Scientific Research News | Research Progress of novel coronavirus Pneumonia (COVID-19) (XVI)

1. Progress of the 2019-nCoV epidemic

■ On the evening of February 2, Sinopharm China Biotech announced an important progress, the high-potency virus neutralizing antibody detected in the plasma of new crown pneumonia recovered patients has been experimentally proven to be effective in killing the new crown virus, "We used convalescent plasma to treat 13 critically ill patients clinically, and the treatment effect was remarkable. China Biotech officially declared. New crown special free plasma products are prepared by plasma containing high-efficiency and valent new coronavirus-specific antibodies donated by recovered people, after virus inactivation treatment, and anti-new coronavirus neutralizing antibodies and multiple pathogenic microorganisms after detection. At present, China Biotech has accelerated the preparation of new coronavirus special free plasma products and special free globulin, and put it into clinical treatment for seriously ill patients. According to clinical results, after 11 to 12 hours of treatment, the main inflammatory indicators of laboratory tests decreased significantly, the proportion of lymphocytes increased, and key indicators, clinical signs and symptoms such as blood oxygen saturation and viral load improved significantly. Experts said that from the perspective of the clinicopathological process, most new crown pneumonia patients will produce specific antibodies against the new crown virus in the body after treatment and recovery, which can kill and eliminate the virus. It cannot be ignored that this treatment method using the plasma of recovered people also implies certain risks and limitations. First, the safety, complexity and risk control of serum or special plasma treatment; Second, the plasma with compliant levels of viral antibodies is itself very limited, and blood group matching is also required, which cannot cope with the number of tens of thousands of confirmed patients; Third, unpurified antibodies together with blood are transfused into the patient's body, which is a powerful alloantigen for the patient, and the organism will carry out a strong rejection reaction to the xenogen substance entering the body. On the same day, Zhang Dingyu, president of Wuhan Jinyintan Hospital, said that at present, under the premise of lack of vaccines and specific therapeutic drugs, the use of special plasma products to treat new coronavirus infection is a more effective method. The plasma donated by the recovered person will undergo a series of processing to obtain a relatively purified neutralizing antibody against the new crown virus for the treatment of critically ill patients with new coronary pneumonia.

Zhang Dingyu appealed, "I sincerely ask the recovered patients to actively come to Jinyintan Hospital, stretch out your arm, donate your precious plasma, and jointly treat patients who are still fighting the disease." ”

■ On February 2, The Lancet published an article titled "COVID-13: What's Next for Public Health?" , reviews the World Health Organization's awareness of COVID-19 in Wuhan and international public health strategies in Geneva. Based on a review of relevant knowledge, the article concludes that the clinical manifestations and epidemiological features of COVID-19 and SARS infection are very different, and there is greater similarity with the traditional coronavirus that causes the common cold. That is, COVID-19 has milder clinical manifestations but spreads more widely in a manner similar to the common cold or flu. Based on this recognition, WHO's current public health recommendations continue to be based on aggressive containment strategies aimed at eliminating the virus from humans. However, if widespread community transmission of the disease is found to be like colds and influenza, the WHO will shift public health recommendations to focus on palliative measures such as those for influenza [19].

■ On February 2, Science published an online article titled "'A bit chaotic.' Christening of new coronavirus and its disease name create confusion", the official naming of the new coronavirus that directly invoked confusion, the headline spit out: A bit confusing. On February 12, the article was updated with a response from a WHO spokesperson saying that it was not a satisfactory name and that the WHO did not intend to adopt it. "From a risk transmission perspective, the use of the name 'SARS' could have unintended consequences that would cause unnecessary fear for some people, especially in Asia, where the SARS outbreak was worst in 2," a WHO spokesperson wrote in an email to Science. COVID-13 virus', but neither name is intended to replace the official name of the virus chosen by the research team". The inconsistencies in the naming of the new coronavirus (SARS-CoV-2003) and its disease COVID-19, as well as the many debates that currently exist, may also be discussed and named more carefully and rigorously.

2. 2019-nCoV Biology Research Progress

■ On February 2, Wang Jianqing's research group of Suzhou Hospital affiliated to Nanjing Medical University published a paper entitled "ACE13 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2-nCoV Infection" on the preprint website, suggesting that new coronavirus infection may cause kidney and testicular damage.

