Dr Arindam Basu, Strategy Consultant, healthcare and life sciences, explains why we need to be able to see things differently, in order to respond differently in the wake of COVID-19 epidemic
Uncannily, it is exactly a hundred years, since the last serious wave of the Spanish Flu pandemic hit the world in April, 1920. That influenza virus killed millions during the 1918-1920 in the backdrop of World War I ravages. Cut to now, more than half of the world’s population is suddenly placed under widespread and stringent lock-downs for fairly long and uncertain periods, and economies have come to a grinding halt – an unprecedented disruption in response to a rather ‘tricky’ pandemic, COVID-19. Besides, as the socio-economic costs weigh us down, there is a pressing need to re-consider what questions we are asking and what problems we are defining. Are we overestimating the problem, or are we underestimating it? Are we ‘treating’ self-created indices, or are we getting closer to solving the real problem? A streetlight effect must not derail our collective resolve to win this one. We need to be able to see things differently, in order to respond differently.
The genesis of the problem
‘We could be staring at a once-in-a-century pandemic or a once-in-a-century evidence fiasco.’ In my opinion, it is both. The origin of the disease and patient zero details from Wuhan, China, continue to be shrouded in mystery. Is it a natural virus or an engineered one, is another big question. These majorly hinder our understanding of the evolution of the virus and its spread – the projected trajectory of the COVID-19 disease. Further, many discrepancies in the earlier data reported by China and the World Health Organizatio (WHO), are widely acknowledged today. The European ECDC, US-CDC and John Hopkin’s, USA would likely build more credible evidence over the coming weeks, and lead to a more targeted and evidence-backed fight against COVID-19.
SARS-CoV2’s asymptomatic and pre-symptomatic transmission is at the heart of the problem. Some data emerging from cohorts from Iceland, Vo in Italy and the Diamond Princess Cruise Ship are pointing at the asymptomatic carrier subset to be over 40 per cent. In that sense, it resembles more to the influenza viruses than the more recent coronaviruses like the SARS and MERS ones. Further, it is highly infectious too. The basic R0 resembles that of earlier SARS. Besides, increasing evidence points to a significant subset, symptomatic or not, continuing to shed the virus much beyond 14 days, extending to a month or more in some cases. The transmission and further the fatality rates have shown wide variance across countries so far, as seen with Italy and Germany within the EU Block itself. Demographics, weather and cultural conditions seem to play a large role. Virus strain and virulence, and genetic frameworks of communities determining the immune response drive morbidity and mortality patterns. However, given the highly transmissible virus and large number of asymptomatic carriers, even a 0.1 per cent increase over the 0.1 per cent infection fatality rate, known for the seasonal flu or influenza viruses, would mean millions of additional deaths globally. Almost all current models predict the SARS- CoV2 IFR to be well over 0.5 per cent.
With SARS, and subsequently with 2009-10 influenza A H1N1, and more recently with 2014-16 Ebola outbreaks, the early predictions far exceeded the actual number of cases and deaths. Further, with a far more difficult SARS-COV2 virus, the early predictions, even the best-case ones have proven to be quite outrageous thus far. The area under the curve was projected to include a whopping 60 per cent of the global population. A mathematical model can however only be as good as its assumptions, which relied on flawed and rather limited knowledge of the SARS-CoV2 virus early on. Interestingly, beyond the R0 and other transmission dynamics and the connectivity factor, there also seems to be a clear element of random chance in limiting the outbreak in reality, and epidemiology is largely an evolving science.
The lockdowns
Faced with a monumental challenge and without much answers, most governments hit the pause button. Aiming to contain the spread by limiting human-to-human transmission, they implemented unprecedented widespread lockdowns, choosing lives, over livelihoods and economies. Clearly, erring on the side of caution has been the guiding motto, and perhaps rightly so. This allowed governments to essentially buy time, to rapidly ramp up their health systems’ preparedness to fight the battle ahead. Aggressive RT-PCR testing coupled with contact tracing and quarantining for laboratory-confirmed cases and their contacts, have been the backbone of the containment strategy. Put simply, this would reduce the effective R0 to a target of one, delay the peak, and flatten the curve over time.
