Feb 24, 2020 — not yet affected. The major objectives of the Joint Mission were as follows: • To enhance understanding of the evolving COVID-19 outbreak in
40 pages
Missing: podía | Must include: podía
22 KB – 40 Pages
PAGE – 2 ============
2 Table of Contents I. THE MISSION 3 G OAL AND O BJECTIVES 3 M EMBERS & M ETH OD OF W ORK 3 II. MAJOR FINDINGS 4 T HE VIRUS 4 T HE OUTBREAK 5 T HE TRANSMISSION DYNA MICS 9 T HE SIGNS , SYMPTOMS , DISEASE PROGRESSION AND SEVERITY 11 T HE C HINA RESPONSE 14 K NOWLEDGE GAPS 16 III. ASSESSMENT 16 T HE C HINA R ESPONSE & N EXT S TEPS 16 T H E G LOBAL R ESPONSE & N EXT S TEPS 18 IV. MAJOR RECOMMENDATION S 21 F OR C HINA 21 F OR COUNTRIES WITH IM PORTED CASES AND / OR OUTBREAKS OF COVID – 19 21 F OR UNINFECTED COUNTR IES 22 F OR THE PUBLIC 22 F OR THE INTERNATIONAL COMMUNITY 23 ANNEXES 24 A. WHO – C HINA J OINT M ISSION M EMBERS 24 B. S UMMARY A GENDA OF THE M ISSION 25 C. D ETAILED T ECHNICAL F INDINGS 27 R ESPONSE MANAGEMENT , CASE AND CONTACT MA NAGEMENT , RISK COMMUNICATION AND COMMUNITY ENGAGEMENT 27 C LINICAL CASE MANAGEM ENT AND INFECTION PR EVENTION AND CONTROL 31 L ABORATORY , DIAGNOSTICS AND VIR OLOGY 33 R ESEARCH & D EVELOPMENT 34 D. K NOWLEDGE G APS 36 E. O PERATIONAL & T ECHNICAL R ECOMMENDATIONS 38
PAGE – 3 ============
3 I. The Mission Goal and Objectives The overall goal of the Joint Mission was to rapidly inform national (China) and international planning on next steps in the response to the ongoing outbreak of the novel coronavirus disease ( COVID – 19 1 ) and on next steps in re a diness and pr eparedness for geographic areas not yet affected. The major objectives o f the Joint Mission we re as follows: To enhance understanding of the evolving COVID – 19 outbreak in China and the nature and impact of ongoing containment measures; To share knowledge on COVID – 19 response and preparedness measures being implemented in countries affected by or at risk of importations of COVID – 19 ; To generate recommendations for adjusting COVID – 19 containment and response measures in China and internati onally; and To establish priorities for a collaborative programme of work , research and development to address critical gaps in knowledge and response and readiness tools and activities. Members & Method of Work The Joint Mission consisted of 25 national and international experts from China, Germany, Japan, Korea, Nigeria, Russia, Singapore, the United States of America and the World Health Organization (WHO) . The Joint Mission was headed by Dr Bruce Aylward of WHO and Dr Wannian ublic of China. The full list of members and their affiliations is available in Annex A . The Joint Mission was implemented over a 9 – day period from 16 – 2 4 February 2020 . The schedule of work is available in Annex B . The Joint Mission began with a detaile d workshop with representatives of all of the principal ministries that are leading and/or contributing to the response in China through the National Prevention and Control Task Force. A series of in – depth meetings were then conducted with national level institutions responsible for the management, implementation and evaluation of the response, particularly the National Health Commission and the China Center s for Disease Control and Prevention (C hina CDC) . To gain first – hand knowledge on the field level implementation and impact of the national and local response strategy, under a range of epidemiologic and provincial contexts, visits were conducted to Beijing Municipality and the provinces of Sichuan (Ch engdu), Guangdong (Guangzhou, Shenzhen) and Hubei (Wuhan). The field visits included community centers and health clinics, country/district hospitals, COVID – 19 designated hospitals, transportations hubs (air, rail, road), a wet market, pharmaceutical and personal protective equipment ( PPE ) stocks warehouses , research institutions, provincial health commissions, and local Centers for 1 In the Chinese version of this report, COVID – 19 is referred to throughout as novel coronavirus pneumonia or NCP, the term by which COVID – 19 is most widely known in the
