Questions about the genealogical imprint of tumors have hovered over cancer research since the completion of the Human Genome Project in 2003. Is liver cancer different at a basic, molecular level in people of African descent than people of European descent? Does breast cancer have a different genetic profile in East Asians than Native Americans?

A new paper by researchers from the NCI Cancer Genome Analysis Network, a collaborative group with investigators in the U.S., Canada, and Europe, provides the most comprehensive look to date at the effect of ancestry on the molecular makeup of normal and cancerous tissues. Drawing on data from The Cancer Genome Atlas (TCGA) involving 10,678 patients and 33 cancer types, the investigators found that ancestry was tied to variations in hundreds of genes, but that the most important of these differences were linked to specific tissue types. The study is being published online today by Cancer Cell.

“We found that in patients of different ancestries, the molecular features corresponding to those differences were largely confined to specific organs and tissue types,” said Rameen Beroukhim of Dana-Farber and the Broad Institute, the co-senior author of the study with Andrew Cherniack, group leader at Dana-Farber and the Broad Institute. “This suggests that tracking the molecular effects of ancestry — both in normal and cancer tissue — needs to take a tissue-by-tissue approach.”

Among the researchers’ specific findings:

• From a molecular standpoint, people of African ancestry tend to have a different type of kidney cancer than people of European ancestry. The African variety is marked less often by mutations that disable the VHL gene, spurring the growth of new blood vessels for tumors.
• Bladder cancers in people of East Asian extraction show fewer signs of drawing an immune system response than bladder tumors in people of European background.

In the study, investigators used a variety of molecular techniques to determine the ancestry of the patients whose tissue samples were analyzed. Patients were classified as being primarily of European, East Asian, African, Native/Latin American, or South Asian descent. Patients whose ancestry was at least 20 percent mixed were classified as being of admixed descent. (These patients were subcategorized by their primary ancestry, such as African-Admixed, European-Admixed, etc.) As a group, the patients had 33 cancer types, 13 of which were further divided into subtypes.

TCGA had conducted a deep analysis of each patient’s tissue, testing cancerous and normal cells for a range of molecular features. These included mutations (miscopied sections of DNA); patterns of DNA methylation (a process that influences whether genes are switched on or off); messenger RNA (a molecule that carries a transcribed version of DNA and is indicative of gene activity); and microRNA (a form of RNA that assists or hampers gene activity). The NCI Cancer Genome Analysis Network investigators used this data to see whether differences in any of these features reflected differences in ancestry.

“We found that ancestry-associated differences spanned all of these features and were present in hundreds of different genes,” Cherniack stated. “It turned out, though, that the most significant differences — the ones that affect how cells function and interact with the rest of the body — were profoundly tissue-specific.” Although ancestry affected molecular features in most cancer types, these effects were not shared across cancer types. Molecular differences in lung cancers that were traceable to African ancestry, for example, were not found in breast, pancreatic, or other cancers.

The data also enabled investigators to ask whether the ancestry-related features of normal cells carried over into the cancerous versions of those cells — whether the molecular particularities of lung cells in people of European extraction for example, are also found in the lung cancer cells of such individuals. They found that this was overwhelmingly the case. “Most of the differences in the normal tissues of people with specific ancestries are recapitulated in cancer,” Beroukhim stated. Moreover, evidence suggests that some of these differences may contribute to the development of certain cancers in people with similar backgrounds.

Having access to data from patients of mixed lineage proved to be an asset, the study authors say. Investigators conducted their initial analysis in patients whose ancestry was at least 80 percent within one of the five genealogical groups. They followed this with a similar analysis of data from the admixed populations. “When the results of the two analyses jibed — when molecular differences specific to one ancestral group also appear in patients whose ancestry is a combination of that group and others — it was particularly strong evidence of the validity of the original finding.” said one of the study’s co-lead authors, Jian Carrot-Zhang, postdoctoral research fellow of the Meyerson group at Dana-Farber and the Broad. “The patients of mixed background were a particularly powerful group in which to study the molecular effects of ancestry in cancer,” Beroukhim stated. “It helped us narrow down which regions of the genome contribute to these differences.”

