This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.
Nine months into the coronavirus pandemic that has now killed more than one million people, global health experts have gained a clearer understanding of what has to happen to successfully contain the disease and protect populations going forward—and it’s going to require close coordination and collaboration.
They shared those hard-won lessons recently at a special, virtual gathering of international scientists and clinicians hosted by Harvard.
“Conquering this contagion will depend on unraveling the biology of the virus, understanding the pathophysiology of the disease, and developing treatments and vaccines to halt its spread,” said George Q. Daley, dean of Harvard Medical School, in his welcoming remarks at the online symposium, which focused on developing solutions to the global health crisis.
“Vanquishing COVID-19 will depend critically on how we learn from each other and how we collaborate as a global biomedical community united against this common threat,” he added.
Scientists from the HMS-led Massachusetts Consortium on Pathogen Readiness (MassCPR) in Boston, and colleagues in China, Italy and South Africa convened via teleconference on Oct. 7 to examine the impact of and response to COVID-19 in some of the early pandemic hot spots and to share lessons learned from past epidemics.
The session was part of Worldwide Week at Harvard, and it featured researchers and clinicians who have spent decades fighting some of the world’s deadly outbreaks of infectious disease.
Mark Elliott, vice provost for international affairs and the Mark Schwartz Professor of Chinese and Inner Asian History at Harvard, welcomed participants, noting that MassCPR is a historic partnership benefitting people around the world as nations join to confront COVID-19’s unprecedented threat to life, health and well-being.
In just 10 months, Daley said, the pathogen has exacted an extraordinary human toll—not only through a high mortality rate, widespread infection, and the severity of illness it has wrought but also through economic devastation and radical transformations in the way societies are socializing, working and learning.
To help put COVID-19 in context, Megan Murray, the Ronda Stryker and William Johnston Professor of Global Health in the Blavatnik Institute at Harvard Medical School and director of research at Partners In Health, shared a historical perspective from epidemics past and a current view of ongoing outbreaks.
Murray described several of the most catastrophic epidemics of infectious disease in the 20th and 21st centuries, including outbreaks of pneumonic plague among migrant hunters in Mongolia, Nipah virus among farmers and meat processing workers in Malaysia, and the ongoing series of Ebola outbreaks that have ravaged the Democratic Republic of Congo.
The common threads that bind these outbreaks, she said, are economic and ecological disruption, which put impoverished people with limited access to health care in direct contact with deadly pathogens.
Murray noted that it is not just novel pathogens that pose a particular risk: tuberculosis, like COVD-19, does not cause symptomatic disease in most of the people infected and thrives where people live in crowded conditions with poor ventilation, indoor air pollution and comorbidities of chronic diseases associated with poverty.
The lesson for the current coronavirus pandemic is that these social and environmental forces need to be taken into account when confronting an outbreak, she said.
“Epidemics expose the fault lines of our society, and we cannot address them without seeing and trying to mend the fissures in our society,” Murray said.
Awareness of the social, cultural and political context of the disease outbreak is an important element in the way the pandemic plays out around the globe, both in terms of how the illness is transmitted and in terms of how it is treated and controlled, noted Paul Farmer, the Kolokotrones University Professor of Global Health and Social Medicine, head of the department of global health and social medicine at HMS, and co-founder of Partners In Health.
“We need to look at pathogens, of course, which have different modes of transmission,” he said. “We also need to understand pathogenic forces that drive transmission in overcrowded hospitals and meat packing plants.”
Farmer said that two key takeaways from his decades of experience confronting tuberculosis, HIV, Ebola and other pandemics around the world is that the global medical community needs to understand two deadly concepts: treatment nihilism and containment nihilism.
Treatment nihilism occurs when someone says it’s not feasible or sustainable to treat someone for a particular disease, typically people who are poor or in rural areas facing complex diseases, Farmer said. It explains why so many Ebola treatment units did not offer any treatment for people with Ebola in the 2014-2016 outbreak in West Africa. Containment nihilism is when someone says it’s too challenging or too late to control the spread of a disease.
COVID-19 case studies from China, Italy and South Africa highlighted during the symposium demonstrated the critical importance of ramping up treatment capacity while also controlling the transmission of the disease through social distancing, mask wearing and eliminating large gatherings.
In the COVID-19 pandemic in the United States, however, Farmer said there have been early and ongoing declarations from government leaders at the local and national level that it was too late or too challenging to contain the disease or do contact tracing.
