2019 Novel Coronavirus Global Research and

Innovation Forum:
Towards a Research Roadmap

Pr. Yazdan Yazdanpanah, Chair of GloPID R

https://www.glopid-r.org @GloPID_R
Background
• WHO’s R&D Blueprint has been
activated since early January 2020,
providing transparent and coordinated
information sharing on research starting
before the causal agent was identified.
• R&D Blueprint works closely with
GLOPID-R
 Background
• GLOPID-R an international network
of research funding organizations
28 Members and 2 observers
“facilitate, accelerate and deepen
collaboration among research funders on
emerging diseases”:
• to strengthen global research
preparedness between crises.
• to respond rapidly and effectively to
significant infectious disease outbreaks.
 Background
• Many unknowns including:
➢ disease and its optimal management
➢ virus reservoirs (the origin?)
➢ virus evolution
➢ transmission and epidemiology
• Urgent need to develop safe and effective
countermeasures that can be available, accessible
and suitable for use in populations most in need
Research is an important integral component
of the response
 5

Global research response: multi-

sectoral and interdisciplinary with
cross-border collaborations;
partnerships across professional disciplines,
across sectors and across borders
 Global international research: core concepts

• Focus: Have common goals and minimum common program

• Values: Understand others organizational culture & underlying societal
norms
• Equity: Mutual respect and openness
• Benefit: Communities and/or organizations
• Communication: open, honest and unambiguous
• Leadership: development and careful planning

Larkan et al. Globalization and Health (2016)

 7

Datasharing to:
• reduce the duplication of work
• provide a clearer picture of epidemiology and
pathology

Principles for datasharing: Timely – Ethical – Accessible

– Transparent – Equitable – Fairness - Quality
 Meeting Purpose
• To enable identification of key knowledge
gaps and research priorities, and thereby
accelerate the generation of critical
scientific information and the most needed
medical products to contribute to the control
the 2019-nCoV emergency.

With researchers from multiple specialties, funders,

public health, regulatory experts, ethicists
 Expected Outcome
• A research roadmap with clearly defined
priorities and governance framework
addressing all of the thematic areas
outlined in the agenda
 Format
• Review of epidemiological situation, and
overviews of each thematic area this
morning
• Parallel sessions this afternoon
• Tomorrow:
• Developing a coherent research
roadmap
• Governance Framework
 Note confidential data may be presented
• And confidentiality of such data must be
respected
• All those taking part whether in person or
remotely must have signed the
confidentiality agreement
Lassa epidemic in Nigeria

CCHF epidemic in Mali Ebola epidemic in DRC

Thank you

Together, we can make a difference for those

suffering from or at risk of 2019-nCoV infection
Update on 2019-nCoV

11 February 2020

HEALTH
EMERGENCIES
programme
Evolution of the 2019-nCoV outbreak (31 December 2019 – 10 February 2020)
Dec 31, 2019
Cluster of 27 pneumonia Jan 29, 2020
cases of unknown origin with 7 First confirmed cases in
severe cases reported to China UAE, Finland and Italy
Jan 11, 2020 Jan 30, 2020
National Health Commission Feb 5, 2020
First fatal case in China
Press
Jan 28, 2020 2nd Emergency
Jan 19, 2020 Release by
Jan 7, 2020 First confirmed case Committee – WHO
First confirmed Japanese
Novel coronavirus Jan 23, 2020 in declares a PHEIC
case in government
isolated First confirmed Germany
Republic of about 10
Jan 13, 2020 case in Singapore Jan 26, 2020 First confirmed cases in
Korea cases on
First First confirmed India and Philippines
cruise ship
confirmed Shutdown of case in Canada
case in Wuhan City
Nepal

Jan 31, 2020

Jan 8, 2020 Jan 14, 2020 Jan 25, Feb 4, 2020
First confirmed
First confirmed First 2020 First
Jan 22-23, 2020 cases in Russian
case in confirmed First confirmed
1st Emergency Federation,
Thailand case in confirmed Feb 1, case in
Committee Spain, Sweden
Japan cases in 2020 Belgium
Jan 20, 2020 and UK
Jan 1, 2020 Australia Index case
Infection in health-care workers
Huanan Seafood Wholesale and on Princess
caring for 2019-nCoV Jan 27, 2020
market closed Malaysia Diamond Feb 2,
Patients First confirmed cases in
Jan 24, 2020 cruise ship 2020
Jan 12, 2020 Cambodia and Sri Lanka
First confirmed confirmed First fatal
Named as 2019-nCoV; First confirmed case in USA
cases in France in Hong case
Whole genome sequence WHO Director General in
and Viet Nam Kong SAR outside
shared with WHO China confirms human to human China China
transmission HEALTH
EMERGENCIES HEALTH

EMERGENCIES
programme
programme
Current Situation (as of 11 Feb, 6am Geneva time)
Between 31 Dec 2019 - 11 Feb 2020
Updates from last 24 hours In total, 43,101 confirmed cases including 1,018
deaths globally
China:
– 2,484 new confirmed cases: 84%, 2,097 cases from Hubei China
– 849 new severe cases and 108 deaths: Hubei(103), – 42,708 confirmed cases
Beijing(1), Tianjin(1), Heilongjiang(1), Anhui(1), Henan(1)) – 7,333 severe cases
– 3,536 new suspected cases – 1,017 deaths: Hubei(974), Heilongjiang(8), Henan(7),
Anhui(4), Beijing(3), Hainan(3), Tianjin(2), Hebei(2),
Chongqing(2), Gansu(2), Jilin(1), Shanghai(1), Jiangxi(1),
Outside China: Shandong(1), Hunan(1), Guangdong(1), Guangxi(1),
– 74 new confirmed cases: International conveyance Sichuan(1), Guizhou(1), Hong Kong SAR(1)
(Japan)(65), The United Kingdom(4), Singapore(2), Viet
Nam(1), United Arab Emirates(1), Republic of Korea(1)
Outside China
– 393 cases from 24 countries
– 1 death

HEALTH
EMERGENCIES
programme
HEALTH
EMERGENCIES
programme
Number of confirmed cases in China by day of report (Hubei vs. Other
Provinces)

HEALTH
EMERGENCIES
programme
Number of reported confirmed and suspected cases in China by day of
report

HEALTH
EMERGENCIES
programme
Number of Cases of 2019-nCoV Reported Outside of China
As of 10 February

Confirmed cases of 2019-nCoV identified outside of China, by Confirmed cases of 2019-nCoV identified outside of China, by
date of reporting and travel history (n=319) date of onset of symptoms and travel history (n=144)*

*16/319 cases detected while asymptomatic; Information on date of onset not

available for remaining cases

HEALTH
EMERGENCIES
programme
Severity of disease among reported 2019-nCoV patients

• Patients present with fever, cough, shortness of breath, myalgia, confusion, headache
• Severity ranges from mild to severe disease resulting in death
– As of 10 Feb 7,333 patients reported as severe (17%) and an additional 1,018 people (2%) have died