The comprehensive nature of the study revealed some of the shortcomings of previous efforts to link ethnicity and ancestry to molecular elements of cells. For one, such studies tended to lump various subtypes of cancer together, Beroukhim said, despite the fact that certain subtypes are more common in certain ancestries than others. Some of the techniques used to dissect molecular features may also have skewed the results of previous studies.

Researchers have yet to determine whether the molecular differences between ancestries result from environmental factors or genetic factors. However, they did identify genetic differences between ancestries that could explain many of their findings.

“Our findings point to a need for more samples from diverse ancestries to conduct a truly comprehensive ancestry analysis, especially of normal tissues,” Beroukhim remarks. “This study represents an important step in that direction.”

Funding for the study was provided by the National Cancer Institute (U24 grants CA210999, CA210974, CA211006, CA210949, CA210978, CA210952, CA210989, CA210957, CA210990, CA211000, CA210950, CA210969, CA210988, and K24CA169004 and R01CA1845851).

The Ash Center for Democratic Governance and Innovation sat down with Katharine Robb, a postdoctoral research fellow at the center’s Bloomberg Harvard City Leadership Initiative where she has been conducting research on housing and health in Chelsea, Mass. This densely populated city adjacent to Boston has seen some of the worst COVID-19 infection rates in the state. Robb completed her doctorate in public health degree at the Harvard T.H. Chan School of Public Health in 2019.

While pursuing her doctorate, Robb worked as an Innovation Field Lab fellow in Chelsea, ultimately focusing her dissertation on her work with the field lab, where she developed and implemented a novel social-service referral program within the city’s Inspectional Services Department. The program leverages the unique role of housing inspectors to link at-risk residents with services to prevent problem properties and social and health crises.

Q&A

Katharine Robb

Ash Center: Were you at all surprised that Chelsea has become one of the centers of the COVID-19 outbreak in Massachusetts?

Robb: No, it’s not a surprise. We know that diseases of many kinds disproportionately impact poor communities, people of color, and people living in overcrowded conditions. Chelsea has all three of these. Having spent a great deal of time in Chelsea, I know first-hand the strength and vibrancy of its community and culture. But, not only does Chelsea have a population with a lot of risk factors for infection, but because of the density and housing conditions, there are also limitations on people’s ability to reduce their risk from infection.

Ash Center: How do housing conditions impact health outcomes in urban environments?

Robb: Housing is so much more than physical shelter. It impacts every aspect of our lives, including our health in a really powerful way. It also impacts our security, our personal relationships, our privacy, and access to community resources. Housing related risks can stem from physical aspects of the home environment such as insect infestations that cause asthma attacks, or from financial aspects that result in poor property maintenance and create unsafe conditions in the home. Overcrowded conditions may strain interpersonal relationships or contribute to abuse or mental health problems.

Ash Center: Specifically, how have housing conditions in Chelsea possibly exacerbated the spread of the virus?

Robb: Even before the pandemic, homes were not a safe place for many residents in the city. Chelsea is the most densely populated city in Massachusetts, and one of the densest in the country. Many of the homes in Chelsea are two bedrooms or fewer, and contrary to national trends, family size in Chelsea is actually growing — so the housing stock really doesn’t match the needs of the current population in the city.

Chelsea is also emblematic of the affordable housing crisis that’s facing many cities where skyrocketing rents and stagnant wages increase the proportion of residents who lack adequate housing. Residents often cope with this by doubling or tripling up with other families and living in some really inhumane conditions such as unfinished basements or closets or porches, often lacking adequate water, sanitation, ventilation or heat. Many are forced to share bathrooms or kitchens with other families or residents, making social distancing and proper sanitary practices difficult if not impossible in some situations. Finally, we’ve seen that many Chelsea residents living in overcrowded or substandard conditions are more likely to experience underlying health conditions due to poverty, reduced access to healthcare and food, and psychological stress — which put them at greater risk of infection

Ash Center: How have past pandemics historically shaped housing policy in cities, and is there a possibility that the crisis we’re in now may spark similar changes in the future?