PAGE – 4 ============
4 Disease Control (provincial and prefecture) . During these visits, the team had detailed discussion and consultations with Pr ovincial Governors, municipal Mayors, their emergency operations teams, senior scientists, frontline clinical , public health and community workers , and community neighbourhood administrators . The Joint Mission concluded with working sessions to consolidat e findings, generate conclusions and propose suggested actions. To achieve its goal, the Joint Mission gave particular focus to addressing key questions related to the natural history and severity of COVID – 19, the transmission dynamics of the COVID – 19 viru s in different settings, and the impact of ongoing response measures in areas of high (community level), moderate (clusters) and low (sporadic cases or no cases ) transmission. The findings in review of national and local governmental reports, discussions on control and prevention measures with national and local experts and response teams, and observations made and insights gained during site visits . The figures have been produced using information and data coll ected during site visits and with the agreement of the relevant groups . R eferences are available for any information in this report that ha s already been published in journals . The final report of the Joint Mission was submitted on 2 8 February 2020. II. Major findings The major findings are described in six sections: the virus, the outbreak, transmission dynamics , disease progression and severity , the China response and knowledge gaps. More detailed descriptions of technical findings are provided in An nex C. The virus On 30 Dec ember 2019, three bronchoalveolar lavage samples were collected from a patient with pneumonia of unknown etiology a surveillance definition established following the SARS outbreak of 2002 – 2003 in Wuhan Jinyintan Hospital . R eal – time PCR (RT – PCR) assay s on these samples were positive for pan – Betacoronavirus. Using Illumina and nanopore sequencing , the whole genome sequences of the virus were acquired. Bioinf or matic analys e s indicated that the virus had features typical of the coronavirus family and belong ed to the Betacoronavirus 2B lineage. Alignment of the full – length genome sequence of the COVID – 19 virus and other available genomes of Betacoronavirus showed the closest relationship was with the b at SARS – like coronavirus strain BatCov RaTG13 , identity 96%. Virus isolation was conduct ed with various cell lines, such as human airway epithelial cells, Vero E6, and Huh – 7. Cytopathic effects (CPE) were observed 96 hours after inoculation. Typical crown – like particles were obs erved under transmission electron microscope (TEM) with negative staining. The cellular infectivity of the isolated viruses could be completely neutralized by the sera collected from convalescent patients. Transgenic human ACE2 mice and Rhesus monkey int ranasally challenged by this virus isolate induced multifocal pneumonia with interstitial hyperplasia . T he COVID – 19 virus w as subsequently detected and isolated in the lung and intestinal tissues of the challenged animals.