• Fatal cases in China strongly associated with older age (>60 years old); comorbidities common in older patients, may not
be an independent risk factor
– Cause of death due to progressive respiratory and multi-organ failure
– Most deaths occur after prolonged course (7-10 days)
– 55% of the patients reported as severe have recovered

• True case-fatality ratio difficult to assess, denominator (number of infections) unknown

21
HEALTH
EMERGENCIES
programme
Transmission features

• 2019-nCoV is a zoonotic virus; supported by:

– Epidemiologic evidence of exposures of some initial cases
– Results of environmental sampling in Huanan Seafood and live animal market
– Early phylogenetic results suggest initial human infection in Nov 2019 followed by
ongoing human-to-human transmission
54 full genomes available
– Animal source not yet identified; spillover events could continue

• Human-to-human transmission
– Transmission via droplet, contact, fomites
• Occurring amongst close contacts, including family members and HCWs
• 1 example of health-care associated outbreak in Wuhan (involving 15 HCW), HCW infections in other cities in China, in France
• Detailed exposure histories and investigations are needed to understand frequency and significance of transmission from asymptomatic PCR
positive people; not known to be drivers of transmission for other coronaviruses
– Transmission parameter estimates
• Estimates of R0 ranging from 1.4-4.9 in China
• Incubation period estimated range 1-12.5 days, median 5-6 days (WHO guidance includes 14 days) HEALTH
EMERGENCIES
• Limited H2H transmission in 10 countries outside of China programme
 WHO Risk Assessment

• Potential impact to human health

– Can causes severe disease and fatalities
– Severity is not fully understood
• Likelihood of spread – Transmission from asymptomatic cases
– Ongoing human-to-human transmission
– Confirmed identified in 31 provincial level administrative areas • Likelihood of insufficient control capacities
(10 with >100 cases)
– China has implemented major control measures
– Majority of cases exported outside China have been
– Currently affected countries have strong public health systems
epidemiologically linked to Wuhan
– Some countries may be less prepared to manage cases
– Human-to-human transmission documented in other
countries
– Source of outbreak remains unknown
– Disaggregated data is needed to better understand the
epidemiology
23
HEALTH
EMERGENCIES
programme
Priorities for stopping transmission and mitigating the impact of 2019-nCoV globally

• Limit human-to-human transmission WHO technical guidance to support countries

– Reduce secondary infections among close contacts and health care workers Surveillance and case definitions
– Prevent transmission amplification and super spreading events Laboratory testing
Clinical management
– Prevent further international spread Infection prevention and control
• Identify, isolate and care for patients early Home care
Risk communication & community engagement
– Equip countries to detect, isolate and care for infected patients
Country readiness
– Provide optimized care Disease commodity package
• Reduce transmission from animal source Reducing risk of transmission from animals
Use of masks
– Identify animal source(s) and limit exposure
• Address critical unknowns
– Clinical severity, extent of transmission and infection, treatment options, diagnostics, therapeutics and vaccines
• Communicate critical risk and event information to all communities & counter misinformation
• Minimize social and economic impact through multisectoral partnerships

HEALTH

https://www.who.int/health-topics/coronavirus EMERGENCIES
programme
Strategic response plan: Accelerating priority research and innovation

• Address crucial unknowns regarding clinical severity extent of

transmission and infection, treatment options
• Enhance global coordination of all relevant R&D stakeholders
through existing mechanisms
• Support a clear and transparent global research and
innovation priority setting process
• Build common platforms for standardized processes,
protocols and tools, as well as for sharing specimens, data,
and information

HEALTH
EMERGENCIES
programme
2019 novel Coronavirus
Global research and innovation
forum: towards a research roadmap
Overview of state of the art and outline of key
knowledge gaps

• State of the art

• Knowledge gaps
• Ongoing research efforts
Overview of state of the art and outline of key
knowledge gaps – State of the art
• In-house RT-PCR detection in place, deployment ongoing (current focus:
Africa)
• Ready-to-use formulations on research use only basis available, in vitro
diagnostic-qualified products in the pipeline
• Virus isolation capacities available in reference centers
• Generic sequencing capacities widely available
• Virus isolates available under minimal material transfer agreements

• In all of these provisions: severe bottlenecks in logistics

Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps: clinical
virus detection
• Compartments of replication
• Prognostic information from viral load or viral load trajectories
• Prognostic information from immuno-markers
• Infectivity surrogates, discharge criteria

• Treatment-related monitoring
• Escape mutants (in-vitro, empirical)
• Geno-to-pheno approaches

• Phenotypic change (geno to pheno)

• Diagnostic drift: PCR assay compatibility changing over time
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps: immunity
and immune diagnostics
• Strength and duration of immunity
• Influence of pre-existing immunity against heterologous human coronaviruses

• Reflection of immunity by antibody tests

• Reflection of immunity by cell-level surrogates (Elispot etc.)
• Utiliy of innate immunity testing in patients
• Value of advanced affinity assays (e.g., whole proteome arrays)

• Sero-specificity and costimulation in serological diagnostics

• Technical gaps: simple IFA, differential IFA, ELISA, Neutralization assays, Neutralization
assay surrogates including pseudotypes and competitive ELISA
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps: tools for
infection control
• Virus stability (physical, chemical inactivation)
• Surrogate viruses for stability studies (BCoV, MHV, etc.)
• Infectivity of RNA

• Technical gaps: Infectivity assays (cell culture models, animal models); point of care
tests
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps: clinical
processes

• High throughput and automation of PCR detection

• Point of care testing
• Respiratory pathogens multiplex detection
• Devices related to prognostic markers
• Digital solutions for field lab assistance

• Bedside and lab-based sequencing approaches

Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts

• Descriptive patient-centered studies based on individual cases or opportunity-

driven cohorts

• Implementation-related work
• Validation of in-house protocols
• Validation of kits
• Logistics
• Reference laboratory services

• Provision of virus and reference material (European Virus Archive-Global)

Overview of state of the art and outline of key
knowledge gaps – Conclusions

Key areas of focus/considerations for research on the virus

1. What is the location and duration of viral replication and shedding; what are implications for
clinical management?
2. How best to characterize transmissibility and infectivity in laboratory environments?
3. What is the role of ongoing genome sequencing for outbreak management and
development/monitoring of countermeasures
4. What are the key uses for immunodiagnostics/serology
5. How do we maximize impact of research in this area taking into account timeframes and
feasibility?
Overview of state of the art and outline of key
knowledge gaps
• State of the art
• Knowledge gaps
• Ongoing research efforts