Robb: I think this pandemic highlights how in some communities across the US, families still face many health and social challenges — think poor ventilation, overcrowding, inadequate access to sanitation — that were faced at the end of the 19th century — and are still associated today with higher rates of death and disease. History shows us that epidemics can be a real turning point in the ways that cities address health. One hundred fifty years ago it was epidemics such as cholera or tuberculosis that generated the political will to care about improving conditions among the urban poor. This was because more enfranchised or wealthier classes were also impacted, and this gave rise to publicly financed improvements in drinking water supplies, in sanitation, as well as building and housing codes to improve sanitary and health conditions.

As the 20th century progressed the health conditions changed and we saw dramatic reductions in mortality and morbidity in cities. Over the last 100 years, the wealthy were better able to isolate themselves from unsafe or unsanitary conditions in poor areas of cities. As a consequence, budgets for public health departments shrank, and there was less political will to continue to care about the health conditions among the poor. But pandemics like this really expose so many underlying vulnerabilities and shine a light on the unacceptable disparities within our communities. It’s my hope that the pandemic can really be a turning point once again, and a call for action for greater investment in improving conditions so that members of our community are no longer living without safe and sanitary shelter.

This interview has been edited for length and clarity.

People who attended religious services at least once a week were significantly less likely to die from “deaths of despair,” including deaths related to suicide, drug overdose, and alcohol poisoning, according to new research led by Harvard T.H. Chan School of Public Health. The study showed that the association between service attendance and lower risk of deaths from despair was somewhat stronger for women than for men.

“Despair is something that can confront anyone dealing with severe difficulties or loss. While the term ‘deaths of despair’ was originally coined in the context of working class Americans struggling with unemployment, it is a phenomenon that is relevant more broadly, such as to the health care professionals in our study who may be struggling with excessive demands and burnout, or to anyone facing loss. As such, we need to look for important community resources that can protect against it,” said Tyler VanderWeele, John L. Loeb and Frances Lehman Loeb Professor of Epidemiology at Harvard Chan School. VanderWeele is also director of the Human Flourishing Program and co-director of the Initiative on Health, Religion and Spirituality at Harvard University.

The study was published online today in JAMA Psychiatry.

Religion may be a social determinant of health, and previous research has shown that attending religious services may be associated with a lower risk of various factors related to despair, including heavy drinking, substance misuse, and suicidality.

For this study, researchers analyzed data from the Nurses’ Health Study II on 66,492 women as well as data from the Health Professionals Follow-Up Study on 43,141 men. Among the women, there were 75 deaths from despair: 43 suicides, 20 deaths from poisoning, and 12 deaths from liver disease and cirrhosis. Among the men there were 306 deaths from despair: 197 suicides, 6 deaths from poisoning, and 103 deaths from liver diseases and cirrhosis.

After adjusting for numerous variables, the study showed that women who attended services at least once per week had a 68 percent lower risk of death from despair compared to those never attending services. Men who attended services at least once per week had a 33 percent lower risk of death from despair.

The study authors noted that religious participation may serve as an important antidote to despair and an asset for sustaining a sense of hope and meaning. They also wrote that religion may be associated with strengthened psychosocial resilience by fostering a sense of peace and positive outlook, and promoting social connectedness.

“These results are perhaps especially striking amidst the present COVID-19 pandemic,” said Ying Chen, research associate and data scientist at the Human Flourishing Program at Harvard’s Institute for Quantitative Social Science, and first author of the paper. “They are striking in part because clinicians are facing such extreme work demands and difficult conditions, and in part because many religious services have been suspended. We need to think what might be done to extend help to those at risk for despair.”

