What to do next to control the 2019-nCoV epidemic?
2020; Elsevier BV; Volume: 395; Issue: 10222 Linguagem: Inglês
10.1016/s0140-6736(20)30300-7
ISSN1474-547X
Autores Tópico(s)COVID-19 Clinical Research Studies
ResumoThe 2019 novel coronavirus (2019-nCoV) infection can lead to acute resolved or fatal pneumonia. On the basis of knowledge of other coronaviruses, the main route of human-to-human transmission of 2019-nCoV is probably through respiratory droplets. As of Feb 4, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 20 438 confirmed cases, with 2788 (13·64%) patients in critical condition and 425 (2·08%) deaths; 23 214 additional suspected cases have also been identified so far. The most affected city, Wuhan, and related regions in Hubei province of China have reported 13 522 confirmed patients (66·16% of total cases) and 414 deaths from 2019 nCoV infection (97·41% of total deaths in China). 632 patients with confirmed infection have recovered and have been discharged from hospital. However, the downward turning point for new cases of infection has not been observed yet (figure). Notably, 159 confirmed cases have been reported in 23 other countries beyond China, including Japan, Thailand, Singapore, South Korea, Australia, the USA, Malaysia, and Germany. Because of the seriousness of this outbreak, WHO declared it a public health emergency of international concern on Jan 30, 2020, followed by the USA announcing a public health emergency on Jan 31, 2020. During the epidemic, rapid and robust research is important to help guide clinical practices and public health policies. Zhu and colleagues sampled bronchoalveolar-lavage fluid from three patients and used next-generation sequencing and PCR to characterise the virus, and they identified the pathogen of this outbreak as a novel coronavirus that falls within the subgenus Sarbecovirus of the genus Betacoronavirus and confirmed the cytopathic effects (structural changes in host cells) of this virus.1Zhu N Zhang D Wang W et al.A novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; (published online Jan 24.)DOI:10.1056/NEJMoa2001017Crossref PubMed Scopus (18596) Google Scholar Their achievement not only improves methods of diagnosis confirmation in clinics but also promotes the study of the underlying mechanisms of viral infection.2Zhou P Yang X Wang X et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; (published online Feb 3.)DOI:10.1038/s41586-020-2012-7Crossref Scopus (14414) Google Scholar Subsequently, collaborations between Chinese and international scientists have rapidly unmasked some additional virological features of 2019-nCoV. A specific viral nucleic acid assay using RT-PCR was quickly developed for the diagnosis of 2019-nCoV infection.3Corman VM Landt O Kaiser M et al.Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.Euro Surveill. 2020; 252000045Crossref PubMed Scopus (5023) Google Scholar, 4WHOLaboratory testing of human suspected cases of novel coronavirus (nCoV) infection: interim guidance, 10 January 2020. World Health Organization, Geneva2020Google Scholar Additionally, human angiotensin-converting enzyme 2 has been shown to be the putative receptor for the entry into host cells by use of bioinformatic prediction methods and in-vitro testing.2Zhou P Yang X Wang X et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; (published online Feb 3.)DOI:10.1038/s41586-020-2012-7Crossref Scopus (14414) Google Scholar, 5Xu X Chen P Wang J et al.Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission.Sci China Life Sci. 2020; (published online Jan 21.)DOI:10.1007/s11427-020-1637-5Crossref Scopus (1605) Google Scholar, 6Letko MC Munster V Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV.bioRxiv. 2020; (published online Jan 22.) (preprint)DOI: 10.1101/2020.01.22.915660Google Scholar Furthermore, bats are speculated to be the original host of this zoonotic virus, but whether an intermediate host facilitated the viral infection in humans is still unknown.7Lu R Zhao X Li J et al.Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.Lancet. 2020; (published online Jan 30)https://doi.org/10.1016/S0140-6736(20)30251-8Scopus (8216) Google Scholar Lastly, evidence of person-to-person transmission is accumulating,8Phan LT Nguyen TV Luong QC et al.Importation and human-to-human transmission of a novel coronavirus in Vietnam.N Engl J Med. 2020; (published online Jan 28.)DOI:10.1056/NEJMc2001272Crossref Scopus (811) Google Scholar, 9Chan JF Yuan S Kok KH et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30154-9Scopus (6200) Google Scholar with an estimated R0 of 2·2 (95% CI 1·4–3·9),10Li Q Guan X Wu P et al.Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia.N Engl J Med. 2020; (published online Jan 29.)DOI:10.1056/NEJMoa2001316Crossref Scopus (10671) Google Scholar and the assessment of the full extent of this mode of transmission is urgently needed. In The Lancet, two retrospective studies from Wuhan Jin Yin-tan Hospital have recently provided the first-hand evidence of epidemiological, clinical, laboratory, radiological imaging, and outcomes among 41 patients11Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Scopus (32878) Google Scholar and 99 patients.12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar Of 99 patients with 2019-nCoV pneumonia,12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar the average age was 55·5 years (SD 13·1) and 50 (51%) patients had chronic diseases. Clinical manifestations were fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). In view of the findings from both studies, as well as accumulated clinical experience, the next crucial step would be to identify the proper treatment for patients infected with 2019-nCoV. No fully proven and specific antiviral treatment for the coronavirus exists. Guidance from China's National Health Commission suggests taking an anti-HIV drug combination of lopinavir and ritonavir and inhaling a dose of nebulised interferon α for the antiviral therapy.13Chu CM Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.Thorax. 2004; 59: 252-256Crossref PubMed Scopus (1314) Google Scholar Many efforts, including several clinical trials, such as NCT04246242 and NCT04252664, are in progress to screen existing antiviral drugs to identify those that could be specific and efficient against 2019-nCoV. Notably, the first reported use of remdesivir, in the first diagnosed patient with 2019-nCoV infection in the USA,14Holshue ML DeBolt C Lindquist S et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; (published online Jan 31.)DOI:10.1056/NEJMoa2001191Crossref Scopus (4278) Google Scholar has encouraged additional clinical study of this medication. More importantly, patients in critical conditions often develop serious complications, such as acute respiratory distress syndrome (17 [17%] of 99 patients),12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar and thus medical groups should include physicians with expertise in both infectious diseases and critical care. It is noteworthy that patients in critical condition often show a reduction in peripheral blood lymphocytes.11Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Scopus (32878) Google Scholar, 12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar Whether immune cells infiltrate into the lungs and then cause serious lung lesions (as occurred in patients with severe acute respiratory syndrome [SARS])15de Wit E van Doremalen N Falzarano D Munster VJ SARS and MERS: recent insights into emerging coronaviruses.Nat Rev Microbiol. 2016; 14: 523-534Crossref PubMed Scopus (2394) Google Scholar is not clear. Therefore, it is important to understand the lung microenvironment and the map of immune responses against 2019-nCoV infection, which might help to define clinical stages and uncover the pathogenesis of the disease. Recent data showed that most deaths were due to respiratory failure;11Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Scopus (32878) Google Scholar, 12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar however, no reports of lung pathology in patients who died from 2019-nCoV infection have been reported so far. Notably, elderly men with 2019-nCoV infection and other underlying diseases often have a higher fatality rate than that of elderly women or younger and more healthy patients;11Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Scopus (32878) Google Scholar, 12Chen N Zhou M Dong X et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; (published online Jan 29)https://doi.org/10.1016/S0140-6736(20)30211-7Scopus (14366) Google Scholar more studies are needed to determine the associated influencing factors underlying this finding. The development of more efficient and quicker methods for the detection of viral nucleic acids is needed to ensure the accuracy of diagnosis. Several challenges remain for basic research, including viral mutation rate and transmission, infectivity dynamics, and viral infection-associated pathogenicity in vivo. Some evidence has suggested that the virus can spread during the incubation period9Chan JF Yuan S Kok KH et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30154-9Scopus (6200) Google Scholar, 16Rothe C Schunk M Sothmann P et al.Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.N Engl J Med. 2020; (published online Jan 30.)DOI:10.1056/NEJMc2001468Crossref Scopus (2813) Google Scholar and is detectable during the convalescent period.16Rothe C Schunk M Sothmann P et al.Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.N Engl J Med. 2020; (published online Jan 30.)DOI:10.1056/NEJMc2001468Crossref Scopus (2813) Google Scholar Notably, the virus was found in the loose stool of a patient in the USA,14Holshue ML DeBolt C Lindquist S et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; (published online Jan 31.)DOI:10.1056/NEJMoa2001191Crossref Scopus (4278) Google Scholar suggesting potential transmission through the faecal–oral route. It is of high priority to ascertain whether persistent asymptomatic carriers of 2019-nCoV exist and to reach an accurate definition of when a patient can be considered cured. Moreover, no certainty exists about the source of the outbreak, and a prophylactic vaccine is still under development. WHO has acknowledged the efforts made by the Chinese Government to investigate and contain the outbreak.17Wang W Tang J Wei F Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China.DOI: 10.1002/jmv.25689Google Scholar For example, authorities rapidly initiated the first measures to isolate Wuhan, which were then extended to the whole Hubei province, stranding 35 million residents during the heavy-travel Chinese Spring Festival holidays. At the same time, the two new-built hospitals in Wuhan have been put into use, with 2600 beds for the confirmed and suspected patients with pneumonia. The decision makers also extended the holiday period and postponed school openings. Additionally, at least 68 medical teams, including more than 8000 physicians and nurses, from other provinces and cities went to the most affected Hubei province to fight against the disease side by side with the local medical staff.18Huaxia68 medical teams sent to Hubei to aid coronavirus control. 2020.Xinhuanet. Feb 3, 2020; http://www.xinhuanet.com/english/2020-02/03/c_138752003.htmDate accessed: February 4, 2020Google Scholar The Chinese Government has initiated at least 13 research programmes as an emergency measure to study the different aspects of the outbreak such as the diagnosis, treatment, and prevention of 2019-nCoV-associated disease.19Ministry of Science and Technology of the People's Republic of ChinaEmergency scientific programs on prevention and control of the novel coronavirus-induced pneumonia.http://www.most.gov.cn/kjbgz/202001/t20200125_151233.htmDate: Jan 25, 2020Date accessed: February 4, 2020Google Scholar Novel therapeutic approaches, including treatment with allogeneic mesenchymal stem cells, are expected to progress to clinical trials involving patients with 2019-nCoV infection in a critical condition when the projects meet both ethical requirements and the principle of informed consent (eg, NCT04252118). Furthermore, therapeutic drugs, protective equipment, and charitable funds from inside and outside of China are transported to the epidemic area to support the response. All these measures are aimed to maximise prevention and minimise the occurrence of new infections, which will help the in-time diagnosis and treatment of patients and protect the healthy population against viral infection not only in China but also in the rest of the world. China also faces other challenges, including asymptomatic carriers with 2019-nCoV might be a new potential source of infection; there will be a huge increase in people returning from trips after the Chinese Spring Festival vacation; and it may be difficult to control the outbreak due to the lack of adequate medical resources in epidemic communities and rural areas of Hubei province. First-line medical staff and scientists in China have had a leading role in fighting the outbreak of 2019-nCoV-associated pneumonia. The basic and essential strategies that we should stick to remain the early detection, early diagnosis, early isolation, and early treatment of the disease. With the huge efforts from medical professionals to treat patients, substantial public health prevention measures, and accelerated research, we hope the downward turning points for both new cases of 2019-nCoV and the resulting fatal events might come soon. We declare no competing interests. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive studyThe 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Full-Text PDF Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Full-Text PDF
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