Volume 01 · Issue 01 · 2021

一个世纪前，中国东北爆发输入性鼠疫疫情。当时，吴连德先生是负责处理疫情的人员。中国及时采取检疫、隔离、诊治等措施，在4个月内成功消灭了这一震惊世界的严重传染病。当前，新冠肺炎疫情在中国武汉暴发。在中国共产党和中国当局领导下，中国采取早发现早诊断、早治疗、早隔离等综合措施，在3个月内控制住了疫情，体现了中国相当的抗疫精神：生命至上、举国同心、不分生死、尊重科学、命运与共。中国采取的迅速行动、展现的效率和经验表明，中国已逐渐走在全球抗击传染病的前列。然而，除中国和少数国家外，新冠肺炎仍然威胁着全球人类健康。

截至2021年2月23日，由严重急性呼吸系统综合症病毒2（新型冠状病毒）引起的COVID-19大流行已导致全球超过1.1亿例确诊病例和超过240万例死亡。^[1]中国通过在首次爆发疫情的武汉市实施封锁，成功遏制了新冠肺炎在全国范围内的传播。在第一次疫情得到控制后，由于旅行者传播病毒和冷链传播，中国在其他城市出现了十几起小型聚集性病例。然而，通过实施严格的隔离政策和社会距离措施，阻止了病毒的广泛传播。尽管在大流行开始1年后，在了解该疾病的流行病学、病毒学、免疫反应和临床结果方面取得了很大进展，但病毒的起源仍未解决。

新冠肺炎是21世纪又一大病毒性传染病大流行。自2019年12月中国武汉报告首例病例以来，新冠肺炎已导致超过1亿例确诊病例和超过200万例死亡。新冠肺炎一直被认为是由新型冠状病毒感染引起的全身性炎症反应综合征，以肺部病变为主。大多数患者症状轻微，预后良好，但重症或危重症病例可导致死亡。否则，就没有有效的抗病毒药物来治疗新冠肺炎。

冠状病毒疾病2019（新冠肺炎）已成为全球重大公共卫生疫情。我国是最早报告疫情的国家，迅速确定了病原体，并向全球发布了新型冠状病毒基因序列。因此，中国在全球抗击新冠肺炎的斗争中发挥了至关重要的作用。疫情发生以来，中国政府和公民采取了强有力的防控措施，包括戴口罩、手卫生、保持社交距离等。全面实施大规模核酸检测，做到了早发现、早报告、早隔离、早治疗。我国疫情总体得到控制，病死率得到有效控制。^[1,2,3,4]最近中国出现了零星的新冠肺炎病例。国家卫生健康委员会报告称，在2021年1月20日报告的本地传播病例中，黑龙江报告68例，吉林33例，河北20例，北京和山西各2例，山东1例。^[5]

作为一种新出现的急性呼吸道感染，2019冠状病毒病（COVID-19）已成为威胁全球健康的重大突发公共卫生事件。通过积极防控和救治措施，中方已基本控制住境内局势。该国部分地区仅存零星疫情和输入性病例。然而，由于病毒仍在全球蔓延，疫情可能会持续更长时间，COVID-19在中国重新出现的风险仍然存在。为了进一步遵守新冠肺炎患者的早期发现、报告、隔离和治疗原则，提高治愈率和降低病死率，我们更新了新冠肺炎患者诊疗方案（暂定第7版）通过总结我国近期临床经验，参考世界卫生组织等国家发布的治疗指南。因此，新冠肺炎患者诊疗方案（暂定第8版）被开发出来了。

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.