Interpretations of “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)”
The outbreak of coronavirus disease 2019 (COVID-19) has led to significant global health challenges, prompting the National Health Commission of the People’s Republic of China to issue a series of updated guidelines to manage the pandemic. The “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)” was published on March 3, 2020, and represents a culmination of accumulated clinical experience and a deeper understanding of the disease. This version revises several key areas, including transmission routes, pathological features, clinical characteristics, diagnosis, triage, treatment, and discharge standards, compared to the sixth version. This article provides a comprehensive interpretation of the seventh version to enhance understanding of the protocol.
Transmission Routes
The seventh version of the protocol introduces environmental contamination by urinary and fecal viral shedding from patients with 2019 novel coronavirus (2019-nCoV) as a potential route of transmission. The virus has been detected in the excreta of COVID-19 patients, suggesting that contamination by feces and urine could increase the risk of transmission. While it is widely accepted that 2019-nCoV is primarily transmitted through droplets, close contact, and, under certain circumstances, aerosols, the possibility of fecal-oral transmission requires further investigation. The protocol emphasizes the importance of frequent hand sanitization, well-ventilated lavatories, and unobstructed drains to mitigate this risk, aligning with recommendations from the World Health Organization.
Pathological Features
The updated protocol provides detailed information on the pathological changes observed in various organs of COVID-19 patients, based on autopsy findings and biopsy results. Gross examination of the lungs reveals varying degrees of consolidation with areas of hemorrhage and necrosis. Histological examination shows alveolar edema, extensive fibrin exudation, and hyaline membrane formation, with some areas exhibiting organized exudation and interstitial fibrosis. Cellular infiltration, primarily by monocytes, macrophages, and multinucleated syncytial cells, is another typical pulmonary manifestation. Notably, lymphocytes are not prominently mentioned in cellular infiltration, consistent with previous reports of persistent lymphopenia in non-survivors. Type II alveolar epithelial cells show extensive hyperplasia, with some necrosis and desquamation. Postmortem studies confirm the persistence of 2019-nCoV in lung tissue, particularly in patients who experienced diffuse alveolar damage, rapidly evolving pulmonary fibrosis, and respiratory failure.
Beyond the lungs, COVID-19 affects multiple organs, including the spleen, lymph nodes, bone marrow, heart, blood vessels, liver, kidney, brain, and gastrointestinal system. Critically ill patients often develop complications such as acute cardiac injury, acute kidney injury, abnormal coagulation function, shock, and multi-organ dysfunction. Pathological findings indicate that 2019-nCoV targets organs of the immune system, such as the spleen and lymph nodes, highlighting the role of impaired immune function in disease progression. Although pathological studies have improved understanding of the etiopathogenetic mechanisms, the exact mechanisms underlying COVID-19 development remain unclear due to the limited number of autopsies and scarcity of data from patients in the early and middle stages of the disease.
Clinical Characteristics
The seventh version of the protocol includes details on clinical manifestations in specific populations, such as children and newborns, who may present with atypical symptoms. However, there is currently no significant difference in clinical manifestations between pregnant and non-pregnant women or adults of reproductive age. The guidelines on laboratory examinations are divided into two sections: general laboratory investigations and pathogen detection. Pathogen detection methods, including reverse transcription-polymerase chain reaction (RT-PCR) and metagenomics next-generation sequencing, are clearly described. The protocol recommends collecting lower respiratory tract specimens due to their higher positivity rate.
A significant highlight of the seventh version is the inclusion of serological testing for 2019-nCoV-specific immunoglobulin (Ig)M and IgG antibodies as an aid in diagnosis. Serological testing methods, such as the colloidal gold method, chemiluminescence method, and enzyme-linked immunosorbent assay, have been widely used for diagnosing various infectious diseases and are expected to enhance the efficiency of COVID-19 diagnosis. However, questions remain regarding the reliability of new serological testing kits, the duration of the window period, and the optimal time for sample collection. Further investigations are needed to address these issues. The sensitivity and specificity of COVID-19-specific antibody detection are reported to be nearly 90%, indicating that serological testing holds great promise for diagnosis. Serological testing not only compensates for the limitations of nucleic acid detection by improving diagnostic accuracy and discharge standards but also minimizes the risk of cross-infection during pharyngeal swab collection. Additionally, serological testing plays a crucial role in evaluating the patient’s immune status and screening for individuals with a high neutralizing-antibody titer, who are valuable sources of convalescent plasma for therapy.