This was a key element in the “substantial failure at disease control in the U.S.,” he said.
“In April, people had already given up on contact tracing,” Farmer said.
At that time, Partners In Health was contracted by the Commonwealth of Massachusetts to provide assistance with contact tracing and social support to help individuals who were exposed or infected and were in isolation or quarantine.
Farmer said he believed that the expanded contact tracing effort Harvard and PIH were able to support likely played a role in helping Massachusetts maintain infection rates at lower levels than in many other states which were experiencing a rise in infection rates.
With COVID-19 now hitting the White House, Farmer said, there is no sign of any contact tracing being done to follow the spread of the outbreak into the communities of Washington, D.C., and beyond.
“This is a real problem, since experience has shown us that contact tracing should play a role in curbing the pandemic,” Farmer said.
Nanshan Zhong, professor of respiratory medicine at Guangzhou Medical University and director of the Chinese National Clinical Research Center for Respiratory Disease, was introduced by Daley as the “legendary physician-scientist” who discovered the first SARS virus and who has led the Chinese response to both SARS and SARS-CoV-2.
Zhong detailed the early response and evolving dynamics of the infection in China, describing the rapid recognition, characterization and response to the novel coronavirus when it first emerged in Wuhan.
The first cluster of pneumonia was reported Dec. 27, 2019, and by early January 2020, Chinese scientists had already sequenced the genome of the virus, sharing the information with the World Health Organization by Jan. 12, he said.
Following a rapid, thorough investigation of the outbreak, Zhong said the team on the ground in Wuhan reported definite human-to-human transmission and confirmed, within weeks of the first known cases, that medical staff there had been infected while treating people with the virus.
By Jan. 23, Wuhan was under lockdown; the government was providing real time announcements of the number of patients affected, and it was implementing a program of early diagnosis, early isolation and early treatment.
The Chinese government also issued orders for compulsory social distancing, mask wearing and travel restrictions in an effort to quickly contain the disease, he said, and it swiftly constructed 16 hospitals within 19 days that added 13,000 hospital beds to the local capacity, rapidly filling 12,000 of those beds.
That speedy response to contain and treat the disease helped drive a prompt decrease in cases, he said. Within two weeks of the shutdown order, Zhong said, the outbreak reached its peak. Within four weeks, he said, the outbreak was basically under control.
Since then, the outbreak has remained quite stable inside China, with low levels of infection, Zhong said. The total number of reported cases in China was 80,000 by March 1 and was just over 91,000 as of Oct. 5. The 11,000 cases reported since March 1 includes 3,000 cases brought into China by visitors from outside the country, Zhong said.
Because of the country’s swift, coordinated action, China was able to reduce infections and illness and reopen the economy sooner, Zhong said. Going forward, he added, a strategy of prevention remains crucial until vaccines can be brought online.
Herd immunity through natural infection would likely result in 30 million additional deaths, he noted. Meanwhile, even with a dozen vaccines already in various phases of the clinical trial process around the world, it will likely take 1-2 years, even with global collaboration, for vaccines to be widely available to the general public, he said.
Strong, coordinated action by central governments to help block transmission routes at the community level is still the most effective means for disease control, Zhong said.
“There is also an urgent need for close international collaboration in tracing sources of new outbreaks, developing targeted treatment and finding effective vaccines,” he said.
The African picture
Salim Abdool Karim, professor of global health at Columbia University Mailman School of Public Health and adjunct professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, said that, to date, Africa has seen many fewer cases and deaths from COVID-19 than expected, with 1.5 million cases and 36,000 deaths for the entire continent.
So far, the disease has been particularly concentrated in just a few African countries. South Africa alone represents nearly 40 percent of cases, with five nations on the continent accounting for two-thirds of all cases in Africa, he said,
He noted that while many African countries lack sufficient testing and reporting capabilities to gain a completely accurate picture of the spread of the virus on the continent, hospital surveillance confirms that there has not been a great increase in severe cases of respiratory disease there.
There is still no definitive evidence to explain why Africa has been less severely impacted than other regions, he said, but Karim noted that many suspect it may be related to Africa’s youth dividend, referring to the fact that Africa has a much younger population on average than other places that have seen higher rates of infection and severe disease.
Other possible explanations include the fact that there seem to have been few initial cases seeded before international and local travel were limited by early lockdowns, said Karim, a member of the Africa Task Force for Novel Coronavirus of the Africa Centers for Disease Control and Prevention.
