Debating Ideas is a new section run separately from the main African Arguments site. It aims to reflect the values and editorial ethos of the African Arguments book series, publishing engaged, often radical, scholarship, original and activist writing from within the African continent and beyond.
Everyone should have a fighting chance of surviving this coronavirus. Social changes control the power of the response, since the epidemiology of Covid-19 is worse than for Ebola. Medical biotechnology changes can be crucial to individuals’ survival, if they are given enough time before they are infected. The response to Covid-19 in Africa can do this.
The good news is that biological research and development capacity have increased by orders of magnitude since the Ebola epidemic in West Africa. My rough estimate is that technology and capacity are at 1,000 times the level at the end of the epidemic in 2016. The difference from the start of the West Africa outbreak in 2014 is so great that it cannot really be expressed.
An implied consequence is that effective drugs for treatment of severe cases should be in trials this summer. If disease progression can be stopped for severe cases before lung damage, the need for respirators – of any kind – would be greatly reduced.
If any stage of research, development and production is destroyed in one country, due to Covid-19 infection of researchers or loss of biomedical supply chains, then hopefully other countries can continue that work in their own way.
Delaying the growth phase of the epicurve, and lowering its peak, means that more people will have a chance of survival, even when advanced biomedical technology in hospital care is scarce.
For a number of reasons, it is far more likely that a reasonably effective and reasonably safe drug will be developed long before a safe and effective vaccine.
Learning from Ebola in West Africa and Eastern DRC
A lot could be learned from the just-ending Ebola epidemic in the Eastern Democratic Republic of the Congo (DRC). The lessons learned are just in time for the Covid-19 pandemic.
The concepts used in drug and vaccine development for Ebola in West Africa, but not successfully tested, were proven in Eastern DRC. The Merck vaccine, in particular, was a crucial tool. Its survival from brilliant lab research in Canada to a well-produced effective vaccine was very, very contingent. This should not be the case, now, for new drugs and vaccines.
In Eastern DRC, the monoclonal antibody drugs, which I think of as manufactured passive immunity, were improved upon, while the concept of their use, and potential effectiveness, were validated.
Zmapp, experimental in 2014–16, was made part of the standard of care in the drug trials. The trials were stopped when two similar new drugs showed significantly improved survival. One was a different choice of three monoclonal antibodies, similar in concept to ZMapp. The other was mAb114, a single monoclonal antibody developed in a collaboration led by Dr Muyembe-Tanfum from the Institut National de la Recherche Biomédicale (INRB). This mAb was developed from the antibody repertoire of a survivor of the 1995 Ebola outbreak in Kikwit.
That the trials could even take place in Eastern DRC is the result of pushback, confrontation and eventually cooperation, accommodation and collaboration that changed laws, regulations, and trial design for drugs and vaccines. All for the better, but it is a long story.
Early use of drugs, during their development for a disease, has a very different medical regulatory environment now. This is partly due to the scope of the pandemic. In the United States, these involve compassionate use, conditional use, broader definitions of research trials and other changes.
The foundational regulatory changes in the United States came as a result of AIDS activism, early in that pandemic, by groups like ACT-UP. There are some lethal ironies about this. Everyone has benefitted from these changes, including as of now (3 April 2020) blood banks in New York and elsewhere which are producing Covid-19 survivors’ serum for experimental compassionate use and trials; as well as other drugs being tried in severe cases.
Perhaps the greatest changes during Ebola in Eastern DRC involve the contested politics and sociology of the international medical response. This should be written about by others.
Even from a great distance some changes can be noticed. The culture of medical responses, within nations and internationally, has had an asymmetry. Institutionally there is a tradition to speak but not to listen.
Under the brutal conditions in the outbreak regions, faced with people who reacted to the Riposte (response) as itself a kind of peste (plague), there appear to have been many changes made.
One of the most useful social-technical changes from the Eastern DRC outbreak was to have community care for Ebola embedded within more comprehensive health services. This may well apply to parts of the Covid-19 response in Africa, now. The community care centre concept will have to be adapted, changed, or adapted to be part of community protection in some places.
Informed consent: a rough guide
Early in 2014, Lawrence Gostin, at Georgetown University and Director of the WHO Collaborating Center on National & Global Health Law, told us that informed consent was necessary, even during an epidemic – or pandemic in this case. This was not easy, because the technology used is sometimes obscure to anyone not directly working in a specialised sub-field.