Thematic area 2

Animal and environmental research on the virus

origin, and management measures at the human-
animal interface
Overview of state of the art and outline of key
knowledge gaps – State of the art
• 2019-nCoV 96.2% full genome identity with a clade 2b β-CoV from Rhinolophus
affinis bat in Yunnan, China.
• All clade 2b CoVs found in bats (exc. SARS-CoV which may have evolved from a
bat SARSr-CoV via interm hosts)
• Rhinolophus spp. abundant & diverse in S. China, and across Asia, the Middle
East, Africa and Europe.
• >500 CoVs identified in bats in China, incl. SADS-CoV, SARSr-CoVs. Estimates of
likely unknown CoV diversity in bats reach >5,000
• Southwest China and neighboring countries: likely center of evolutionary
diversification of clade 2b CoVs (Latinne et al. in review).
Overview of state of the art and outline of key
knowledge gaps – State of the art
• High proportion of 1st & 2nd gen. human cases to the Huanan Seafood Wholesale
Market in Wuhan.
• Route of spillover from bats to humans unclear, and may involve domesticated
mammals, farmed or hunted wildlife (e.g. civets, cf. SARS-CoV)
• Bats are rare in markets in S. China, but hunted widely and sold directly to
restaurants for food (Li et al. 2019)
• 2.9% bat-CoV seroprevalence in small sample of rural Yunnan people: non-market
exposure to bat-CoVs is common (Wang et al. 2018).
• Extrapolation of human seroprevalence across Rhinolophus spp. hotspots in SE Asia:
largescale exposure to bat CoVs in the community (multiple million people)
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps

• Species of origin of the virus

• Geographic origin (endemic vs imported via trade, etc.)
• Prevalence of the virus in various species of animals (host
and possible intermediate host)
• Mode of transmission to humans
• Risk reduction strategies for animal to human
transmission
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts

• Investigations into genetic relatedness to other animals CoV’s

• Investigations into host susceptibility (in-vitro, receptor binding

studies, etc.)
Overview of state of the art and outline of key
knowledge gaps
• State of the art
• Knowledge gaps
• Ongoing research efforts
List of questions to be addressed
1. What is the transmissibility in different epicentres over time, including the R0/Rt, serial interval,
modes of transmission, environmental factors etc.?
2. What is the severity of disease, different levels of fatality risk stratified by baseline risk groups?
3. Who is susceptible, are children infected/infective, do all infections result in neutralizing
immunity?
4. What is the impact of interventions, such as non-pharmaceutical interventions, mobility
restrictions, social distancing, etc?
Overview of state of the art and outline of key
knowledge gaps – State of the art

Li et al NEJM 2020
Overview of state of the art and outline of key
knowledge gaps – State of the art

Backer et al Euro Surveill 2020

Overview of state of the art and outline of key
knowledge gaps – State of the art

Wu et al Lancet 2020
Overview of state of the art and outline of key
knowledge gaps – State of the art
The model shows that as of
January 23, most Chinese cities
had already received a
considerable number of infected
cases, and the travel quarantine
delays the overall epidemic
progression by only 3 to 5 days.
The travel quarantine has a more
marked effect at the international
scale, where we estimate the
number of case importations to be
reduced by 80% until the end of
February. Modeling results also
indicate that sustained 90% travel
restrictions to and from Mainland
China only modestly affect the
epidemic trajectory unless
combined with a 50% or higher
reduction of transmission in the
community.
Vespignani et al 2020. Preprint available on MedRxiv
Overview of state of the art and outline of key
knowledge gaps – State of the art

… the travel ban slowed the

dispersal of nCoV from Wuhan
to other cities in China by 2.91
days (95% CI: 2.54-3.29)

Tian et al 2020 preprint available at

http://dx.doi.org/10.1101/2020.01.30
.20019844
 Overview of state of the art and outline of key
knowledge gaps – State of the art
Quilty et al Euro Surveill 2020 Cowling et al. BMC ID 2010

Entry screening was associated with an average of 7-12d delay in local

transmission during 2009 A(H1N1) pandemic

…46% (95% CI: 36 to 58) of infected travellers would not be

detected...Airport screening is unlikely to detect a sufficient
proportion of 2019-nCoV infected travellers to avoid entry of
infected travellers.
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps

“Notably,
patient 1 or
patient 3 who
had visited
Wuhan
hospital
might have
been
infectious
before
symptom
onset because
patient 5 was
shedding
virus without
symptoms.”

Chan et al Truly Asymptomatic Transmission ? Rothe et al

Lancet 2020 NEJM 2020
 Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
Presumed Hospital-Related Transmission and Infection
Of the 138 patients, 57 (41.3%) were presumed to have been
infected in hospital, including 17 patients (12.3%) who were
already hospitalized for other reasons and 40 health care workers
(29%). Of the hospitalized patients, 7 patients were from the
surgical department, 5 were from internal medicine, and 5 were
from the oncology department. Of the infected health care
workers, 31 (77.5%) worked on general wards, 7 (17.5%) in the
emergency department, and 2 (5%) in the ICU. One patient in the
current study presented with abdominal symptoms and was
admitted to the surgical department. More than 10 health care
workers in this department were presumed to have been infected
by this patient. Patient-to-patient transmission also was presumed
to have occurred, and at least 4 hospitalized patients in the same
ward were infected, and all presented with atypical abdominal Diamond Princess was carrying 2,666 passengers and 1,045
symptoms. One of the 4 patients had fever and was diagnosed as crew from a range of nationalities when it arrived at Yokohama
having nCoV infection during hospitalization. Then, the patient was on Feb 3. About half the passengers are from Japan. Local
isolated. Subsequently, the other 3 patients in the same ward had health authorities undertook screenings and ordered the
fever, presented with abdominal symptoms, and were diagnosed quarantine after a man on the prior sailing was later diagnosed
as having nCoV infection. with 2019-nCoV in HK. As of Feb 10, 2020, 135 cases have been
Wang et al JAMA 2020 confirmed amongst those on board.
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
Figuring out the clinical iceberg

pH1N1 2009: problem with numerator and denominator

Numerator of “confirmed” deaths likely to underestimate impact on the elderly
Denominator of confirmed cases led to overestimation of CFR by several orders
of magnitude
Wong et al Epidemiology 2013
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
A(H7N9)

SARS-CoV

Leung et al Ann Intern Med 2004

Ghani et al Am J Epidemiol 2005 Yu et al Lancet 2013
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
Should schools be/remain closed, and for how long? Susceptibility, severity and infectivity in children
2008…too little, too late 2009…12-25% reduction in 2018 Flu B
transmissibility…peak delayed

Cowling et al. 2008 EID

Wu et al. 2010 EID Ali et al. 2018 EID
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
Pathogen 𝑹𝟎 Serial interval/ Source Methods
Generation
time
2019-nCoV 2.2 (1.4-3.9) 7.5 (5.3-19) Li et al [1] Serial interval was estimated from dates of symptoms onset of 6 infector-infectee pairs assuming SARS
priors [2]; 𝑅0 was estimated from the epidemic growth rate.
2.68 (2.47-2.86) 8.4 (assumed) Wu et al [3] Serial interval was assumed to be the same as SARS; 𝑅0 was estimated by fitting a transmission model to
the estimated epidemic size of Wuhan based on the number of cases exported to cities outside mainland
China, with assumptions of zoonotic force of infection.
2.6 (1.5-3.5) 8.4 (assumed) Imai et al [4] Serial interval was assumed to be the same as SARS; 𝑅0 was estimated by fitting a transmission model to
the estimated epidemic size of Wuhan based on the number of cases exported to cities outside mainland
China, with assumptions of zoonotic force of infection.
3.11 (2.39-4.11) 5.61 (4.35-7.23) Read et al [5] 𝑅0 and serial interval were jointly estimated by fitting a deterministic SEIR model to the daily number of
confirmed cases in Wuhan and in major cities outside Wuhan in mainland China, and cases exported
outside mainland China, assuming incubation period of 4 days.
1.6-2.9 (𝑅𝑡 ) 7.7 (assumed) Kucharski et al [6] 𝑅𝑡 was estimated by fitting a stochastic transmission model to 1) daily incidence of cases exported outside
mainland China, 2) daily incidence in early phase in Wuhan with no market exposure, and 3) daily incidence
of initial cases in mainland China, assuming incubation period of 4.8 days and infectious period of 2.9 days.