PAGE – 5 ============
5 Whole genome sequencing analy sis of 104 strains of the COVID – 19 virus isolated from patients in different localities with symptom onset between the end of Dec ember 2019 and mid – Feb ruary 2020 showed 99.9% homology, without significant mutation (Figure 1) . F igure 1. Phylogenetic analysis of the COVID – 19 virus and its closely related reference genomes Note: COVID – 19 virus is referred to as 2019 – nCoV in the figure, the interim virus name WHO announced early in the outbreak. Post – mortem samples from a 50 – year old male patient from Wuha n were taken from the lung, liver, and heart. Histological examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates. The lung showed evident desquamation of pneumocytes and hyaline membrane formation, indicating acute respiratory distress syndrome (ARDS). Lung tissue also displayed cellular and fibromyxoi d exudat ion, desquamation of pneumocy tes and pulmonary oedema . In terstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in both lungs. Multinucleated syncytial cells with atypical enlarged pneumocytes characterized by large nuclei, amphophilic granular cytoplasm, and prominent nucleoli wer e identified in the intra – alveolar spaces, showing viral cytopathic – like changes. No obvious intranuclear or intracytoplasmic viral inclusions were identified. The outbreak As of 2 0 February 2020 , a cumulative total of 7 5 , 465 COVID – 19 case s were reported in China . Reported cases are based on the National Reporting System (NRS) between the
PAGE – 6 ============
6 National and Provincial Health Commissions. The NRS issues daily reports of newly recorded confirmed cases, deaths, suspect ed cases, and contacts. A daily repo rt is provided by each province at 0300hr in which they report cases from the previous day. The epidemic curves presented in Figures 2 and 3 Infectious Disease Information System (IDIS), which requires each COVID – 19 case to be reported electronically by the responsible doctor as soon as a case has been diagnosed. It includes cases that are reported as asymptomatic and data are updated in real time. Individual case reporting forms are downloaded after 2400hr daily . Epidemiologic curves for Wuhan, Hubei (outside of Wuhan), China (outside Hubei) and China by symptom onset are provided in Figure 2. Figure 2 Epidemiologic curve of COVID – 19 laboratory confirmed c ases , by date of onset of illness, reported in China , as of 2 0 February 2020
PAGE – 8 ============
8 Demographic characteristics Among 5 5 ,924 laboratory confirmed cases reported as of 20 February 2020 , the median age is 51 years (range 2 days – 100 years old ; IQR 39 – 63 years old ) with the majority of cases ( 77.8% ) aged between 30 69 years . Among reported cases, 51. 1 % are male, 77. 0 % are from Hubei and 2 1.6 % are farmers or laborer s by occupation . Zoonotic origins COVID – 19 is a zoonotic virus. From phylogenetics analyses undertaken with available full genome sequences , bats appear to be the reservoir of COVID – 19 virus , but t he intermediate host(s) has not yet been identified . However, t hree important areas of work are already underway in China to inform our understanding of the zoonotic origin of this outbreak. These include early investigations of cases with symptom onset in Wuhan throughout December 2019, environmental samp ling from the Huanan Wholesale Seafood M arket and other area markets , and the collection of detailed records o n t he source and type of wildlife species sold at the Huanan market and the destination of th ose animals after the market was closed . Routes of transmission COVID – 19 is transmitted via droplet s and fomites during close unprotected contact between an infector and infectee . Airborne spread has not been reported for COVID – 19 and it is not believed to be a major driver of transmission based on available evidence ; however, it can be envis a ged i f certain aerosol – generating procedures are conducted in healt h care facilities . Fecal shedding has been demonstrated from some patients , and viable virus has been identified in a limited number of case reports . However, the fecal – oral route does not appear to be a driver of COVID – 19 transmission ; its role and sign ificance for COVID – 19 remains to be determined. Viral shedding is discussed in the Technical Findings (Annex C) . Household transmission In China, h uman – to – human t ransmission of the COVID – 19 virus is largely occurring in families. T he Joint M ission received detailed information from the investigation of clusters and some household transmission studies , which are ongoing in a number of Provinces . Among 344 clusters involving 1308 cases (out of a total 1836 cases reported) in Guangdong Provinc e and Si chuan Province , most clusters ( 78% – 85 %) have occurred in famil ies. Household transmission studies are currently underway, but preliminary studies ongoing in Guangdong estimate the secondary attack rate in household s ranges from 3 – 10%. Contact Tracing Chi na has a policy of meticulous case and contact identification for COVID – 19. For example, i n Wuhan more than 18 00 teams of epidemiologists , with a minimum of 5 people/team, are tracing tens of thousands of contacts a day. Contact follow up is painstaking , with a high percentage of identified close contacts complet ing medical observation . Between 1 % and 5% of contacts were subsequently laboratory confirmed cases of COVID – 19 , depending on location . For example: As of 17 February , in Shenzhen City, among 2 842 identified close contacts, 2842 ( 100 %) were traced and 2240 (72%) have completed medical observation . Among the close contacts , 88 (2.8%) were found to be infected with COVID – 19 .