Parallelly, large-scale dedicated hospitals and critical care centres have been set-up, re-purposing existing ones and building new makeshift ones, to treat the close to 20 per cent of the moderate-to-severe COVID-19 infections. Severe shortages of PPE and other critical equipment like ventilators are being addressed through fast-tracked innovations and frantic collaborations among governments, medtech, manufacturing sector, start-ups and academia, largely at the local level, in the face of massive global supply chain disruptions.
The societies at large have meanwhile been forced to quickly embrace a behavioural reset. They say new habits are formed in 21 days. Clearly, the lockdowns, aided by mass awareness programmes, have catalysed an attitudinal shift in ways people live and work, through adoption of mindful social distancing and hygiene practices. Despite large-scale employment losses amidst economic meltdowns, and food and shelter insecurities hitting the lower BOP segments hard, the social capitals across countries have largely risen to the occasion. Health ownership can after all be an empowering tool in managing times ahead with the virus.
The timing of initiating these lockdowns to contain the disease spread and subsequent impact has emerged as the key. Italy’s delay in effecting stringent lockdowns led to indiscriminate community spread across the populous region of Lombardy, also spurred by demographic and cultural factors. Primary care physicians here continued to treat a large number of early pneumonia cases at homes, with little SARS- CoV2 testing. A restricted testing regime and severe shortages of PPE further accelerated the spread. Its health systems, with lowest critical care beds per 1,00,000 population amongst the EU nations, were quickly inundated. The case seems to be not much different with other parts of Europe and the USA. Significant local transmission seems to have already happened, and they are struggling to cope with a sudden surge of moderate-severe COVID-19 cases. India’s lockdown, on the other hand, seems to have largely succeeded in arresting the disease growth early.
However, extending the current lockdowns in the present format, is no longer a viable option. Greater economic downturns and large-scale social unrests threaten to fuel a mammoth humanitarian crisis. Besides, a sharp rise in non-COVID-19 morbidity and mortality is real and collateral damage, with these patients mostly avoiding hospital ERs, missing hemodialysis cycles, and also denied high priority elective procedures during these prolonged times. The large private health systems across the world are grappling with increased resource costs and a sharp drop in revenues, and would not sustain. The overall costs, therefore, would clearly outweigh any reasonable benefits of lockdowns, from here on. The effectiveness and the sustainability of these measures need an urgent review, so also the current surveillance approach to assess the problem extent and the impact.
The exits:
The problem extent and the preparedness are the two most critical pillars in guiding the lockdown exit strategies ahead.
The problem extent: All countries, guided by the WHO, are ramping up their RT-PCR testing capacities on a war footing at this time, as a primary means for case surveillance, and containment through contact tracing. South Korea and then Germany showed the efficacy of this approach through their early successes. Head-to-head comparison of tests per million population between countries, however, makes little practical sense, as it depends upon each country’s testing regime, roughly guided by its estimate of the disease transmission stage and the local outbreak size. At this time, the general consensus is to target extensive testing to include all symptomatic cases, resembling influenza-like illnesses.
A country’s reported case count continues to largely reflect, how many of these cases it is actually able to identify and test in a given period. That, in turn, reflects the ground implementation efficacy of the adopted testing regime. How much of testing is enough to indicate prevalence to a reasonable accuracy, given the large asymptomatic numbers, is confounding. A surrogate prevalence measure offers some practical guidance – the test positivity rate. This is the proportion of tests reported positive of the total number of tests performed, in a given timeframe. It currently varies widely between three to four per cent across Germany and India, seven per cent in Italy and a 20 per cent in the USA. The WHO recommends this rate to be less than 10 per cent, in order to consider gradual restart of economic activities.
