World is Entering a ‘New and Dangerous Phase’ of the Pandemic, WHO
Period. 14 – 21 July 2020
World is Entering a ‘New and Dangerous Phase’ of the Pandemic, WHO
- During its Monday media briefing, the WHO Director General outlined four types of COVID-19 outbreaks occurring globally, including countries that [1] responded rapidly and avoided large outbreaks, [2] brought large outbreaks under control, [3] overcame their first peak and are struggling with new peaks, and [4] are currently in the intense transmission phase. The last category presents the biggest immediate risk and includes ten countries that account for almost 80% of new infections, with half of these in the U.S. and Brazil alone. The rate of new infections in the U.S. does not appear to be slowing despite an increase in testing, with total cases expected to surpass 4 million this week. With over 2 million confirmed cases, the outbreak in Brazil continues to be a major concern, particularly in light of irregularities in official government figures. This led to a stand-off last month between Brazilian President Bolsonaro– who has been criticized for downplaying the pandemic despite testing positive for the virus last week – and the Supreme Court, which prompted one Justice to demand the government immediately “re-establish the daily dissemination of epidemiological data on the COVID-19 pandemic.”
- The Red Cross Red Crescent has warned that South Asia is quickly becoming the next epicentre of the pandemic, with rapidly rising cases across India, Pakistan, Bangladesh and Afghanistan. With the second highest number of daily new cases and over 1.1 million confirmed infections, the outbreak in India is rapidly escalating. This includes the Delhi metropolitan area that is home to 25 million people and accounts for almost half of all cases in the country. The latest projection from MIT, still under peer review, warns that India could have the largest number of cases in the next six months, with modelling scenarios estimating up to 287,000 cases per day in the absence of stronger public health measures.
- Across Africa, the number of COVID-19 infections surpassed 750,000 this week, as the over 15,000 mortalities over the past five months have now exceeded the total number of lives lost to the West African Ebola outbreak between 2014 and 2016. At least 22 African countries have seen the number of Coronavirus cases double in the last month, with at least 35 countries experiencing community transmission. With the largest number of cases on the continent, South Africa recently re-imposed a ban on the sale of alcohol to reduce avoidable injuries and the burden on hospitals, while tightening curfews and mask requirements. Fragile health systems in many countries on the continent are increasingly overwhelmed, according to the WHO Director for Africa, who called on governments and the international community to scale up public health measures such as testing, contact tracing and case isolation. There is particular fear of outbreaks among vulnerable populations such as humanitarian response locations, marginalized communities as well as elderly populations, who are on average ten times more at risk of death, although they only account for 20% of COVID-19 infections in Africa.
- Countries that previously succeeded in containing the virus are meanwhile reporting resurgence in cases, such as Hong Kong where a third wave of outbreaks prompted renewed lockdowns and physical distancing measures. A paper in the BMJ shows how COVID-19 related mortalities in Mexico have also tripled since the country began to relax lockdowns in early June despite warnings by experts and local health officials questioning official figures by the government. The cost of a subsequent lockdown in OECD countries alone has been estimated at US$1.1 trillion in additional output losses this year, which would increase five-fold if an outbreak were to occur in early 2021.
The Cost of Doing Nothing: Estimating the Impact of Inaction on COVID-19
- The Centre for Global Development published a study this week providing a comprehensive taxonomy of direct and indirect costs associated with failure to act proactively in containing the spread of the Coronavirus and mitigating its cascading effects. These can include direct and spill-overs health care costs, such as disruptions and resource diversion (with one study estimating two million additional deaths due to HIV, TB and Malaria alone). The human and economic costs associated with increased poverty have also been unprecedented, with the latest biennial World Bank Global Economic Prospects estimating the biggest collapse in per capita GDP in over 150 years. The two billion informal workers are expected to be impacted most severely, with 80% already affected by pandemic containment measures. Protracted school shutdowns will also generate learning losses estimated at $10 trillion globally, while a study by Oxford highlights the risk of outbreaks across 63 fragile countries, with 13 additional states projected to experience new conflicts over the next two years. Based on present and anticipated human and economic costs, the CGD study argues frontloading responses to COVID-19 and its secondary effects would not only cost exponentially less but would also be more dignified for people globally.