I noticed then that there are several simplifying ways to think about the large array of proposed drugs and vaccines, or vaccine-like drugs. These probably still apply in 2020.
1. Has the therapeutic strategy ever successfully been used to target a very similar disease, a similar disease, or any disease at all?
Because the range we saw went from proven to be successful in a closely related disease, to have never been successfully tried for any disease at all.
2. How far in the testing hierarchy has the therapeutic progressed?
At the lowest level, this starts with better or worse tissue culture models. Does the therapeutic leave the target cells alive while blocking or destroying the virus? Tissue culture screening may have most value for flunking candidates. Passing this test says little about eventual success (except where biochemical mechanisms of action add value).
Animal testing then proceeded in an order from mice and other rodents, and possibly other small mammals – where results are known to differ from human response in their detail – up through non-human primates (NHPs) and the particular species of NHPs that are considered the gold standard for a particular kind of disease in humans.
Human testing then starts with an anomaly: the very limited number of volunteers for phase zero or phase one are often middle class, altruistic, often white, well informed people who live near major research facilities in places like Bethesda, Maryland; Cambridge, England; or Switzerland (for Ebola in West Africa). Biases introduced by this self-selection can be accounted for in the larger phase two trials. These also have their own issues.
It is easy to see the problem. The more accessible, quicker and cheaper the system, mice being the prime example, the more likely it is to eliminate a candidate that might have worked for people.
The work-around that has become much more common are the so-called H-mice, for humanised mice. Humanised in the sense that they have had their own immune systems obliterated to a greater or lesser degree and replaced by human cell lines. So, to a greater or lesser extent, depending on the procedures used, they do react to a disease/immune response in a manner much closer to people.
These are very good mice, indeed. We owe them. Under the pressure of a pandemic, their supply also is becoming insufficient, and they may become worth their weight in gold.
Maybe people don’t want to be informed about some things.
One really wants the results of a later, large scale human trial. However, for vaccines in particular, even candidates which have passed all these hurdles and been approved for the largest scale trials – basically interventions – may still fail as ineffective or unsafe; sometimes even after being released for public use.
3. How easy would scale-up be to meet the needs of a crisis, an epidemic or a pandemic?
It is not easy to have safe and effective production of drugs and vaccines. This is where novel untested systems, or drugs that are already manufactured for a somewhat distant or unrelated disease or condition look much more attractive. The novel, untested systems may be very amenable to scale-up – and were chosen for that reason. There may be a plausible, though unproven, biochemical logic to the choice, as well.
Favipiravir was an existing drug, rather distant in its use but plausible, trialed in West Africa for Ebola using a novel trial design that was considered more ethical.
The logic here is that: if it did work, we could make enough of it, fast enough.
4. What are the best targets, and which therapeutics have the best results with the least side effects?
A great number of the drugs, vaccines and vaccine-like drugs have multiple approaches to a single target: prevent viral entry into human cells by attacking the interactions needed for a coronavirus spike (S) protein to bind with a specific (ACE2) receptor on a human cell membrane.
A similar strategy has been used for Ebola and other viruses – block entry in the first place. So, this is a well-tested strategy with successes. Perhaps with too many groups using it, although with great diversity within the same strategy.
So: when therapeutics – or trials – do come perhaps people will find this useful as a starting place.
Learning what not to do
I live in a country (the United States) that is being devastated by failure to act at all, and failure to act in time. We lack testing, PPE for medical workers, ventilators and basic supplies for the general population. We still have inconsistent isolation and physical distancing. The United States and the United Kingdom are both on track to be worse than Italy or Spain. Better models include Taiwan, South Korea, Iceland and others. China is a special case.
We have already seen people left to die without hope, treatment or companionship in Italy and elsewhere. And we are on-track for the same results here as well, starting in New York City. Until the epicurve bends, the number of severe and fatal cases keep doubling.
One of the best descriptions is from Papa Giovanni XXIII Hospital in Bergamo. They describe the devastation in their modern hospital, and then look for what could have been done differently.
