Diagnostic testing is vital for clinical case confirmation, identification of infected contacts and at a population level for understanding the dynamics of transmission.
Two types of diagnostics are required:
- Kits for viral detection based on virus RNA detection (these are available)
- Tests to provide evidence of past infection which is crucial to understanding the epidemiology of this pandemic. These are not yet available at scale.
In both cases there is a need to develop improved tests that reduce time to conduct tests, promote ease of performance with available technology and reduce costs. Several groups on the continent have the capability to develop such tests.
Currently laboratory-based diagnosis in African settings is mostly carried out by a centralised laboratory that may not yet have the capacity to develop a biobank. There is need to evaluate systems that speed up the logistics of sample collection, transport testing and return of results.
An alternative is to take the service to communities through mobile laboratories capable of delivering immediate results. Collected samples could go back to the central laboratory to constitute biobanks. These biobanks can then be used to: facilitate research for rapid diagnostic tests (RDTs), evaluate newly proposed RDTs and validate the use of technologies like GeneXpert. GeneXpert is advantageous because it has been widely rolled out across Africa and recent data suggests that it can be adapted for COVID-19 diagnosis.
It is important to understand if any variation of SARS-COV-2 will be circulating in Africa during the outbreak. Researchers will need to create a system that can detect genetic mutations and describe the clinical significance of possible genetic mutations. The Intra-African government collaboration in genomic work initiated between South Africa and Nigeria governments could be used to build a network of genomic work focussed on these aspects.
Zoonosis: Africa has many communities that consume wild and exotic bush meat. More studies are therefore needed to identify if there are additional animal sources and routes of transmission. There is need to describe the hosts, or any potential locally available reservoirs for the disease or investigate any evidence of continued local or global spill-over to humans and transmission between animals and humans. All assumptions need to be investigated.
Transmission dynamics: We will also need to understand the socioeconomic and behavioural risk factors for spill-over and transmission between animals and humans. Local or global risks linked to trade and consumption of potentially infected animal species and the communities or occupational groups more at risk across different interfaces need to be described. Local human to human transmission dynamics need to be investigated.
Transmision and Disease modelling:There is an urgent need for representative population data on virus incidence (see 1 above). These data should be used to develop transmission and disease outbreak models that take account of local contextual factors such as population structure, mobility and health system structures. These outbreak models will inform policymaker’s choice of interventions and allow comparison of different approaches under varying circumstances. This will be particularly important in making decisions on how long periods of intensive social distancing or partial or full lockdown of African countries needs to be.
Risk factors for the disease are changing as the disease moves on to community transmission e.g. initial risk factors of travelling to COVID-19 hotspots are being reversed by travel advisories and shutdowns by various countries. The continent can draw from the extensive experience with index HIV testing in sub-Saharan Africa to design protocols for an index contact testing intervention for COVID-19. Local cohort studies, stratification of
patients according to risk profile important to Africa (e.g. HIV, Sickle cell disease) and immune adaptation studies will need to be anticipated and described with specialized comorbid disease management protocols released early.
Asymptomatic subjects: There is need to identify potentially infectious asymptomatic subjects, using implementation research, or cohort studies since these could drive the epidemic beyond the track and trace system. An index case and full contact testing model needs to be implemented while at the same time research the cost benefit potential for such a model to be implemented when the epidemic numbers are high.
Pathophysiology of COVID-19 is not well understood across geographical areas and populations. Currently there is a wide time range given between onset of disease/infection and development of symptoms - stated to appear anytime between 2-14 days. There is need to refine this to allow accuracy in screening and understanding of the case history.
Case definitions: There is a need for standardised and comprehensive data collection to accurately define clinical and laboratory features of confirmed cases. Initially clinical features were thought to be limited to the airway, but recent cases indicate that other systems such as the renal, abdominal and cardiac systems can be affected. Additionally, current cases are reporting appearance of sore throat way ahead of other symptoms including fever.
Most African populations have minimal or no access to ICU care or to ventilators. Research is urgently needed on how to scale care of severely ill patients in these circumstances including assessment of innovative means of positive pressure airway assistance.
Data is needed to protect vulnerable groups from the intense periods of SARS-CoV-2 transmission. Treatment protocols will also need to reflect potential threats to vulnerable groups as they undergo disease management. Work within the vulnerable groups could include those with advanced age, those with concomitant non-communicable chronic diseases including those on immunosuppressive medications and those with infections like HIV & m-TB. Sickle cell patients and patients with rare diseases will also need special attention.
Receptor expression: From basic science ACE2 has now been defined as the receptor-binding domain for SARS-COV-2, it will be important to understand the expression levels, determinants for the expressions in Africa and any related prevalent mutations and their possible clinical relevance. There is an opportunity for groups in Human Hereditary and Health group (H3A) to quickly mobilise and deliver this. This is key if we are to develop genetic or African specific tools to block transmission considering the heterogeneity of the African genome.