- The unorthodox approach Sweden initially adopted of virtually ignoring COVID-19 has since become the cautionary tale. Unlike the rest of Europe, the country resisted lockdowns and physical distancing measures for economic reasons, gambling instead on herd immunity. The result three months later has been significantly higher cases as well as 12 times higher mortality rates than neighbouring Norway, while a much slower projected economic recovery. An analysis by Peterson Institute for International Economics affirms Sweden “literally gained nothing” from what they describe as a “self-inflicted wound.”
International Coordination is Essential to Avoid Resurgence
- A new study in Science demonstrates the need for a coordinated approach for countries in Europe to lift lockdown measures in order to prevent subsequent outbreaks of cases. The research team from WorldPop highlight the significant impact of actions by countries that are populous, well-connected and with strong interventionsin place – which include France, Germany, Italy, Poland and the UK. The study produced over 1,200 exit strategy scenarios, using publicly available epidemiological data as well as anonymized mobile phone data to map population movement in 35 European countries. A notable finding of the study is that premature and uncoordinated easing of control measures by some countries could accelerate the resurgence of COVID-19 outbreaks across the entire continent by up to five weeks. The simulations furthermore show that synchronizing intermittent lockdowns across countries would lead to half as many necessary lockdown periods in order to achieve an end to community transmission in six months.
‘Myths, Delusions, and Falsehoods’ of Progress on Equality, UN Chief
- During the Sustainable Development Goals progress review meeting over the weekend, the UN Secretary General issued one of his strongest rebukes of the international community for systemic inequities that the COVID-19 pandemic has exposed. In a significant departure from his traditional diplomatic tone, the Mandela Day speech by the UN head noted the many “myths, delusions, and falsehoods” around international progress on equality. Among the examples he listed was the “lie that free markets can deliver healthcare for all. The fiction that unpaid care work is not work, the delusion that we live in a post-racist world, the myth that we are all in the same boat.” He went on to call for a “New Social Contract” with commitment of renewed and inclusive multilateralism, while urging for fundamental reforms to the UN Security Council, the IMF, and the World Bank.
- Humanitarian response locations remain a particular cause for concern, including in sub-Saharan Africa which is home to over 26% of the world’s refugees. Ongoing conflicts and persistent attacks have led to the closure of hundreds of health facilities, including in Mali and Burkina Faso where 1.5 million people are left without adequate health care. During its Monday media briefing, the WHO cited a recent study by Oxford University highlights the risk of conflict on outbreaks, identifying 63 fragile countries currently facing unrest and conflict in the background of the COVID-19 pandemic, while additional 13 countries are projected to experience new conflicts over the next two years. The study further estimates that the average cost to host and neighbouring countries for a civil war is about $60 billion, while 100 million could be pushed into extreme poverty and 130 million face starvation.
International Pandemic Response ‘Grossly inadequate and dangerously short-sighted’
- The UN released an updated COVID-19 Global Humanitarian Response Plan, doubling its appeal to $10.3 billion, more than 80% of which would support responses in 63 low-income countries. Another $1.8 billion would be directed for ‘global requirements’, transport of aid workers and supplies accounting for $1 billion, with a further $300 million allocated directly for NGOs and $500 million for 25 ‘hotspots’ most at risk of famine. The UN Emergency Response Coordinatorwent on to warn that the pandemic and the associated global recession are about to wreak havoc in fragile states, while describe the response by wealthier countries as “grossly inadequate and dangerously short-sighted.”