PAGE – 9 ============
9 As of 17 Feb ruary , in Sichuan Province, among 25493 identified close con tacts, 25347 (99%) were traced and 23178 (91%) have completed medical observation . Among the close contacts, 0.9% were found to be infected with COVID – 19 . As of 20 February , in Guangdong Province, among 9939 identified close contacts, 9939 (100%) were tr aced and 7765 (78%) have completed medical observation . Among the close contacts, 479 (4.8%) were found to be infected with COVID – 19 . Testing at fever clinics and from routine ILI/SARI surveillance The Joint Mission systematically enquired about testing for COVID – 19 from routine respiratory disease surveillance systems to explore if COVID – 19 is circulating more broadly and undetected in the community in China . These systems could includ e RT – PCR testing of COVID – 19 virus in influenz a – like – illness (ILI) and sever e acute respiratory infection (SARI) surveillance systems , as well as testing of results among all visit ors to fever clinics. In Wuhan, COVID – 19 testing of ILI samples (20 per week) in November and December 2019 and in the fi rst two weeks of January 2020 found no positive results in the 2019 samples, 1 adult positive in the first week of Ja nuary , and 3 adults positive in the second week of January; all children tested were negative for COVID – 19 although a number were positive for influenza . In Guangdong, from 1 – 14 January, only 1 of more than 15000 ILI/SARI samples tested positive for the COVID – 19 virus . In one hospital in Beijing, there were no COVID – 19 positive samples among 1910 collected from 28 January 2019 to 13 Februar y 2020 . In a hospital in Shenz h en, 0/40 ILI samples were positive for COVID – 19. Withi n the f ever clinics in Guangdong , the percent age of samples that tested positive for the COVID – 19 virus has decreased over time from a peak of 0 .47 % positive on 30 January to 0.0 2 % on 16 February. Overall in Guangdong, 0.14% of approximately 3 2 0,000 fever clinic screenings were positive for COVID – 19. Susceptibility As COVID – 19 is a newly identified pathogen, there is no known pre – existing immunity in humans. B ased on the epidemiologic characteristics observed so far in China , everyone is assumed to be susceptible, although there may be risk factors increasing susceptibility to infection . This requires further study, as well as to know whether ther e is neutralising immunity after infection. The t ransmission dynamics Inferring from Figures 2 and 3 , and based on our observations at the national and provincial/municipal levels during the Joint Mission, we summarize and interpret the transmission dynamics of COVID – 19 thus far. It is important to note that t ransmission dynamics of any outbreak are inherently contextual. For COVID – 19, we observe four major types of transmission dynamics during t he epidemic growth phase and in the post – control period , and highlight what is known about transmission in children , as follows:
PAGE – 10 ============
10 Transmission in Wuhan E arly cases identified in Wuhan are believed to be have acquired infection from a zoonotic source as ma ny reported visiting or working in the Huanan Wholesale Seafood Market . As of 25 February, an animal source has not yet been identified. At some point early in the outbreak, some cases generated human – to – human transmission chains that seeded the subsequ ent community outbreak prior to the implementation of the comprehensive control measures that were rolled out in Wuhan . The dynamics likely approximated mass action and radiated from Wuhan to other parts of Hubei province and China , which explains a relatively high R 0 of 2 – 2.5 . The cordon sanitaire around Wuhan and neighboring municipalitie s imposed since 23 January 2020 has effectively prevented further exportation of infected individuals to the rest of the country. Transmission in Hubei, other than Wuhan In the prefectures immediately adjoining Wuhan (Xiaogan, Huanggang, Jingzhou and Ezhou), transmission is less intense . For other prefectures, due to fewer transport links and human mobility flows with Wuhan, the dynamics are mor e closely aligned with those observed in the other areas of the country. Within Hubei, the implementation of control measures (including social distancing) has reduced the community force of infection, resulting in the progressively lower incident reporte d case counts. Transmission in China outside of Hubei G population movement during the Chinese New Year ( chunyun ) , infected individuals quickly spread