2.0-3.3 (𝑅𝑡 ) -- Majumder et al 𝑅𝑡 was estimated by fitting the cumulative epidemic curve to Incidence Decay and Exponential Adjustment
[7] (IDEA) model.
SARS 2.2-3.6 8.4 (SD 3.8) Lipsitch et al [2] 𝑅𝑡 was estimated from the rate of exponential growth in the number of cases in several other settings and
with the use of data from
Singapore on the mean serial interval.
2.7 (2.2-3.7) -- Riley et al [8] 𝑅0 was estimated by fitting a stochastic transmission model accounting for the effects of superspreading
events.
1.63 -- Lloyd-Smith et al 𝑅0 was estimated from an integrated statistical analysis of the influence of individual variation in
(Singapore) [9] infectiousness on disease emergence.
1.88 (Beijing)
MERS 0.47 (0.29-0.80) -- Kucharski et al 𝑅0 was estimated from branching processes with the offspring distribution following a negative binomial
[10] distribution.
0.45 (0.33-0.58) 6.8 (6.0-7.8) Cauchemez et al R is decomposed into mutually exclusive categories arising from within-cluster transmission, from within-
[11] region transmission and from between-region transmission.
0.91 (0.36-1.44) -- Chowell et al [12] 𝑅𝑡 was estimated from transmission trees reconstructed from successive cases with epidemiologic links.
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
Transmissibility
Analysis of clusters; household transmission studies; estimating transmission parameters from
epidemiological data from different locations; viral shedding studies from exposure to recovery/death

Disease Severity
Case-control and cohort studies; population-wide surveillance; reports from clinical cohorts

Susceptibility
Household transmission studies; convalescent and population-based serological studies

Control and Mitigation Measures

Modeling analysis; comparisons of different locations and mitigation measures
Overview of state of the art and outline of key
knowledge gaps – Conclusions
• Better estimates of key epidemiological parameters to infer transmissibility

• Robust estimates of disease severity is the most urgent question

• Comparative studies across multiple epicentres are needed to understand all

aspects of transmissibility

• Serosurveys in stratified unselected samples in multiple epicentres are

urgently required

• Determine if children are infected, and if so, if they are infectious

Overall goals of a global research roadmap:
epidemiological studies
Objective 1: Understand transmissibility

Objective 2: Understand disease severity and susceptibility

Objective 3: Evaluate control and mitigation measures

Research priorities: Transmissibility

1. Provide robust estimates of the serial interval and generation time

2. Estimate effective reproductive number (Rt) in other cities (i,e. ex-Wuhan) in China
and elsewhere

3. Clarify the relative importance of pre-symptomatic / asymptomatic transmission

4. Determine the role of different age groups in transmission, particularly children

5. Determine the relative importance of possible modes of transmission

6. Determine environmental effects on virus survival and transmission

Research priorities: Disease Severity &
Susceptibility
1. Provide robust estimates of the risk of fatality of hospitalized cases, by age or
other important groupings

2. Provide robust estimates of the risk of fatality of symptomatic cases, by age or

other important groupings

3. Identify groups at high risk of severe infection

4. Determine if children are infected, and if so, if they are infectious

5. Determine if all infections result in neutralising immunity

Research priorities: Evaluate Control and Mitigation

1. Provide impact estimates of travel restrictions, border screening and quarantine

policies on non-local spread

2. Estimate the effects of social distancing measures and other non-pharmaceutical

interventions on transmissibility

3. Predict the most effective measures to reduce the peak burden on healthcare
providers and other societal functions
Clinical characterization and management
• State of the art
• Knowledge gaps
• Ongoing research efforts
List of questions to be addressed
1. What is natural history of disease, prognostic factors for severe disease, including
pregnant women and young children?
2. The relationships between viral load, location, antibody responses, and clinical disease
and transmissibility? optimal sampling protocols for diagnosis?
3. What are the core endpoints for clinical trials.
4. What is optimized standard of care for the disease? adjuvant therapies for patients and
contacts? supportive care interventions for critically ill patients?
5. How to operationalize implementation by capitalizing on clinical trial networks?
Clinical Characterization and
Management: Dedication to Patients
 Clinical Characterization and
Management: Illness Spectrum

Asymptomatic Mild Moderate Severe

? ?
 Overview of state of the art and outline of key
knowledge gaps – State of the art
JAMA. doi:10.1001/jama.2020.1585

• 138 consecutive hospitalized White cells 4.5 (3.3-6.2)

Symptoms
patients Lymphocytes 0.8 (0.6-1.1)
Fever 98.6%
• Zhongnan Hospital, Jan 1 to Jan
28 Fatigue 69.6% Neutrophils 3.0 (2.0-4.9)

• Age 56 years (IQR, 42-68; range, 22- Dry Cough 59.4% Platelets 163 (123-191)
92) Creatine kinase 92 (56-130)
Anorexia 39.9%
• Sex: 54.3% Men Myalgia 34.8% Lactate dehydrog 261 (182-403)
• Comorbidities: 46.4% Bilirubin 9.8 (8.4-14.1)
Dyspnea 31.2%
• Hypertension (31.2%) Creatinine 72 (60-87)
• Cardiovascular (14.5%) Sputum 26.8%
Procalcitonin 49 (35.5%)
• Diabetes (10.1%) Sore throat 17.4%
Overview of state of the art and outline of key
knowledge gaps – State of the art
JAMA. doi:10.1001/jama.2020.1585
Onset of symptoms to:
Dyspnea 5.0 (1.0-10.0) days
Hospital Admit 7.0 (4.0 - 8.0) days
ARDS 8.0 (6.012.0) days
Incubation mean 5-6 (range 2-14) days*

Critically Ill Patients were

Older (66 years vs 51 years)
More likely to have comorbidities (72.2% vs 37.3%)
Overview of state of the art and outline of key
knowledge gaps – State of the art
Of 138 HOSPITALIZED Patients*
85 patients (61.6%) still hospitalized
47 patients (34.1%) discharged
6 patients (4.3%) died
Median stay 10 (7.0-14.0) days Mortality of hospitalized
patients is still uncertain
Of 36 ICU patients* but may be >5-15%*, **
11 (31%) still in the ICU
9 (25%) discharged home
10 (28%) transferred to general wards
6 (17%) died
JAMA. doi:10.1001/jama.2020.1585 *As of February 3, 2020
**LANCET. doi.org/10.1016/S0140-6736(20)30183-5
Overview of state of the art and outline of key
knowledge gaps – State of the art (*IPC)
• Nosocomial transmission 41% patients (N=57)

❖ Patients other admit diagnoses (12.3%, N= 17)

❖ Health professionals (29%, N=40) *

• 31 (77.5%) on general wards
• 7 (17.5%) in the emergency department
• 2 (5%) in the ICU

* 10 Health professionals presumed infected by one patient

JAMA. doi:10.1001/jama.2020.1585
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
• Natural history and clinical course particularly in special populations:
• severely ill, pregnant, children, elderly

• Optimal selection of anti-viral agents and interventions targeting the virus

convalescent plasma, poly- and monoclonal antibodies, IVIg (*therapeutics)
• Compassionate use in the absence of controlled trials is now ongoing.