He also noted that there has been a strong, consistent commitment among the nations of the African union to control the outbreak, with strong guidance and a coordinated response led by the recently created Africa CDC. That included bulk procurement of testing supplies and personal protective equipment and early adoption of mask wearing and social distancing.
South Africa had some of the first reported cases on the continent in early March, but instead of seeing a rapid spike, the country was able to quickly get the outbreak under control following a rapid declaration of a national state of disaster and a highly restrictive shutdown, he said.
The early flattening of the curve brought a great deal of economic hardship, according to Karim, but the rapid shutdown bought the health system the time that it needed before cases surged.
“If the peak had occurred in April, we would have had lots of death because we were simply not prepared,” Karim said. “Pushing the peak back allowed us to prepare.”
South African health officials opened field hospitals with hundreds of ICU beds, and the government redirected industrial oxygen to medical purposes. Building on experience from nations that faced the surge earlier, physicians there replaced mechanical ventilation with less invasive means of delivering oxygen to patients in respiratory distress.
One important element of African efforts to control spread of the virus was a shift of responsibility from government control to individual engagement, Karim said.
“We knew he had to pivot away from government action quickly so that people could take agency,” he said.
The early emphasis on shutdowns and travel restrictions was replaced with an emphasis on mask wearing, social distance and hand hygiene. Education and awareness efforts focused on the individual’s shared responsibility to their fellow community members.
The message was, “If you don't follow the rules, you put everyone at risk,” Karim said, drawing on the concept of ubuntu, a paradigm and social norm instilled by former South African President Nelson Mandela in much of South African society, Karim said.
Ubuntu holds “I am safe, because you are safe,” he said.
“Our collective interdependence is the basis on which we will protect ourselves going forward,” he said.
One other key concept is perseverance, he said. With the relaxation of restrictions, the levels of infection have begun to climb slowly, but Karim emphasized that the country’s efforts will not be over even when COVID-19 is under control.
“We’re not looking at it as a sprint, as we did in March,” he said. “Now we’re looking at it as a marathon.”
“We've seen other epidemics, and we will see more,” he said. “We recognize that we're going to have to deal with this for a long time. This is not something that is just going to go away.”
The Italian wave
Fabio Ciceri, scientific director of the San Raffaele Scientific Institute and professor of hematology at Vita-Salute San Raffaele University in Milan, shared his insights from the early days of the pandemic in northern Italy and its evolving nature there today.
When COVID-19 hit northern Italy, the novel coronavirus was still almost completely unknown, he said.
“We were the first country in Europe touched by the wave,” Ciceri said.
Centrally coordinated regional and national responses helped get the outbreak under control relatively rapidly, he said, with national shutdowns and care coordination that focused 80 percent of national health care resources on beating back the novel coronavirus.
Even in the early days of the outbreak, Ciceri said, his team made an extra effort to collect biological samples and clinical data to be used for important research activities, with scientists carefully analyzing the results of numerous potential treatments and enrolling many patients in clinical trials.
These early efforts to incorporate research into care delivery are now providing Italy’s scientists with the raw materials necessary to power biological studies of the virus’s pathology and detail the immune system’s response to the infection. Ciceri said this approach helped Italy rapidly lower mortality rates in the early surge.
As clinicians developed new protocols for rapid, aggressive early intervention in potentially serious cases, fewer patients needed to be admitted to hospitals, fewer of those who were admitted needed intensive care, and fewer patients died, he said. Mortality rates for those admitted dropped from 25 percent to 2 percent, he said.
Going forward, Italy has increased early testing and contact tracing of new positive cases and built connections between hospitals across the country to share experience and care, focusing on early interventions for patients with symptomatic disease and referrals to special COVID-19 hubs for patients who might benefit from new treatments and investigational trials.
Daley said the advance warning and the generous flow of clinical and scientific knowledge from colleagues in China and northern Italy was of “incalculable value.”
“They provided us with ample warning about the hurricane headed our way, enabling us here in New England to prepare for the surge and avert catastrophic overload of our hospital systems,” Daley said.
“Unfortunately,” he said, “the U.S. failed to mount a coordinated national effort and some parts of our country did not heed the early warnings from abroad—choosing instead to ignore the very public health measures that had worked to ultimately bring the explosive virus under control in the early epicenters of the pandemic. To this day the U.S. continues to struggle to contain the virus, and the death toll continues to mount.”