meet the case definition. If, following consultation with in-house experts or the attending physician, the case is still considered suspected, it must be reported directly via the online system within 2 hours, and specimens shall be collected for nucleic acid testing for the novel coronavirus.On the Premise of Ensuring Transport SafetyTransfer suspected patients to designated hospitals as soon as possible. For patients who have had close contact with individuals infected with the novel coronavirus, etiological testing for the novel coronavirus is recommended in a timely manner, even if tests for common respiratory pathogens are positive.

A suspected case can be ruled out only after two consecutive negative nucleic acid tests for respiratory pathogens, with samples collected at least one day apart.

VIII. Treatment

(1) Determine the treatment setting based on the patient's condition.

1. Suspected and confirmed cases should be isolated and treated at designated hospitals with effective isolation and protective conditions; suspected cases should be isolated in single rooms, while confirmed cases may be accommodated in the same ward.

2. Critical cases should be admitted to the ICU for treatment as early as possible.

(II) General Treatment.

1. Bed rest, strengthened supportive care, and ensuring adequate caloric intake; attention to water and electrolyte balance to maintain internal homeostasis; close monitoring of vital signs, oxygen saturation, etc.

2. Monitor complete blood count, urinalysis, C-reactive protein (CRP), biochemical parameters (liver enzymes, cardiac enzymes, renal function, etc.), coagulation profile, and arterial blood gas analysis according to the patient's condition.Cytokine testing may be performed where conditions permit.Follow-up chest imaging.

3. Promptly administer effective oxygen therapy, including nasal cannula, face mask oxygen delivery, and high-flow nasal oxygen therapy.

4. Antiviral therapy: Currently, there is no confirmed effective antiviral treatment. A trial of alpha-interferon via nebulized inhalation may be considered (5 million IU per dose for adults).or an equivalent dose,Add 2 mL of sterile water for injection, twice daily); lopinavir/ritonavir (200 mg/50 mg per capsule), 2 capsules each time, twice daily,Ribavirin may be added via intravenous infusion (500 mg per dose for adults, twice daily). Attention should be paid to adverse reactions associated with lopinavir/ritonavir, such as diarrhea, nausea, vomiting, and hepatic impairment, as well as potential drug-drug interactions.

5. Antimicrobial Therapy: Avoid blind or inappropriate use of antimicrobial agents, particularly the combined use of broad-spectrum antimicrobials.

(3) Treatment of severe and critical cases.

1. Treatment Principles: On the basis of symptomatic treatment, actively prevent and manage complications, treat underlying diseases, prevent secondary infections, and provide timely organ function support.

2. Respiratory Support:

(1) Oxygen therapy: Patients with severe disease should receive oxygen via nasal cannula or face mask, and timely assessment should be conducted to determine whether respiratory distress and/or hypoxemia have been alleviated.

(2) High-flow nasal cannula oxygen therapy or non-invasive mechanical ventilation: When respiratory distress and/or hypoxemia cannot be alleviated after standard oxygen therapy, high-flow nasal cannula oxygen therapy or non-invasive ventilation may be considered. However, the failure rate of non-invasive ventilation in such patients is high, and close monitoring should be conducted. If there is no improvement or even deterioration within a short period (1-2 hours), endotracheal intubation and invasive mechanical ventilation should be promptly performed.

(3) Invasive Mechanical Ventilation: Adopt a lung-protective ventilation strategy, specifically using low tidal volumes (4–8 mL/kg of ideal body weight) and low inspiratory pressures (plateau pressure <30 cmH2O), to minimize ventilator-induced lung injury. Sedatives and analgesics should be administered to patients receiving invasive mechanical ventilation. Neuromuscular blocking agents should be promptly initiated if patient-ventilator asynchrony persists despite sedation, resulting in an inability to control tidal volume, or if refractory hypoxemia or hypercapnia develops. Once the patient’s condition stabilizes, the dosage of neuromuscular blocking agents should be tapered and discontinued as soon as possible.

(4) Rescue Therapy: For patients with severe ARDS, lung recruitment maneuvers are recommended. When staffing resources are adequate, prone position ventilation should be administered for more than 12 hours per day. If prone position ventilation yields suboptimal results, extracorporeal membrane oxygenation (ECMO) should be considered as soon as possible, conditions permitting.

3. Circulatory Support: On the basis of adequate fluid resuscitation, improve microcirculation, use vasoactive drugs, and perform hemodynamic monitoring when necessary.

4. Other Treatment Measures

Glucocorticoids may be used for a short term (3–5 days) as appropriate, based on the severity of dyspnea and progression of chest imaging findings; the recommended dose should not exceed the equivalent of methylprednisolone 1–2 mg/kg/day.It should be noted that higher doses of glucocorticoids may delay the clearance of coronaviruses due to their immunosuppressive effects;Xuebijing Injection can be administered intravenously at a dose of 100 mL per infusion, twice daily; intestinal microbiota modulators may be used to maintain intestinal microbial homeostasis and prevent secondary bacterial infections; where conditions permit,For critically ill patients with a heightened inflammatory response, the use of extracorporeal blood purification techniques may be considered;Convalescent plasma therapy may be employed when conditions permit.

Patients often experience anxiety and fear; psychological counseling should be strengthened.

(4) Traditional Chinese Medicine Treatment.

This disease falls within the category of “epidemic diseases” in Traditional Chinese Medicine (TCM). The etiology is attributed to contraction of epidemic pathogenic qi. Based on the patient’s condition, local climatic characteristics, and individual constitutions, healthcare providers in different regions may refer to the following guidelines for syndrome differentiation and treatment.