• Optimal selection of strategies for adjunctive therapies

• immunomodulatory agents (IL-1ra, interferon), steroids, ACE inhibitors,
vitamin C, statins, anti-arrhythmics
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
• Optimal selection of supportive care (ICU) interventions,
• oxygen or fluid management strategies
• ventilation strategies

• Reducing nosocomial spread. (*IPC/lab/social science)

• mode of nosocomial spread: direct patient care or other non-patient
areas, ventilation

• Viral kinetics to inform clinical care and discharge criteria (*Lab/IPC)

• shedding of virus, transmissibility
• optimal sampling techniques
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
85 registered studies in China
• 34 recruiting interventional studies (including lopinavir/ritonavir, remdisivir) washed
microbiota transplantation, arbidol, glucocorticoids, steroids, ruxolitinib combined
with mesenchymal stem cell infusion, TCM, hydroxychloroquine, nasal high-flow
preoxygenation assisted fibre-optic bronchoscope intubation.

• 51 non-recruiting studies interventional studies (favipiravir, baloxivir, arbidol,

interferon, darunavir/cobicistat), interferon, intravenous Immunoglobulin,
hydroxychloroquine steroids, umbilical cord blood mononuclear cells and traditional
Chinese medicines.

• Mental health and psychological interventions on doctors, nurses and patients*

Overview of state of the art and outline of key
knowledge gaps – Conclusions
• Recent observational studies are providing some initial clinical
characterization, but questions remain.
• Special populations such as young children and pregnant women,
• Outcomes in hospitalized patients,
• Viral kinetics, transmission
• Effective antiviral, adjunctive and supportive care therapies.

• Ongoing clinical studies and trials are addressing some of these issues,
but mapping of studies/trials needs to be rapidly done
• Core CRF and core outcomes are essential.
• Implementation of clinical trials using clinical networks
2019 novel Coronavirus
Global research and innovation
forum: towards a research roadmap

Infection prevention and

Control, including protection
of health care workers
John Conly, Canada
Anna Levin, Brazil
Infection Prevention and Control including
Protection of Health Care Workers
Overview

• State of the art

• Knowledge gaps
• Ongoing research efforts
Nature NEWS
07 February 2020

Did pangolins spread ……….. coronavirus to people?

State of the art – 2019n-Cov detection
Patient specimens
• BAL samples (Zhu NEJM 2020) + viral isolation
• Nasopharyngeal/oropharyngeal (NP/OP) swabs
➢ multiple reports of detection in NP/OP swabs; sensitivity and specificity not known
➢ shedding over time - Chan (Lancet 2020) found + RT-PCR in NP/OP swabs of a child
with CT changes c/w infection but reportedly ‘asymptomatic’
➢ exact duration of shedding not known with certainty
• Serum
➢ Chan (Lancet 2020) also showed + RT-PCR of serum in one patient
• Stool
➢ Investigators in Shenzhen and Washington State have detected 2019-nCoV
RNA in the stool of infected patients (ProMed, Holshue NEJM 2020)
➢ No reports have demonstrated live virus recovery in stool for 2019-nCoV
 State of the art – 2019-nCov
Environmental specimens
➢ Potential intermediate host (pangolin) based on 99% WGS similarity (Nature News Feb 7 2020)
Healthcare workers (HCWs)
• Looking at three separate time intervals (before Jan 1, Jan 1-11, Jan 12-22), 0%, 3%, and 7%
HCW infections reported in a series of 425 Chinese patients from Wuhan (Li, NEJM)
• One HCW reported as a confirmed case outside of China
• In a single-center case series of 138 hospitalized 2019-nCoV confirmed cases in Wuhan, China,
presumed hospital-related transmission was suspected in 41% of patients (Wang, JAMA)
Public health interventions - mathematical modeling
➢ Reproductive number range R0 = 1.96 to 6.47 (Du et al, Medrxiv; Tang et al, Clin Med)
➢ Effectiveness of intervention measures; enhancing quarantine/isolation (including travel
restriction) following contact tracing and reducing contact rate can significantly lower the peak
and reduce the cumulative predicted number of infected individuals (Tang, Clin Med)
State of the art – 2019-nCov – ongoing research
84 ongoing research studies on 2019n-Cov (WHO-International Clinical Trials Registry
Platform): NONE are on IPC but may be non-registered
Source: http://apps.who.int/trialsearch/AdvSearch.aspx?SearchTermStat=117&ReturnUrl=%7e%2fListBy.aspx%3fTypeListing%3d0

Current research
• SR on use of masks in the community
• Feasibility of environmental sampling /screening of people under quarantine
• Epi study of 20 and 30 generation transmission
• Environmental sampling of surfaces surrounding the affected patients
• PCR tests on respiratory secretions of affected patients by day of illness
 State of the art - evidence from SARS-CoV and
MERS-CoV relevant to IPC
➢ Droplet and contact – multiple studies demonstrated compliance with gloves, gowns and medical
masks or N95s were adequate to prevent transmission for SARS; major risks exposure of eye and
mucous membranes to resp secretions and AGMPs, ie intubation (opportunistic airborne);
no association with contact with urine/stool

➢ HCW spread - associated with inconsistent or improper PPE use for SARS/MERS-CoV outbreaks;
Infections in HCWs: 22% and 25% for SARS and MERS, respectively

➢ Risk factors for nosocomial spread of MERS-CoV in two large outbreaks in Saudi Arabia and South
Korea found ER/Ward overcrowding and sub-optimal control of visitors were factors