RT-PCR Assay’s overall accuracy depends upon the genetic diversity and the rapid evolution of the virus itself, the kit’s (lowest) limit of detection linked to the viral shedding per the course in the disease, trained personnel operating these tests, and of course the test-kit quality and validation aspects. Both false positives and false negatives are therefore known. The turn-around time for the results further plays a key role in speeding up contact tracing and containment efforts. The whole approach is thus highly resource-intensive and throws up scalability and viability challenges, once significant community transmission happens, even more so in populous and limited resource settings like India. Perhaps, the outbreak use case for RT-PCRs in such viral pandemics, needs a serious review and clearer definition.
Sero-prevalence estimates through COVID-19 antibodies testing in communities, holds greater promise for effective infection surveillance. Germany, the UK and the USA’s push to democratise Point-Of-Care test-kits through pharmacy OTCs and e-tailers, could help assess the build-up of immunity, at both individual and herd levels. According to a University of Oxford study though, these rapid qualitative Point-Of-Care kits based on Lateral Flow Immunoassay (LFIA), have shown insufficient accuracy with some possibility of false negatives and need stringent validation for general public use. The more elaborate ELISA tests, however, show both high sensitivity and specificity. Meanwhile, mystery surrounding two per cent of recovered cases in South Korea and over five per cent in China, testing positive again within a little over a month, has sparked serious debate about the adequacy and duration of the protection offered by such immunity, against a possible re-infection. Therefore, stratified de-quarantining of communities and re-opening of work-places based on the ‘immunity status,’ calls for stronger evidence and caution.
Deaths are perhaps a pragmatic indicator of a country’s overall disease trajectory, and therefore the real problem extent. Official daily figures, however, exclude all those who did not die in the hospital, or who did not test positive. Reporting protocols for in-hospital deaths too, vary widely from country-to-country. These figures therefore do not indicate the real Case Fatality Rate (CFR). In many European countries and the USA, with health systems bursting at the seams, the milder symptomatic cases are clearly not being tested; whereas in other places like India, a significant number of early symptomatic patients are likely not seeking medical attention due to stigma and fear of ostracisation. Clearly, in both these cases, the numbers represent more of a ‘test’ fatality rate.
The best way to assess the impact extent is therefore to look at ‘excess mortality’ – the gap between the total number of people who die from any cause during a given period and the historical average for the same place and time of the year. This, of course, needs robust national-level statistical offices and reporting systems, and can take varying amounts of time for scrutiny. Belgium led the way in reporting the highest per capita death rate in the EU, counting almost half of its total COVID-19 deaths among the elderlies in its nursing and care homes. The data emerging from Italy, Spain, Netherlands and France suggest this gap could be in the range of 60-140 per cent (over the reported deaths) over the last few weeks. By carefully expanding the COVID-19 death definition and analysing death certificates retrospectively, England and Wales and also, New York in the USA also seem to be getting closer to the real disease impact on their populations. On the other hand, Germany and also India continue to audit deaths only in laboratory-confirmed cases. Coupled with sero-prevalence assessment, death surveillance can lead to true infection fatality rates in days ahead.
Preparedness: Hospital data and outcome indicators, such as hospital admission numbers, those requiring supplemental oxygen, critical care, ventilatory support and discharges showing recovery rates, as well as death numbers, are great pointers to the disease impact on a given population. These, along with average turn-around times for hospital and especially critical care beds, indicate a country’s expanded health system’s capacity to effectively mount a response – its preparedness levels. The ramped-up testing, tracing and containment capacities continue to be another key determinant of effective case surveillance. Targeted random testing across emerging hot-spots, and perhaps non- uniform sampling, directed at more vulnerable population sub-sets, is likely to provide a more accurate and close approximation of true infection prevalence. Further, a country’s clinical research and life sciences capabilities boost local evidence on disease pathophysiology and effective treatment protocols, like convalescent plasma. These positively impact outcomes over time.
