2021年 · 第01卷第01期

A century ago, an imported plague epidemic broke out in Northeast China. At that time, Mr. Liande Wu was the person responsible for handling the outbreak situation. China promptly took measures such as quarantine, isolation, and diagnosis and treatment and suc-cessfully eliminated the severe infectious disease that shocked the world in 4 months. At present, the COVID-19 epidemic broke out in Wuhan, China. Under the leadership of the Communist Party of China and Chinese authorities, China has adopted comprehensive measures such as early detection and diagnosis, treatment, and isolation to control the epidemic within 3 months, embodying China’s considerable anti-epidemic spirit: life is supreme, the whole country is of one mind, regardless of life and death, respecting science, and destiny together. The prompt actions taken, efficiency, and experience that China has shown indicate that it has gradually been at the forefront of the global fight against infectious diseases. However, with the exception of China and a few countries, COVID-19 remains to threaten human health worldwide.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in over 110 million confirmed cases and more than 2.4 million deaths globally as of February 23, 2021.^[1]China succeeded in containing the nationwide spread of COVID-19 by implementing a lockdown in the city of Wuhan, where the first outbreak occurred. Following the containment of the first outbreak, China experienced more than a dozen small clusters of cases in other cities due to virus transmission by travelers and cold-chain transmission. However, widespread transmission of the virus was prevented by implementing strict quarantine policies and social distancing measures. Although great progress has been made in under-standing the epidemiology, virology, immune response, and clinical outcomes of this disease 1 year after the start of the pandemic, the origin of the virus remains unresolved.

COVID-19 is another major pandemic of viral infectious disease in the 21st century. Since the first case was reported in Wuhan, China, in December 2019, COVID-19 has resulted in more than 100 million confirmed cases and more than 2 million deaths. COVID-19 has been considered to be a systemic inflammatory response syndrome caused by SARS-CoV-2 infection, mainly with pulmonary lesions. Most patients have mild symptoms and a good prognosis, but severe or critical cases can lead to death. Otherwise, there is no effective antiviral drug to treat COVID-19.

Coronavirus Disease 2019 (COVID-19) has become a major global public health pandemic. China was the first country to report the epidemic situation, which quickly identified the pathogen, and released the novel coronavirus gene sequence globally. Thus, China has played an essential role in the global fight against COVID-19. Since the outbreak of the epidemic, the Chinese government and citizens have pursued robust prevention and control measures, including wearing masks, hand hygiene, social distancing, etc. Large-scale nucleic acid testing has been fully implemented and has resulted in early detection, reporting, quarantine, and treatment. China’s epidemic situation has been generally brought under control, and the fatality rate has been effectively controlled.^[1,2,3,4]Recently there are sporadic cases of COVID-19 in China. Of the locally transmitted cases reported at January 20, 2021, 68 were reported in Heilongjiang, 33 in Jilin, 20 in Hebei, two each in Beijing and Shanxi, and one in Shandong, the National Health Commission reported.^[5]

As an emerging acute respiratory infection, the coronavirus disease 2019 (COVID-19) has become a major public health emergency that threatens global health. Through active prevention, control, and treatment measures, China has essentially brought the situation within its borders under control. Only sporadic outbreaks and imported cases remain in some parts of the country. However, as the virus is still spreading across the globe, the pandemic may persist for a longer period of time, and the risk of COVID-19 re-emerging in China still lingers. In order to further observe the principles of early detection, reporting, quarantine, and treatment of COVID-19 patients, to increase recovery rates and to lower fatality rates, we have updatedthe Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 7th Edition)by summarizing China’s recent clinical experience and referencing treatment guidelines issued by the World Health Organization and other countries. Thus,the Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 8th Edition)was developed.

The development of severe coronavirus disease 2019 (COVID-19) is associated with systemic hyperinflammation, which drives multi-organ failure and death. Disease deterioration tends to occur when the virus is receding; however, whether other factors besides viral products are involved in the inflammatory cascade remains unclear.

Twenty-eight COVID-19 patients with laboratory-confirmed SARS-CoV-2 infection hospitalized at the Fifth Medical Center of Chinese PLA General Hospital from January 23 to February 20, 2020 and nine healthy donors during the same period were recruited in the study. COVID-19 patients were grouped as mild, moderate, severe based on disease severity. Plasma damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), calprotectin (S100A8/A9), surfactant protein A (SP-A), cold-inducible RNA-binding protein (CIRBP), and Histone H4 were detected by ELISA assay, and analyzed in combination with clinical data. Plasma cytokines, chemokines and lymphocytes were determined by flow cytometry.

Plasma levels of HMGB1 (38292.3 ± 4564.4 vs. 32686.3 ± 3678.1, P= 0.002), S100A8/A9 (1490.8 ± 819.3 vs. 742.2 ± 300.8, P= 0.015), and SP-A (6713.6 ± 1708.7 vs. 5296.3 ± 1240.4, P= 0.048) were increased in COVID-19 patients compared to healthy donors, while CIRBP (57.4 ± 30.7 vs. 111.9 ± 55.2, P= 0.004) levels decreased. Five DAMPs did not vary among mild, moderate, and severe patients. Moreover, SP-A levels correlated positively with inflammatory cytokines and negatively with time elapsed after symptom onset, whereas CIRBP showed an opposite pattern.

These findings suggest SP-A may involve in the inflammation of COVID-19, while CIRBP likely plays a protective role. Therefore, DAMPs represent a potential target in the prevention or treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.

In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality.

The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than 10 × 10⁹/L, neutrophil count of more than 7 × 10⁹/L, lymphocyte count of less than 0.8 × 10⁹/L, platelet count of less than 100 × 10⁹/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively.

We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.

Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver.

Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People’s Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines.

The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P= 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P= 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells.

Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.