➢ Transmission of MERS-CoV was not documented in an investigation of mostly asymptomatic and

pauci-symptomatic cases and their household contacts

➢ Asymptomatic cases uncommon – one study of MERS cases found 80% of “asymptomatic” persons
actually had symptoms on close questioning
Seto WH et al Lancet 2003;Raboud J et al Plos One 2010; Jefferson et al Cochrane Rev 2011; Oboho IK et a NEJM 2015;Kim SW CID 2017; Cheng VC et al
Antiviral Res 2013; Van Kerkhove MD et al Sci Rep. 2019.
IPC research gaps and respective priorities (1)
1. Modes of transmission
• Body fluids, target tissues for entry, airborne spread, vertical transmission
2. Duration of transmission
• Duration of shedding, asymptomatic shedding, duration IPC precautions
3. Environmental stability
• Viral survival on surfaces and other media, factors influencing stability
4. PPE and IPC measures
• Relative importance of specific PPE/IPC measures, type of mask and eye
protection, airborne vs droplet precautions, PPEs for triage, spatial
separation distances, risks factors for HCWs’ exposure
IPC research gaps and respective priorities (2)
5. Cleaning, disinfection, and waste management
• Efficaceous disinfectants, treatment of sewage, UVGI, surface coating
6. Isolation and quarantine
• Cohorting vs single rooms, costs and resource implications for cohorting, criteria for,
principles and cost-effectiveness of quarantine, and unintended consequences of
quarantine and isolation
7. Behavioural change and social science
• Best approaches to communicate policy recommendations, role of media coverage,
precautions for home care, most frequent IPC lapses, barriers and facilitators influencing
HCWs compliance, human factors & ergonomics, isolation and PPE fatigue
8. Community IPC
• Use of mask by healthy people, precautions for home care, community/family
members education, dead bodies
9. Innovation
• Point of care (PoC) testing, PoC sensors and wearable monitoring, technologies to avoid
unnecessary exposure and transmission, engineering, chemistry and molecular science
of surfaces, design to minimise touchpoints in acute health care facilities
Ensuring coordination across research areas
• Virus - natural history, transmission and diagnostics
• Animal and environmental research (to inform outbreak
control measures)
• Epidemiological studies
• Clinical characterization and management (IPC in specific
procedures)
• Therapeutics R&D (prophylaxis)
• Candidate vaccine R&D (prevention in community and HCWs)
• Ethical considerations for research
• Integrating social sciences in the outbreak response (behavioural
change)
 Conclusions
➢ Many core principles already exist for IPC based on
previous documents
➢ Need to ensure co-ordination across other themes
to allow science to direct IPC recommendations if
2019-nCov differs substantially from other known
zoonotic CoVs
➢ IPC recommendations should be evidence-based
➢ Need to engage investigators globally to expediently
conduct high quality studies to enhance the ipc
evidence base
2019 novel Coronavirus
Global research and innovation
forum: towards a research roadmap
Thematic area: Therapeutics
Dr Marco Cavaleri
 Overview of state of the art and outline of key
knowledge gaps – State of the art
• A landscape of therapeutics was drawn to summarize the existing evidence
to support their use against 2019-nCoV
• Prioritization exercise:
• Remdesivir
• Lopinavir/Ritonavir + (interferon-𝛽)
• Master Protocol being developed for a multi-center adaptive RCT to evaluate
the efficacy and safety of investigational compounds
• In vitro and modelling studies
• Ongoing clinical trials in China: e.g. Randomized, Double-blind, placebo-
controlled studies to evaluate the efficacy and safety of Remdesivir
(mild/moderate and severe cases)
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
• Insufficient knowledge of clinical evolution of 2019-nCoV disease
• Insufficient epidemiological information to precisely guide the definition of
the target population and end-points for efficacy trials
• In vitro/in vivo activity against 2019-nCoV
• The appropriate dosage of therapeutics to use against 2019-nCoV
• Data on efficacy and safety of available candidate therapeutics against 2019-
nCoV
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
• In vitro studies of antiviral agents
• Cross-reactivity studies to evaluate mAbs developed against SARS
• Clinical trials in China (>85):
• Remdesivir
• Lopinavir+Ritonavir
• Tenofovir, Oseltamivir, Baloxivir marboxil, Umifenovir
• Novaferon
• IFNs
• Chloroquine
• Traditional Chinese Medicines: Lianhua Qingwen
Overview of state of the art and outline of key
knowledge gaps – Conclusions
• No therapeutics have yet been licensed against 2019-nCoV
• In order to reduce mortality and improve clinical disease outcome
there is an urgent need to prioritize investigational candidates most
suitable for efficacy trials
• Clinical trials conducted under a Master Protocol will aim to
evaluate the efficacy and safety of these therapeutics across
multiple locations
List of questions to be addressed
1. In addition to the current prioritized therapeutics (remdesivir, liponavir/ritonavir), what other Rx
could be considered (e.g. other repurposed drugs, mAbs, polyclonal Abs, convalescent plasma,
new compounds)
2. Role of IFNs - Role of host-targeted therapies
3. Pre-clinical studies: in vitro/animal models
4. Efficacy trials protocols (end-points and selected trial population)
5. Post-exposure prophylaxis and/or prophylaxis studies
Overall goals of a global research roadmap?

Objective 1: Identification of candidates for clinical evaluation in

addition to the ones already prioritized

Objective 2: Multicenter master protocol to evaluate efficacy and

safety

Objective 3: Coordinated collaboration for therapeutics evaluation

2019 novel Coronavirus
Global research and innovation
forum: towards a research roadmap
Candidate Vaccines R&D Subgroup
Overview of state of the art and outline of key
knowledge gaps
• State of the art
• Knowledge gaps
• Ongoing research efforts
Objectives
1. Develop a research plan that will facilitate the development and evaluation of nCoV vaccines.
2. Provide a mechanism to promote performance of key research tasks, and to share information
about performance.

Disclaimer: This presentation includes incomplete discussions that are the result of brainstorming sessions.
The group hasn’t yet reached clear conclusions about these issues.
Overview of state of the art and outline of key
knowledge gaps – State of the art
Activity Complete?
List of candidate vaccines developed against nCoV ✓
List of candidate vaccines developed against SARS ✓
List of candidate vaccines developed against MERS ✓
List of coronavirus animal model ✓
Preliminary vaccine prioritization for clinical trials (nCoV) ✓
Summary of evidence on vaccination-related disease enhancement Ongoing
Assessment of cross-reactivity of nCoV with other coronaviruses Ongoing
Vaccine Efficacy Trial Master protocol synopsis ✓
Vaccine Efficacy Trial Master protocol Ongoing
Mapping of viruses and reagents ✓
nCoV structural characterization ✓
Overview of state of the art and outline of key
knowledge gaps – State of the art
# of candidates Pre-Clinical Stage Clinical Stage
vaccines
nCoV 5 5 0
SARS-CoV* 33 31 2
MERS-CoV* 48 45 3

*Studies to assess immunological cross-reactivity with other coronaviruses being planned