The digital push: COVID-19 has greatly catalysed the digital transformation of legacy healthcare delivery systems globally. Huge strains on the physical systems and the need for social distancing are pushing the adoption of digital health tools. Symptom checkers and risk assessment tools offered by tele- consultation platforms, to flag potential cases early, top the list. Microsoft is collaborating with the US- CDC to run a large healthcare chatbot service, the coronavirus self-checker. Location and vitals tracking of laboratory positive cases and their contacts during quarantining through IoT solutions, is another impact area, led by Hong Kong and Taiwan earlier.
The ‘Data for Good’ initiatives by technology giants like Google, Apple and Facebook, along with multiple other government-led ones, now monitor real-time people movement patterns, and greatly boost the otherwise labour-intensive contact-tracing and containment efforts. Seamless information exchange connecting various stakeholders, policy makers, researchers, public health systems, and critically, laboratories running and reporting RT-PCRs, is at the core. The Pan-European Privacy Preserving Proximity Tracing (PEPP-PT) initiative goes a step further to define a data standards framework, to co- ordinate digital interventions across borders, while limiting purpose and addressing over-reach concerns of intrusive location tracking tools. Microsoft’s contact tracing initiative with University of Washington, CovidSafe is centered around keeping user data stored on people’s own phones, instead of a central database. However, a vast majority of smartphone-owning population, needs to voluntarily use these apps to make these solutions truly effective. Users would also always need to carry their phones, turned on, and with GPS and bluetooth enabled.
The ongoing implementation of a wide variety of national exit strategies is an unparalleled learning experiment in human history; strategies must be objectively revisited and refined on the go, as evidence unfolds. Identifying, circling and containing established ‘hot-spots’ along with those at established risk, the vulnerable populations, is a clear tactical priority, as mitigation of losses to lives and socio-economic systems takes priority ahead. A dynamic assessment of lockdown easing impacts should also guide in deciding how much mobility can be safely allowed over time, avoiding significant resurgences in the immediate future. In addition, while evolving best practices globally can serve as guiding light, localised evidence must inform effective interventions.
The smart Population Health Surveillance imperative:
The Canadian health-monitoring platform, BlueDot scoured news reports using NLP and most importantly airline ticketing data using an AI algorithm, to flag the spread of COVID-19 to Bangkok, Seoul, Taipei and Tokyo, as early as 31st December, 2019, way ahead of the WHO and the US-CDC. Taiwan, on the other hand, was the first country to flag human-to-human transmission of the SARS CoV2 virus around the same time. Having learnt hugely from the earlier SARS outbreak in 2002-03, Taiwan set up dedicated public health command centers and ramped up technology-aided surveillance and emergency response systems to help predict, prevent and mitigate losses from such outbreaks. It continues to mount an effective response and has prevented any community transmission, while avoiding stringent lockdowns.
Mounting evidence suggests a prognosis challenge in laboratory-confirmed COVID-19 cases, with sudden deterioration reported amongst otherwise stable patients, at homes and in hospitals across EU, the UK and the USA. Effective treatments and a potential vaccine still seem some time away. Besides, an infection does not seem to trigger an adequate immunity protection against a future re-infection. Therefore, case surveillance must adopt smarter tools. A robust population health surveillance system must encourage all symptomatic patients, even the milder ones, to freely come forward and test. Symptoms and vitals reporting and tracking tools, must flag potential ILI outbreaks in communities early, much before they reach the hospitals. This would boost early and targeted containment, and also mitigation of COVID-19 morbidity and mortality. A proactive ‘predict and prevent’ population health approach must replace a largely reactive catch-up response so far. Empowering people with the right tools to take ownership must take centerstage. Through sustained engagement and participation of people and communities, democracies can impact a radically different frontline battle against COVID-19 in times ahead.
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