Other authors from Harvard Chan School include Howard Koh and Ichiro Kawachi. Michael Botticelli of the Grayken Center for Addiction at Boston Medical Center was also a co-author.

Funding for the study came from Templeton Foundation grants 52125 and 61075, and from National Institutes of Health grant CA222147. The Nurses’ Health Study II is supported by grants U01 CA176726 and R01 CA67262 from the NIH, and the Health Professionals Follow-Up Study is supported by grants UM1 CA167552 and R01 HL35464 from the NIH.

This is part of our Coronavirus Update series in which Harvard specialists in epidemiology, infectious disease, economics, politics, and other disciplines offer insights into what the latest developments in the COVID-19 outbreak may bring.

Since the early days of the COVID-19 crisis, scientific literature and news reports have dedicated much attention to two groups of patients — those who develop critical disease and require intensive care and those who have silent or minimally symptomatic infections.

Such accounts have mostly overlooked another large and important category of patients — those with symptoms concerning enough to seek care, yet not serious enough to need hospital treatment.

Now, a new report by researchers at Harvard Medical School and Harvard-affiliated Cambridge Health Alliance offers insights into this in-between category based on data collected from people presenting at an outpatient COVID-19 clinic in Greater Boston.

The team’s observations, published April 20 in the journal Mayo Clinic Proceedings, are based on data from more than 1,000 patients who have sought care for respiratory illness since COVID-19 was declared a pandemic in March.

The findings offer a compilation of clues that can help clinicians distinguish between patients with COVID-19 infections and those with other conditions that may mimic COVID-19 symptoms.

Such clues are critical because early triage and rapid decision-making remain essential even now that testing is becoming more widely available than it was in the early days of the pandemic, the research team said. Testing remains far from universal, and even when available, tests still may have a turnaround time of one to three days. Additionally, some rapid point-of-care tests that have emerged on the market have not been entirely reliable and have caused false-negative readings.

“Early recognition and proper triage are especially important given that in the first days of infection, people infected with SARS-CoV-2 may experience symptoms indistinguishable from a variety of other acute viral and bacterial infections,” said study lead author Pieter Cohen, an associate professor of medicine at Harvard Medical School (HMS) and a physician at Cambridge Health Alliance. “Even when point-of-care diagnostic tests are available, given the potential for false-negative results, understanding the early natural history of COVID-19 and good old-fashioned clinical skills will remain indispensable for proper care.”

A nuanced understanding of the typical presentation of COVID-19 in the outpatient setting can also help clinicians determine how often to check back with patients, the researchers added. For example, those who have started developing shortness of breath demand very close monitoring and frequent follow-up to check how the shortness of breath is evolving and whether a patient may be deteriorating and may need to go to the hospital.

According to the report, COVID-19 typically presents with symptoms suggestive of viral infection, often with low-grade fever, cough and fatigue, and, less commonly, with gastrointestinal trouble. Shortness of breath usually emerges a few days after initial symptoms, becomes most pronounced upon exertion and may involve sharp drops in blood oxygen levels.

Chief among the team’s findings

• Fever is not a reliable indicator. If present, it could manifest only with mild elevations in temperature.
• COVID-19 may begin with various permutations of cough without fever, sore throat, diarrhea, abdominal pain, headache, body aches, back pain and fatigue
• It can also present with severe body aches and exhaustion.
• A reliable early hint is loss of the sense of smell in the first days of disease onset.
• In serious COVID-19, shortness of breath is a critical differentiator from other common illnesses.
• Almost no one, however, develops shortness of breath, a cardinal sign of the illness, in the first day or two of disease onset.
• Shortness of breath can appear four or more days after onset of other symptoms.
• The first days after shortness of breath begins are a critical period that requires close and frequent monitoring of patients by telemedicine visits or in-person exams.
• The most critical variable to monitor is how the shortness of breath changes over time. Oxygen saturation levels can also be a valuable clue. Blood oxygen levels can drop precipitously with exertion, even in previously healthy people.
• A small number of people may never develop shortness of breath but may have other symptoms that could signal low oxygen levels, including dizziness or falling.
• Anxiet — common among worried patients with viral symptoms suggestive of COVID-19 — can also induce shortness of breath.