Diagnosis and Triage
The seventh version of the protocol defines clustered onset and emphasizes the diagnostic value of serological testing. COVID-19 can be confirmed based on one of the following criteria: positive COVID-19-specific IgM and IgG expression, a conversion from negative to positive on testing for specific IgG, and a four-fold increase in the IgG titer during the recovery period compared with the acute phase. Early indicators of disease worsening and progression are also highlighted in the updated protocol. Retrospective observational studies have identified prognostic factors for patients at risk of developing severe disease, including progressive lymphopenia, gradually increasing levels of pro-inflammatory cytokines and lactate dehydrogenase, and rapid exacerbation of pulmonary injury. These factors are closely associated with the prognosis of COVID-19 patients, indicating that cytokine storms, immune dysfunction, and imbalanced internal homeostasis play pivotal roles in disease progression. The protocol also provides detailed indicators for disease progression in children with COVID-19.
Therapeutic Options
The seventh version of the protocol recommends the use of mixed gases, with 66.6% hydrogen and 33.3% oxygen inhalation. While there are no new additions to the list of antiviral agents, the usage of previously suggested agents is seriously restricted, with clear indications for their routes of administration, dosage, side effects, contraindications, and drug interactions. Currently, there is no evidence from randomized controlled trials to support a specific drug treatment against 2019-nCoV, leading to varying recommendations among hospitals, regions, and guidelines. The recommendation regarding the use of corticosteroids remains unchanged, and their use remains controversial. Short-term corticosteroid therapy (80 mg/day for less than 5 days) is considered only for patients presenting with ongoing deterioration of the oxygenation index, rapid progression of infiltrates on radiological imaging, or excessive activation of the immune response.
A more comprehensive and detailed treatment strategy for severely and critically ill patients is included in the updated protocol. Recent studies suggest that the novel coronavirus may target multiple organs, leading to multiple organ dysfunction syndrome in advanced stages. The key objectives of COVID-19 treatment are to improve symptoms and underlying diseases, actively prevent and control potential complications, and provide timely measures to support organ function. Lung-protective ventilation strategies are recommended for patients requiring invasive mechanical ventilation, and detailed settings of ventilation parameters are provided. Extracorporeal life support, including extracorporeal membrane oxygenation, is considered for patients with hypoxemia refractory to invasive mechanical ventilation, with specific refinements in indications and timing. The protocol emphasizes the importance of monitoring methods for critically ill patients, including the use of the pulse index continuous cardiac output device, invasive blood pressure monitoring, and critical care ultrasonography. Continuous renal replacement therapy is recommended for patients with acute kidney injury and severe instability of the internal environment. Plasmapheresis can alleviate cytokine storms, and convalescent plasma therapy is recommended as a last resort to improve the prognosis of severely ill patients.
Immunotherapy is described as a therapeutic option for the first time in the seventh version. Recent reports indicate that serum levels of inflammatory mediators are significantly higher in severely ill patients than in those with milder disease. Tocilizumab, a humanized antibody for the interleukin-6 receptor, has been proposed as a therapeutic agent for patients with extensive lung injury and elevated interleukin-6 levels. Tocilizumab is widely used for treating autoimmune diseases and is approved by the US Food and Drug Administration for decreasing cytokine-release syndrome events due to CD19-specific chimeric antigen receptor T-cell therapy in acute lymphoblastic leukemia.
Discharge Standards
The seventh version stipulates that patients should continue quarantine under self-supervision for 14 days following discharge from the hospital or discontinuation of quarantine, with a proposed clinical follow-up. A recent study reported that a proportion of recovered COVID-19 patients continued to test positive for 2019-nCoV on RT-PCR. The exclusion criteria for suspected cases have been strictly redefined, requiring two consecutive negative RT-PCR test results and negative results for infection-specific IgM and IgG after 7 days of illness onset. These updates aim to facilitate better control and management of the COVID-19 pandemic.
Conclusion
The “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)” provides comprehensive guidelines for managing COVID-19, incorporating the latest clinical experience and research findings. The protocol addresses key aspects of transmission routes, pathological features, clinical characteristics, diagnosis, triage, treatment, and discharge standards, offering valuable insights for healthcare professionals in the fight against the pandemic. Continued research and updates to the protocol will be essential to further refine diagnostic and therapeutic strategies and improve patient outcomes.
doi.org/10.1097/CM9.0000000000000866
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