MERS SARS
# of animal models 8 7
Animal models
• Mouse is obvious first choice. Additional models should be studied to see
which models best mimic human infection and may be best suited to
studying enhanced disease or identifying potential correlates of protection.
Animal models are also useful in evaluation of antivirals.
• Discussion of animal models needed for 1st-in-human studies. Prioritization
and other needs may be different from regulatory needs. Animal models
may help to address preclinical enhancement issues, but other strategies
may also be employed (e.g., informed consent, initial vaccination of
volunteers at low risk for nCoV exposure)
• CEPI is supporting work on ferret model in Australia.
Immune response assays
• ELISA
• For vaccine response as well as evaluation of background seropositivity
• Standards may be important
• Neutralization
• BSL-3
• BSL-2 (pseudovirions)
• Will need comparison/validation of results relative to nCoV neutralization (note that
pseudovirion neutralization for MERS was more sensitive than PRNT, though with correlation)
• Strategies include lentivirus, VSV, different nCoV components
• Large stocks for distribution will be useful
• Analysis of CD4+, CD8+, and cytokine responses to determine which if any
are related to protection or enhancement of disease.
Evaluating potential for enhanced disease
• Potential importance of cellular tropism (monocytes/macrophages)
• Potential importance of CD8-mediated immune responses
• Potential importance of high neutralizing responses
• Animal models to study enhanced disease
• Role of human clinical trials to evaluate enhanced disease
Clinical trial/Study design
• Study design
• Phase I, II
• Goals: safety, comparison and prioritization of vaccine candidates
• Phase III
• Goals: Demonstrate safety, efficacy and evaluate potential for enhancement of disease
• Phase IV
• Goals: Additional real-world safety and effectiveness
• Should vaccine be tested in those with greatest risk from disease (e.g.,
elderly, immunocompromised) vs. those in whom clinical trials could most
expeditiously evaluate efficacy? Immunogenicity in these special target
groups will nonetheless be important to evaluate.
• Importance of clinical endpoint efficacy studies
Cell culture
• Required to optimize neutralizing assays, grow up virus stocks for
other experiments including evaluation of cross-reactivity. Virus
reported to grow well in Vero cells.
• Important to know that virus will stay genetically stable through cell
culture passage. Sequencing results pending from several labs.
• Large stocks will be useful, including standardized stocks for
challenge experiments.
• Also important for antivirals
Cross-reactivity
• Antigens
• Monoclonals vs. SARS, MERS
• Antibodies vs. nCoV
• Other

Working Group on Vaccine Prioritization

“Participants recommended that, given current knowledge and vaccine development
status, vaccine approaches targeting the novel coronavirus should be prioritized for
further development over vaccine approaches targeting other coronaviruses in the
context of the nCoV global outbreak, noting that the development of vaccines for other
coronaviruses remains a public health priority. ”
For individual vaccine candidates
• Potency assays for individual vaccines
• Process development (may be more complex for live-attenuated or
vectored vaccines)
• Formulation (excipients, adjuvants and preservatives)
• Filtration (for sterility)
• Storage temperature (stability)
• Route of administration
• Presentation (monodose vs. multidose; lyo vs liquid)
• Process validation
• Consistency

Note this is a partial list, and is not intended to be comprehensive at this stage
Relating TPP to vaccine candidate prioritization
A. 1 dose Vaccine type Potential
Advantages#
B. Potential for high level neutralizing Ab
• Inactivated/adjuvanted B,C,F
C. previously proven strategy
• Subunit/adjuvanted B,C*
D. likely to induce cytotoxic CMI response
• Live-attenuated A,B,C,D,E
E. Lower theoretical risk of enhancement?
• Vectored A*,B,C*,D,E,G
F. Speed of development,
• DNA B,D,E,F,G
G. Capability to rapidly make large quantities
of vaccine • RNA B,D,E,F
H. Duration of immunity
I. Vaccine stability (i.e. not prone to *May be an advantage for some examples of this
mutation) vaccine type
J. Cost/dose #This is notional and not meant to portray conclusions
about advantages or disadvantages of any specific
vaccine
Overlap areas
• Natural history of disease
• Pathogenesis in humans, cause of death, etc.
• Kinetics and durability of virus-specific humoral and cellular immune responses in mild-
moderate and severe (survivors and non-survivors) of nCoV illness
• Extent of subclinical infection
• Shedding sites (early results suggest significant shedding)
• Clinical data to support case definition for clinical trial endpoints (fever+viremia vs. severe
disease, perhaps other endpoints should be considered if viremia is transient?)
• Epidemiology
• Attack rates/fatality rates/modeling?
• Will support clinical trial design
• Diagnostics
• Assays to support case definition for clinical trials and epidemiological studies
• PCR assays
• Other case-definition related assays
Web-based Data Sharing Tool
• Who has reagents? (Currently, more detail is available in summary of most
recent Cross-reactivity workgroup call)
• Virus (in China, Australia, UK, Canada, France, Germany, US, others)
• Purified spike protein (VRC) and spike protein subunits and domains (WRAIR) (in
limited supply)
• Plasmid used to express spike protein (VRC) and spike protein subunits and
domains (WRAIR)
• Serum and B cells (in very limited quantities, request through US government)
• Monoclonals (production underway)
• Who is working on key questions?
• What are results?
• What are needs?
Key research reagents for vaccine development
• Standardized stocks
• Viruses
• Pseudovirions
• Standards for immunological assays
Other considerations
• Regulatory harmonization (esp. preclinical studies, clinical trial endpoints)
• Will be topic of March 2020 meeting in Brussels, sponsored by ICMRA
• Manufacturing/filling capacity (in facilities that have been or could be
inspected)
• Other manufacturing/testing considerations (e.g., containment)
• Access to clinical trial sites, etc.
• Intellectual property
• Are there other ways to facilitate sharing of reagents?
• Note parallel efforts (e.g., NIAID DMID/BARDA group to assign sub-groups to
address some of these issues analogous to FANG for Ebola; NIBS working on
challenge stocks, dose, route, etc.)
Overview of state of the art and outline of key
knowledge gaps – State of the art (1/3)
Useful and authoritative ethical guidance documents are in place
• Substantial literature has emerged from past outbreaks
• Ethical issues have been well-characterized and researched, particularly in the domain
of research ethics
• Infectious disease emergencies do not overrule need to uphold universal standards
• Accepted ethical principles admit to adaptation to circumstances

Ebola outbreak response shows that complex research undertakings can be

successful (Saxena et al., 2019; London et al., 2018; Aarons et al., 2018; Schopper
et al. 2017)
• Ethics review was not responsible for bottlenecks and delays in implementation in
studies
Overview of state of the art and outline of key
knowledge gaps – State of the art (2/3)
Ethical principles for multinational research exist (Emanuel et al., 2004)
• Collaborative Partnerships • Favourable Risk-Benefit Ratio
• Social Value • Independent Ethical Review
• Scientific Validity • Informed Consent
• Fair Selection of Study Population • Respect for Recruited Participants
and Study Communities

Key ethical issues can be anticipated (Nuffield Council on Bioethics, 2020; Smith
& Upshur, 2019)
• Community engagement
• Data sharing/data transparency
• Setting priorities of scarce resources
• Health care worker responsibilities and supports
Overview of state of the art and outline of key
knowledge gaps – State of the art (3/3)
Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
• Ethics integration and knowledge translation strategy

• Harmonization of multiple reviews

• Biological Samples, biobanks, and consent

• Inclusion of pregnant women and children in clinical trials

• Companion social science studies

Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
• Ethics of public health countermeasures

• Adaptive trial designs

• Global governance
Research Priority Questions

1. How are ethical considerations best integrated across the

spectrum of research initiatives?

2. What is the status of research ethics capacity globally for rapid

implementation of therapeutic and vaccine trials?