- The timely and directed appeal comes as G20 Finance Ministers and heads of central banks are set to meet virtually this coming Saturday. An estimated $11 trillion in stimulus packages have been appropriated by G20 countries as part of an unprecedented economic response, representing 10% of global GDP. To protect the most vulnerable 10% of the world across 32 low-income countries would meanwhile cost less than $90 billion, which is less than 1% of domestic stimulus packages by wealthier countries. The UN Emergency Response Coordinator contrasted the solidarity and international coordination in the aftermath of the 2008 Global Financial Crisis, particularly highlighting the need to reinforce and reassert the role of the IMF and World Bank in supporting lower income countries.
COVID-19 is Pushing Countries ‘Closer to the Abyss’ of Famine, WFP
- The World Food Programme has identified 25 ‘hotspots’ where acute hunger is reached devastating levels. Most of the countries stretch between West and East Africa, while vulnerable populations in Latin American and Middle Eastern countries, where the pandemic has exacerbated income losses, disrupted supply chains that contributed to surging food prices. The WFP and FAO previously estimated that food security could increase by 81% this year to almost 270 million people. Every 1% rise in acute hunger also contributes to a 2% increase in refugee outflows, which further threaten vulnerable populations as well as regional stability. The UN released an updated COVID-19 Global Humanitarian Response Plan last week, with the $4.9 billion WFP response accounting for nearly half of the sum, and an additional $500 million special provision for the 25 hotspots most at risk of famine.
- A new study in PLoS Medicine shows that combining severe and moderate acute malnutrition treatments into a simplified protocol could be as effective as traditional treatment while saving $123 per child. The ‘Combined Protocol for Acute Malnutrition Study’ was conducted by LSHTM, the International Rescue Committee and Action Against Hunger, and found that the combined protocol was 76.3% effective at promoting nutritional recovery, which is slightly better than the 73.5% for standard treatment. With 50 million children currently not receiving malnutrition treatment, the efficacy and cost savings could translate into program expansions, with three million child deaths a year are linked to malnutrition.
Questions Persist on Immunity to COVID-19
- During Monday’s media briefing, the WHO Technical Lead for COVID-19 suggested that while those who are infected with the novel Coronavirus did mount some level of immunity, there are persistent uncertainties how strong that protection is and for long it lasts. This came a day after a study by King’s College London found that immunity appeared to peak three weeks after the first symptoms, waning rapidly thereafter. The study, which is currently under peer review, shows that 60% of people had a “potent” antibody response at the height of their infection, but that only 17% retained the same potency three months later, while others had undetectable antibody levels. This is corroborated by other studies that suggest loss of immunity within a couple months after infection, which if true could challenge the notion of herd immunity to COVID-19.
- A paper in Nature Medicine this week meanwhile provides a detailed survey of the immune response in a cohort of COVID-19 patients to the Spike antigen by memory B cells and T cells. In addition to coordinating and controlling antibody responses, T cells can also detect fragments of a virus (peptides) which makes it harder to dodge immune defences. Although the study only included a small number of adults with mild infections, both could be detected in the blood one month after COVID-19 infection, suggesting key protective immune responses could be generated in natural infection and may be potentially boosted.
- These results could have important implications for vaccine development, as certified antibody diagnostic tests are currently designed to detect one single antibody response, and not to quantify it. Consistent and sustained levels of antibody response, however, may require annual booster immunization, similar to the seasonal flu vaccine. According to the Nature Medicine paper, the most effective vaccine against COVID-19 is likely to elicit both neutralizing antibodies, as well as a high total antibody titre and strong T cell response. While immunological questions persist, the WHO warned that it remains possible that people may be re-infected, urging safe public health measures.