throughout the country, and were particularly concentrated in cities with the highest volume of traffic with Wuhan. Some of these imported seeds generated limited human – to – human transmission chains at their destinatio n . Given the Wuhan/Hubei experience, a comprehensive set of interventions, including aggressive case and contact identification, isolation and management and extreme social distancing, have been implemented to interrupt the chains of transmission nationwide. To date, m ost of the recorded cases were imported from or had direct links to Wuhan/Hubei. Community transmission has been very limited. Most locally gen erated cases have been clustered, the majority of which have occurred in households , as summarized above . Of note, the highly clustered nature of local transmission may explain a relatively high R 0 (2 – 2.5) in the absence of interventions and low confirme d case counts with intense quarantine and social distancing measures. Special settings We note that instances of transmission have occurred within health care settings prisons and other closed settings . A t the pres e nt time, it is not clear what role these settings and groups play in transmission. However, t hey do not appear to be major drivers of the overall epidemic dynamics. Specifically , we note :
PAGE – 11 ============
11 (a) Transmission in h ealth care settings and among health care workers (HCW) The Joint Mission discussed nosocomial infection in all locations visited during the Mission. As of 20 February 2020 , t here were 2,055 COVID – 19 laboratory – confirmed cases reported among HCW from 476 hospitals across China. The majority of HCW cases ( 88 %) were reported from Hubei. Remarkably, m ore than 40,000 HCW have been deployed from other areas of China to support the response in Wuhan . N otwithstanding discrete and limited instances of nosocomial outbreaks (e . g . a nosocomial outbreak involving 15 HCW in Wuhan), transmission within health care settings and amongst health care workers does not appear to be a major transmission feature of COVID – 19 in Chin a. The Joint Mission learned that, among the HCW infections, most were identified early in the ou tbreak in Wuhan when supplies and experience with the new disease was lower. Additionally, investigations among HCW suggest that many may have been infected within the household rather than in a health care s e tting. Outside of Hubei, health care worker infections have been less frequent ( i. e. 246 of the total 2055 HCW cases ). W hen exposure was investigated in these limited cases, the exposure for most was reported to have be en traced back to a confirmed case in a hou sehold . The Joint Team noted th at attention to the prevention of infection in health care worker s is of paramount importance in China . Surveillance among health care workers identified factors early in the outbreak that placed HCW at higher risk of infection, and this information has been used to modify policies to improve protect ion of HCW . (b) Transmission in c losed settings T here have been reports of COVID – 19 transmission in prisons (Hubei, Shandong, and Zhejiang, China ), hospitals (as ab ove) and in a long – term living facility . The close proximity and contact among people in these settings and the potential for environmental contamination are important factors , which could amplify transmission . Transmission in these settings warrants further study. Children Data o n individuals aged 1 8 years old and under suggest that there is a relatively low attack rate in this age group (2.4% of all reported cases). Within Wuhan, among testing of ILI samples , no children were positive in November a nd December of 2019 and in the first two weeks of January 2020 . From available data , and in the absence of results from serologic studies, it is not possible to determine the extent of infection among children, what role children play in transmission, whether children are less susceptible or if they present differently clinically (i.e. generally milder presentations). T he Joint Mission learned that infected children have largely been identified through contact tracing in households of adults . Of note , people interviewed by the Joint Mission T eam could not recall episodes in which transmission occurred from a child to an adult. The s igns, s ymptoms , disease progression and s everity Symptoms of COVID – 19 are non – specific and the disease presentation can range from no symptoms (asymptomatic) to severe pneumonia and death. As of 20 February 2020 and
22 KB – 40 Pages