1. Medical Observation Period

Clinical Manifestation 1: Fatigue Accompanied by Gastrointestinal Discomfort

Recommended Chinese patent medicines: Huoxiang Zhengqi Capsules (Pills, Liquid, Oral Solution)

Clinical Manifestation 2: Fatigue with Fever

Recommended Chinese patent medicines: Jinhua Qinggan Granules, Lianhua Qingwen Capsules (Granules), Shufeng Jiedu Capsules (Granules), Fangfeng Tongsheng Pills (Granules)

2. Clinical Treatment Phase

(1) Initial Stage: Cold-Dampness Stagnating in the Lungs

Clinical Manifestations: Aversion to cold with fever or no fever, dry cough, dry throat, fatigue and weakness, chest tightness, epigastric fullness, nausea or vomiting, and loose stools. The tongue is pale or light red with a white, greasy coating; the pulse is soggy.

Recommended Prescription: Atractylodes Rhizome 15g, Tangerine Peel 10g, Magnolia Bark 10g, Agastache 10g, Tsaoko Fruit 6g, Raw Ephedra 6g, Notopterygium Root 10g, Fresh Ginger 10g, Betel Nut 10g

(2) Mid-stage: Epidemic toxin obstructing the lungs

Clinical Manifestations: Persistent fever or alternating chills and fever, cough with scanty sputum or yellow phlegm, abdominal distension, and constipation. Chest tightness, shortness of breath, coughing with wheezing and dyspnea, and exertional asthma. The tongue is red with a yellow, greasy or yellow, dry coating; the pulse is slippery and rapid.

Recommended Prescription: Apricot Kernel 10g, Raw Gypsum 30g, Trichosanthes Fruit 30g, Raw Rhubarb 6g (added later), Raw and Honey-fried Ephedra 6g each, Descurainia Seed 10g, Peach Kernel 10g, Tsaoko Amomum Fruit 6g, Areca Nut 10g, Atractylodes Rhizome 10g

Recommended Chinese patent medicines: Xiyanping Injection, Xuebijing Injection

(3) Critical Stage: Internal Closure and External Collapse

Clinical Manifestations: Dyspnea, shortness of breath upon exertion or need for assisted ventilation, accompanied by clouded consciousness, restlessness, sweating with cold extremities, a dark purple tongue body, a thick greasy or dry coating, and a floating, large, and rootless pulse.

Recommended Prescription: Ginseng 15g, Prepared Aconite Root (Hei Shun Pian) 10g (decoct first), Cornus Fruit 15g, taken with Suhexiang Pills or Angong Niuhuang Pills.

Recommended Chinese patent medicines: Xuebijing Injection, Shenfu Injection, Shengmai Injection

(4) Recovery Stage: Deficiency of Lung and Spleen Qi

Clinical Manifestations: Shortness of breath, fatigue and weakness, poor appetite with nausea and vomiting, epigastric fullness and distension, weak defecation effort, loose and unsatisfactory stools, pale and puffy tongue, and white greasy coating.

Recommended Prescription: Fa Ban Xia (Processed Pinellia Rhizome) 9g, Chen Pi (Dried Tangerine Peel) 10g, Dang Shen (Codonopsis Root) 15g, Zhi Huang Qi (Honey-fried Astragalus Root) 30g, Fu Ling (Poria) 15g, Huo Xiang (Agastache/Patchouli Herb) 10g, Sha Ren (Amomum Fruit) 6g (added near the end of decoction)

IX. Criteria for Discontinuation of Isolation and Hospital Discharge

Patients may be discharged from isolation or transferred to the appropriate department for treatment of other conditions, provided that their body temperature has remained normal for more than three days, respiratory symptoms have significantly improved, and two consecutive negative results have been obtained from nucleic acid tests for respiratory pathogens (with at least one day between samples).

X. Principles of Patient Transfer

Implement in accordance with the “Work Plan for the Transfer of Cases of Pneumonia Caused by Novel Coronavirus Infection (Trial)” issued by our Commission.

XI. Hospital Infection Control

(1) Strictly implement standard precautions.

Healthcare personnel shall adhere to the principles of standard precautions and implement hospital infection control measures—including personal protective equipment use, hand hygiene, ward management, environmental ventilation, cleaning and disinfection of surfaces, and medical waste management—based on the risk of transmission associated with medical procedures, thereby minimizing the occurrence of healthcare-associated infections.

(II) Personal Protective Equipment for Healthcare Workers.

1. All medical personnel shall wear medical masks during diagnostic and therapeutic activities.

2. Pre-triage Area: Wear work uniforms and caps, and don surgical masks.

3. Fever clinics, respiratory outpatient clinics, emergency departments, infectious disease departments, and isolation wards: During routine diagnosis, treatment activities, and ward rounds, wear work attire, disposable isolation gowns, work caps, and medical protective masks. When collecting respiratory specimens, additionally wear goggles or face shields. When coming into contact with blood, body fluids, secretions, or excreta, additionally wear latex gloves. During procedures that may generate aerosols or splashes, such as endotracheal intubation, bronchoscopy, airway care, and sputum suctioning, wear medical protective masks, goggles or face shields, latex gloves, and medical protective clothing (disposable fluid-resistant isolation gowns may be added); wear powered air-purifying respirators (PAPRs) when necessary.

4. Medical personnel must strictly adhere to the established protocols for donning and doffing personal protective equipment (PPE). Wearing PPE outside the contaminated zone is prohibited to prevent cross-contamination between designated areas.

5. Medical institutions shall reasonably arrange working hours for medical personnel, strengthen symptom monitoring, and promptly conduct screening for individuals presenting with symptoms such as fever and cough.

(3) Other Precautions.

1. The passageways for medical personnel and patients in isolation wards shall be separated, and a buffer zone shall be provided for the medical personnel passageway.

2. Wearing gloves does not replace hand hygiene.

3. Patients and accompanying personnel should wear masks.