High Accuracy Shows Promise of Rapid Fingerprick Antibody Testing
- Rapid and non-invasive antibody diagnostics remain a holy grail in scaling up testing for COVID-19. Preliminary results are currently under peer review for the rapid finger prick antibody test, AbC-19 Lateral Flow, that claims to be 98.6% accurate. While these claims seem promising, the results have not been made public, with questions remaining on the sets of samples the study used or what the researchers mean by ‘accuracy’. Diagnostic tests are typically assessed by sensitivity (false negative) and specificity (false positive). The other outstanding issue with these types of tests, however, relate to uncertainties in the period of time after infection that IgG antibodies disappear from the blood. Since acuity of COVID-19 infection appears to be correlated with the intensity of the antibody response, it is plausible that the test could come back negative for those with low antibody levels in as little as three months (for reference, antibody levels for SARS were detectable for up to two years). A rapid antibody test would nonetheless be a valuable diagnostic tool for detecting positive cases, even if negative test results would require further investigation. It is also important to note that other human coronaviruses don’t confer lifelong immunity, while ongoing research is also examining the role of T-cell immunity.
Early Vaccine Trials Show Encouraging Results
- Over 150 efforts are currently underway around the world to develop COVID-19 vaccines and therapeutics, according to the WHO, with 23 vaccine candidates currently in human trials. Most of these studies are in Phase 1 trials that typically include a small number of healthy people where the goal is to determine safety and whether an immune response is observed. A small number of Phase 2 trials are also underway that include a larger and more diverse population, while none of the vaccine candidates have entered Phase 3 trials that focus on balancing efficacy (i.e. vaccine dosage to elicit immune response against SARS-Cov-2) and safety (i.e. minimizing adverse side effects). A number of papers over the past week reported on promising developments in three leading vaccine trials currently underway in the U.S., the U.K. and China.
- A paper in the New England Journal of Medicine last week shows encouraging interim results for Moderna’s mRNA-1273 that targets the “spike” protein used by SARS-Cov-2 to enter cells. The Phase 1 clinical trials conducted by the U.S. National Institutes of Health confirmed that 45 health adults who received two doses of the vaccine 28 days apart had higher levels of antibodies than those who had recovered from being infected by COVID-19 (with the peak in antibody production coming only after the second dose). Moderna will begin Phase 2 trials on July 27, while mRNA-1273 is also expected to be the first vaccine candidate to enter Phase 3 efficacy trials later this year, with efforts underway to recruit over 30,000 people.
- The Lancet this week also published encouraging results for another leading vaccine candidate from the U.K., AZD1222, developed by Oxford University and AstraZeneca. The interim findings show the vaccine continues to induce antibody and T-Cell immune responses up to day 56 of the ongoing Phase 1/2 trials that involve 1,077 health adults. A sub-group study of 10 patients receiving a second dose showed an even greater immune response to SARS-Cov-2. While no major adverse events were observed, 60% of patients did report mild side effects (fever, headaches, muscle aches, and injection site reactions) compared to the control group, a meningitis vaccine. AZD1222 is expected to advance to Phase 2 trials this month of a diverse patient population.
- A research team from China also published results in the Lancet this week on Phase 2 trials for a vaccine candidate developed by CanSino. The latest findings validate previous Phase 1 data that show the vaccine induces an immune response to SARS-Cov-2, but that the neutralizing antibody response is not as strong in some key demographics, including people over the age of 55.
- While these early results are promising, Merck’s CEO in the Harvard Business Review claimed it would be a “great disservice” to raise hopes that a vaccine would be available to the public by the end of the year. Novel vaccines often take years or decades to develop, due to established research protocols to ensure safety and efficacy. Vaccines also present unique manufacturing and distribution challenges that often limit production capacity while requiring complex logistical efforts. This is further strained by the global demand for a COVID-19 vaccine, as civil society groups have urged the international community to establish vaccine distribution agreements to prevent hoarding by wealthier countries.
- The WHOhas confirmed that 165 countries representing 60% of the world’s population have engaged in COVAX, the COVID-19 vaccine global access facility that is designed to promote rapid, fair and equitable access. As part of the mechanism, 75 countries would finance the vaccines using domestic budgets, while partnering with up to 90 lower income countries that would be supported through voluntary donations to the COVAX Advance Market Commitment coordinated by GAVI. Other regions like PAHO announced parallel pooled procurement plans to ensure countries receive vaccines at subsidized, affordable prices.