‘Western health care systems have been built around the concept of patient-centered care, but an epidemic requires a change of perspective toward a concept of community-centered care… Pandemic solutions are required for the entire population, not only for hospitals. Home care and mobile clinics avoid unnecessary movements and release pressure from hospitals…it is a public health and humanitarian crisis… It requires social scientists, epidemiologists, experts in logistics, psychologists, and social workers. We urgently need humanitarian agencies who recognize the importance of local engagement…. The more medicalized and centralized the society, the more widespread the virus.’
Learning from Africa
Dr John J. Nkengasong, the director of Africa CDC, and Dr Meredith McMorrow, Medical officer in the U.S. CDC had an online press briefing on 2 April. One of the very interesting questions came from South Africa, I quote from the transcript:
‘By many objective measures, the U.S.’s reaction to this pandemic has been delayed, and some critics say disastrous. So why should the U.S. be advising anyone on this, especially African nations that have a decent track record of battling epidemics? And is this a two-way street? Is the African CDC offering any advice or assistance for the crisis in the United States? Finally, could this new dynamic portend a shift in U.S.-Africa diplomatic relations?’
Both presenters were decorous in their responses. Let me generalise the second part of the question: ‘is this a two way street?’
I would say: it should be; absolutely; yes. We need both social epidemic and biotechnological learning and skills and cooperation.
No one knows just how hammered each country and region will be. Nor the long-term consequences of individual infections.
Sars-2 CoV (the virus) has two primary targets, the lungs and the immune system.
Covid-19 (the disease) appears to have five presentations: (1) asymptomatic or with un-noticed symptoms; (2) mild symptoms; (3) symptoms severe enough to warrant hospitalisation; (4) symptoms severe enough to warrant ICU hospitalisation with respiratory therapy to maintain breathing; (5) loss of lymphocytes and leukocytes (cellular components of immunity) combined with out of control inflammation (the ‘cytokine storm’) which can lead to multiple organ failure and death.
When a patient is called ‘asymptomatic’ it refers mainly to absence of respiratory symptoms and fever. Immune system responses may exist and may be important in the long-term (even for asymptomatic individuals) over time.
Many ‘asymptomatic’ individuals will develop symptoms starting within about five days and are pre-symptomatic. Some will not develop recognised symptoms at least for months (the pandemic only began in December) or longer.
Do asymptomatic individuals ‘recover’ (show no virus present), or do they continue to shed virus? What is their immune response status? Are they permanently asymptomatic or on a slow curve, over a year, say, towards more severe symptoms? What happens when they (or anyone) are challenged by a similar virus?
There is long term uncertainty.
Four immunological conditions can lead to the same appearance: never infected; pre-symptomatic with virus shedding; asymptomatic and continuing to shed virus without symptoms; recovered after infection.
The same appearance of non-infection can lead to four different epidemiological consequence.
There is short-term, present-time, social ambiguity as well as uncertainty.
The more people working on this, both biomedically and bio-socially, the better.
Can the social and bio-social epidemic response be improved, based on what is known about the virus and past experience? That’s the hope.,
- Mulangu, S., Dodd, L.E., Davey Jr, R.T., Tshiani Mbaya, O., Proschan, M., Mukadi, D., Lusakibanza Manzo, M., Nzolo, D., Tshomba Oloma, A., Ibanda, A., Ali, R., 2019, ‘A randomized, controlled trial of Ebola virus disease therapeutics’, New England Journal of Medicine 381 (24): 2293–303.
- Nguyen, V.K., 2019, ‘An epidemic of suspicion – Ebola and violence in the DRC’, New England Journal of Medicine 380 (14): 1298–9.
- Niehuus, R. and Stearns, J., 2020, ‘COVID-19: What the US can learn from the DRC’s response to Ebola’.
- Nacoti, M., Ciocca, A., Giupponi, A., Brambillasca, P., Lussana, F., Pisano, M., Goisis, G., Bonacina, D., Fazzi, F., Naspro, R., Longhi, L., 2020, ‘At the epicenter of the Covid-19 pandemic and humanitarian crises in Italy: changing perspectives on preparation and mitigation’, NEJM Catalyst Innovations in Care Delivery 1 (2).
- Transcript available from: Global Public Affairs, Africa Regional Media Hub, U.S. Department of State, Johannesburg, South Africa.
- Richards P., 2016, Ebola: how a people’s science helped end an epidemic, London: Zed Books.
- Richards P., 2020, ‘Preparing for Covid-19 in Africa’.