Urgency is required to develop locally viable innovations in materials and processes that can address the needs of healthcare workers and care facilities, given the global lack of sufficient personal protective equipment (PPEs). African institutions should participate in the Global Solidarity Prevention Trial for Health Care Workers so that they may be current with knowledge attitude and practices for protecting healthcare workers. The African Academy of Sciences has an opportunity to link innovators and researchers on the continent to the WHO and the Therapeutics Accelerator who have potential trials and products for extended evaluation.
In 2002-2003, during the SARS outbreak, initial drug discovery was done by the help of structural bioinformatics (i.e. modelling drug target protein, identifying potential drug etc). Since 2003, much has changed, but structural bioinformatics still has a huge role in drug discovery for the COVID-19 outbreak and there are groups in Africa which can contribute to this. African groups also can contribute to the screening of large amounts of compounds from electronic databases and identification of potential hits. A limited but capable group of institutions have pipelines to identify potential drug targeting sites rather than active sites and are also able to analyse mutation effect on the behaviour of drug targets.
At a more basic level understanding the host-pathogen interactions is crucial to identify potential inhibitors to block the transmission or limit viral replication.
Many research groups on the continent have extensive experience of delivering clinical trials and these may include the new or repurposed drugs currently under investigation (e.g. Remdezivir, Chloroquine, Hydroxychloroquine in combination with Erythromycin, Tocilizumab).
There is a Global Solidarity Treatment Trial coordinated by the WHO R&D Blueprint team that is set to start soon. African groups should explore possibilities for participation.
Currently there are over 40 COVID-19 vaccines under development and the first volunteers have already received one potential vaccine as part of a Phase I study supported by NIH and CEPI. The African Academy of Sciences is building a Clinical Trial Community (CTC) platform that can provide information on groups capable and ready to evaluate potential vaccines or therapies for the many conditions including global COVID-19 pandemic. The development for this CTC now needs to be accelerated with a sense of urgency as this one-stop comprehensive source of information for operational logistics to conduct clinical trials in Africa will be a critical resource during this phase.
During the webinar, participants highlighted the need to have accelerated ethical review with protocols reviewed and approved on much shorter timelines while retaining the rigorous protection needed from African Ethics Review Committee (ERC’s). There was a proposal to establish a world-class group of ethicists for African countries who would provide ‘independent opinion’ to either provide specific advice to local ethical committees or even to allow some committees to consider accepting a ‘delegated opinion’ particularly for multicentre/multi country studies in this critical period of the disease. ERC’s with little experience, for example, in emergency medicine research or biologics, or research in the comatose patients could access opinion from this group. There is probably a role here for the African Academy of Sciences to institute a credible emergency review committee that is ratified by African countries to assist during this period. Some form of standardization could be instituted with a template used to collect comparative statements with local context from each site to allow for cross-country understanding during protocol review. The Clinical Trial Community (CTC) of the AAS has been working on ethics and regulatory harmonization in coordination with African Vaccine Regulatory Forum (AVAREF) to get the data across the continent. There is potential to build on this work to achieve this.
Multidisciplinary approaches are required in all areas and research protocols should wherever possible have a social science component that provides context specific perspectives e.g. on human / community / household factors where an understanding of behaviours could be key to the design or analysis of the study.
Africa has high density urban areas with very high human interaction for both the middle class and the poor. There is need for proposals to study how to best deliver social distancing, self-quarantine, and isolation in high-density urban areas like slums. Lower economic communities rely on income generated daily to survive and imaginative approaches such as cash transfer through mobile money systems need to be explored as mitigating measures.
Control measures for COVID-19 require the active participation and support of communities, which in turn depends on the availability of clear and transparent information. Work needs to be done to study routes of information flow to give public health officials a chance to curb the misinformation and myths about this virus. Health promotion practitioners need to establish ways to improve public health messaging and social marketing to bring the whole population to take the outbreak seriously without causing panic.
Investigations should be carried out in countries to determine the effects of the advice to residents to work from home. Given the differences in technologies and liberties enjoyed in different countries, it will be imperative for different models to be tried out with outcomes monitored in real time. There are extraordinary efforts needed to continuously build a body of knowledge that helps governments to understand the real impact of digital platforms not just on COVID-19 infection numbers but also on general health, on schooling, on the economy and on future residual effects on social cohesiveness.
The importance of data sharing for all the above areas cannot be overemphasized. Organizations with similar data collection tools have an opportunity to organize a data sharing response that will accommodate varied data, traditionally difficult to correlate, to allow conclusions to be drawn from large volumes of data earlier than is usually the case.
The African Academy of Sciences will support African scientists and innovators to address the challenges facing the world during the COVID-19 outbreak. Numerous groups have expressed interest in participating in related initiatives. The AAS therefore has started maintaining a list of institutions and research teams that have different capabilities in different research areas mentioned in this document.
The impact of this pandemic on individuals, communities and society is unknown. We can only do our best to limit the consequences on all fronts by providing credible research findings to promote the impactful interventions.