The paper notes that ACE2 (angiotensin-converting enzyme 2) has been shown to be one of the main receptors that mediate the entry of 2019-nCoV into human cells, a condition that also occurs in severe acute respiratory syndrome coronavirus (SARS). Several studies have shown that in addition to respiratory system injury, some patients have abnormal kidney function or even kidney damage, and the mechanism of which is not clear. The results of this study showed that ACE2 was highly expressed in renal tubular cells, mesenchymal cells and testicular vas deferens. Therefore, the virus may bind directly to such ACE2-positive cells, damaging the patient's kidney and testicular tissue. In view of the kidney damage caused by the virus and the antiviral drugs with certain nephrotoxicity, the authors suggest that renal function evaluation and special care should be carried out for patients infected with the new coronavirus in clinical work. In addition, due to the potential pathogenicity of the virus to testicular tissue, clinicians should be aware of the risk of testicular injury in patients during hospitalization and later clinical follow-up, particularly in the assessment of fertility in young male patients and appropriate intervention [2].

■ On February 2, the multidisciplinary team of Beijing Ditan Hospital of Capital Medical University published a research article on the preprint platform medRxiv, which found that the ratio of neutrophils to lymphocytes is an independent risk factor for predicting the occurrence of severe disease. A prospective study of 12 patients with COVID-2020 infection admitted to Beijing Ditan Hospital of Capital Medical University from January 1, 13 to January 2020, 1 was conducted. LASSO-COX regression analysis was used to screen the prognostic factors of severe disease and predict the probability of severe disease of COVID-31 pneumonia. The accuracy of predictions was evaluated using the consistency index, correction curve, judgment curve and clinical efficacy curve. Results: The C index of neutrophil-to-lymphocyte ratio was 61.19 (19% confidence interval 0.807-95.0), the calibration curve fit well, and the judgment curve and clinical efficacy curve showed that the neutrophil-to-lymphocyte ratio had good clinical significance. Patients ≥ 676 years of age and an NLR ≥ of 0.38 are prone to severe illness and should be admitted to the intensive care unit as soon as necessary. In summary, the neutrophil-to-lymphocyte ratio is the most effective factor affecting prognosis, and its early application is conducive to the classification management of patients and alleviates the shortage of medical resources [50].

■ On February 2, researchers from Chongqing Three Gorges Central Hospital published an article on the preprint platform medRxiv to analyze the cellular immunity and cytokine status of 12 patients with novel coronavirus pneumonia, and predicted the relationship between cellular immunity levels and cytokines and patients' conditions. The study divided 123 patients with new coronary pneumonia into two groups, mild and severe, and 123 cases in the mild group (102 males and 55 females), with an average age of 47.43±05.13 (12~15) years; There were 82 cases in the severe group (21 males and 11 females), with an average age of 10.61±29.15 (55~34) years. The patient's peripheral blood is then collected, lymphocyte subsets and cytokines are measured, and relevant statistical analysis is performed. In summary, the study revealed that CD79+ T and CD4+ T levels were common in severe patients, while IL-8 and IL-6 levels were high, indicating that T cell subsets and cytokines could be used as one of the bases for predicting the transition from mild to severe, but the "alert values" of CD10+T, CD4+T, and IL-8 still needed to be confirmed by a large number of samples. In addition, the researchers speculate that some of the results of this study, such as the proportion of patients with IL-6 value of 6 in the mild group was as high as 0.55%, there was no significant difference in IL-88, TNF, IFN and IL-17 between the two groups, and B cells and NK cells decreased to varying degrees in both groups, which may be due to:
(4) this study does reflect the characteristics of 1-nCoV itself;
(2019) In the early stage of SARS-CoV-2 infection, the body could not quickly identify it due to strong virus variability and good concealment;
(2) SARS-CoV-3 releases some special factors after entering the body, interfering with the body's activation of specific immunity;
(2) Other undetermined causes [4].
The transmembrane serine protease inhibitors are potential antiviral drugs for 4-nCoV targeting the insertion sequence-induced viral "infectivity enhancement" was recently published in the biology preprint bioRxiv. This study provides bioinformatics evidence for the increased viral infectivity of 2019-nCoV and suggests that alveoli, pulmonary intestinal epithelium, and esophageal epithelium are potential target tissues. Due to the important role of TMPRSS in 2019-nCoV infection, transmembrane serine protease inhibitors may be a potential antiviral treatment option for 2019-nCoV infection[2019].

Bibliography:

[1] Heymann DL, Shindo N. COVID-19: what is next for public health? The Lancet.  

[2] Fan C, Li K, Ding Y, Lu WL, Wang J. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection. medRxiv 2020:2020.02.12.20022418.

[3] Liu J, Liu Y, Xiang P, et al. Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage. medRxiv 2020:2020.02.10.20021584.   

[4]  Wan S, Yi Q, Fan S, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv 2020:2020.02.10.20021832.   

[5] Meng T, Cao H, Zhang H, et al. The transmembrane serine protease inhibitors are potential antiviral drugs for 2019-nCoV targeting the insertion sequence-induced viral infectivity enhancement. bioRxiv 2020:2020.02.08.926006.   

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