3. What substantive and procedural values should guide

governance of the research initiative?
Overview of state of the art and outline of key
knowledge gaps – Conclusions
• Robust and sufficient ethics knowledge and guidance documents are already
in place

• Ethics and ethics oversight are not barriers to research and innovation

• Key ethical issues in research can be anticipated: community engagement,

data sharing and transparency, priority setting, health care worker supports

• Ethics contributions are, and should be, cross-cutting

Toward a functional governance framework

• Ethical considerations are crucial to governance (Eccleston-Turner et al., 2019)

• Adapt an ethical framework with substantive and procedural components

• Focus on transparency, accountability, adaptability, and inclusion

• Bear in mind the overarching importance of fostering and maintaining trust

Overview of state of the art and outline of key
knowledge gaps
• State of the art
• Knowledge gaps
• Ongoing research efforts

1. What are effective strategies to promote acceptance and adherence to public health measures aimed at
limiting 2019-nCoV human-to-human transmission?
2. How can we rapidly identify secondary impacts of the outbreak and outbreak control measures, and deliver
effective strategies to mitigate potential harms?
3. What are effective strategies to ensure continuity and prevent overwhelm of clinical services (including sexual
and reproductive health services)?
4. What is the best way to protect the physical and mental health of healthcare workers?
5. How can we rapidly involve communities in the design, delivery and dissemination of of clinical research?
6. What are the best strategies to disrupt the flows of misinformation on social media platforms?
Overview of state of the art and outline of key
knowledge gaps – State of the art
Impact of public health measures
Impacts of quarantine (Rubin et al 2020), to restrict travel, close schools, close businesses;
Secondary impacts: Lack of sufficient protective equipment (Mahase 2020), other healthcare needs (Woods 2020)

Social drivers of transmission

Growth in high speed train travel and air travel, Lunar New Year (Zhao et al 2020)

Impact on healthcare workers

Frontline staff, especially nurses, at risk; protective psychological factors – good IPC training, confidence in IPC, self
efficacy in role, notions of solidarity, altruism, organizational support; Burnout/ PTSD risk factors: social isolation,
risk of stigma, higher perception of risk of illness, inadequate training (Brooks et al 2018)

High circulation of myths and misinformation

Panic and mental health impact (Bao et al 2020); Social networks can be instrumental for spreading offline
behaviours (Jones et al 2017)

Anticipate need for involvement and engagement in clinical research

 Overview of state of the art and outline of key
knowledge gaps – Knowledge gaps
Public Health
What are effective strategies to promote acceptance and adherence to public health measures aimed at limiting 2019-nCoV
human-to-human transmission?; How can we rapidly identify secondary impacts of the outbreak and outbreak control
measures, and deliver effective strategies to mitigate potential harms?

Clinical
What are effective strategies to prevent overwhelm of clinical services (incl. SRH services)?;How to protect the physical and
mental health of healthcare workers?; How to involve communities in plans for clinical research?

Community engagement;
What are effective ways to engage large, urban populations?; What is the most effective way to systematically assess and
address stigma and xenophobia related to 2019-nCoV?

Media and communication

How are people using social media?; What are best strategies to disrupt the flows of misinformation on social media
platforms?; What are the best strategies to address stigma and xenophobia and promote acceptance and inclusion?

Sexual and reproductive health

How can we best communicate the risk of mother to child transmission for 2019-nCoV?
Overview of state of the art and outline of key
knowledge gaps – Ongoing research efforts
Evaluating impact of public health measures:
Effectiveness of lockdown (lead:Xian Jiaotong University), Economic impact of extended business closures (lead: Zhejiang
University), psychological and behavioural responses pre-post exposure to live animals (lead: Fudan University),
implementation and performance of epidemic prevention strategies (lead: Shanghai Municipal People's Government
Development Research Center) individual prevention behaviours (Pengpai), evaluating eGovernement as an info source
(lead: Center for Public Policy Research at the East China Normal University and Research Institute)

Investigating role of early warning and emergency risk communication (China)

Evidence on protection of healthcare workers

Help seeking behaviours to manage patient demand

Stakeholder readiness to participate in medical research

Media surveillance
Public reaction (lead:Fudan Uni) For improved risk communications (lead: SoNAR-Global)
Overview of state of the art and outline of key
knowledge gaps – Conclusions
Broad agenda flexible
Priorities shaped by needs and context at local, national and regional levels; must stay open to new agenda items

Operational endpoints
To be useful, research needs rigourous, rapid methods and quick turn around to inform operations; medium term
academic track also important.

Social science contribution is cross cutting

Many priorities are cross cutting, needs for engagement with many different stakeholders to understand priorities
and end user needs.
Overall goals of a global roadmap: social
science research for operational response
Objective 1: To establish a framework for identifying priority areas where
social science research can contribute to achieving the goals of the strategic
response plan.

Objective 2: To build and strengthen networks of social science researchers

operating in different global regions.

Objective 3: To support operational partners, with focus on local partners

and national public health, with tools and evidence, to account for social and
behavioural dynamics in their actions.
Research priorities: public health

1. What are effective strategies to promote acceptance and adherence to public health
measures aimed at limiting 2019-nCoV human-to-human transmission, e.g.
isolation, social distancing, quarantine, public health prevention advice etc.?

1. What are effective strategies to promote acceptance and adherence to infection,

prevention and control measures in community settings?

1. How can rapid investigation of social drivers of transmission contribute most

effectively to public health response measures?

1. How can we rapidly identify secondary impacts of the outbreak and outbreak
control measures, and deliver effective strategies to mitigate potential harms?
 Research priorities: clinical
1. What are effective strategies to ensure continuity and prevent overwhelm of clinical services
(including sexual and reproductive health services)?

1. How can organisations best support the physical and psychological health of their staff, including
clinical (nurse, doctors, allied health professionals, administration (managers, receptionists etc.) and
support staff (cleaners, porters etc.)?

1. What are effective strategies to promote acceptance and adherence to infection, prevention and
control measures among healthcare worker?

2. How can understanding of protective psychological factors from SARS contribute to strategies for
mitigating burnout of healthcare workers?

1. How can understanding of patient and public help seeking behaviours through traditional and non-
traditional routes inform strategies for self-triage and home care?

1. What are the best strategies for rapid engagement and good participatory practice for medical
research?
Research priorities: media and
communication
1. How are people using social media to access information? What drives
deliberate circulation of conspiracy misinformation, stigmatizing and
xenophobic messaging, and conspiracy regarding 2019-nCoV?

1. What methodologies exist for tracking and disrupting knowledge circulation

(media, social media etc.)? Do we have the right levers to tackle the spread
of misinformation?

1. How can insights around rumor spread help target communication and
messaging for this outbreak?
Research priorities: engagement
1. What are effective methods to engaging priority community groups,
including large urbanised populations, those working in travel and tourism,
migrants, underserved populations?

1. What is the most effective way to systematically assess and address stigma
and xenophobia related to 2019-nCoV?
Research priorities: sexual and reproductive
health
1. What is the risk of mother to child transmission and sexual transmission of
the 2019-CoV and how can we best communicate that risk?

1. What is the most effective way to ensure readiness to respond and expand
on social science needs in SRH according to new evidence generated?