Distinguishing between anxiety-induced shortness of breath and COVID-19-related shortness of breath is critical. There are several ways to tell the two apart.

Key differentiators

• Time of onset: Anxiety-induced shortness of breath occurs rapidly, seemingly out of the blue, while COVID-19 shortness of breath tends to develop gradually over a few days.
• Patient description of sensation: Patients whose shortness of breath is caused by anxiety often describe the sensation occurring during rest or while trying to fall asleep but does not become more pronounced with daily activities. They often describe a sensation of inability to get enough air into their lungs. By contrast, shortness of breath induced by COVID-19-related drops in oxygen gets worse with physical exertion, including performing simple daily activities like walking, climbing stairs or cleaning.
• Anxiety-related shortness of breath does not cause drops in blood oxygen levels

During a clinical exam, a commonly used device, the pulse oximeter, can be valuable in distinguishing between the two. Clipped onto one’s finger, the device measures blood oxygen levels and heart rate in a matter of seconds.

Several types of pneumonia — a general term denoting infection in the lungs — can present with striking similarity to COVID-19. For example, COVID-19 respiratory symptoms appear to closely mimic symptoms caused by a condition known as pneumocystis pneumonia, a pulmonary infection predominantly affecting the alveoli, the tiny air sacs lining the surface of the lungs. Both COVID-19 patients and patients with pneumocystis pneumonia experience precipitous drops in oxygen levels with exertion and shortness of breath. However, in the case of pneumocystis pneumonia, the shortness of breath typically develops insidiously over weeks, not within days, as is the case with COVID-19. Here, a careful patient history detailing evolution of symptoms would be critical, the authors said.

Likewise, during the initial days of infection, both the flu and COVID-19 may have identical presentations, but thereafter the course of the two infections diverges. People with uncomplicated flu rarely develop significant shortness of breath. When they do experience trouble breathing, the shortness of breath is mild and remains stable. On the rare occasion of when flu causes a viral pneumonia, patients deteriorate rapidly, within the first two to three days. By contrast, patients with COVID-19 don’t begin to develop shortness of breath until several days after they first become ill.

Study co-investigators include Lara Hall, Janice Johns and Alison Rapaport.

Relevant disclosures: Cohen has received compensation from UpToDate, a company providing clinical decision-support tools.

Brian Strickland was high up in the Himalayas, walking around a rustic clinic a day’s hike from Mount Everest. He was trying to find a cellphone signal strong enough to get email and news from home as the coronavirus outbreak was evolving from being viewed as a crisis largely focused in central China to a global pandemic centered on the U.S.

Strickland would be on a helicopter to Kathmandu within days, the first leg of his trip back to Massachusetts, where he’d witness the rapid escalation of the COVID-19 epidemic from the intimate point of view of an emergency room physician. Within weeks, he’d be heading a Massachusetts General Hospital (MGH) clinical trial exploring the use of inhaled nitric oxide — a therapy built on knowledge gained high in Himalayas — to rapidly kill coronavirus in the lungs.

“Yesterday was my first full day off in a stretch of 10 days of shifts since I got back,” Strickland said in early April. “It shows how quickly pandemics can completely change our lives.”

The turnaround was breathtaking for Strickland, who is in the first year of a two-year fellowship in wilderness medicine. The unique program, one of the nation’s oldest, is headquartered at MGH and has a dual focus that seems made for the current crisis: training physicians to deliver medical care in extreme and low-resource settings, and fostering research around problems of low oxygen at high altitude.

Founder N. Stuart Harris, a Harvard Medical School associate professor of emergency medicine and chief of MGH’s Division of Wilderness Medicine, has long studied the effects of altitude sickness and how to treat it in Everest climbers, whose final sprint to the 29,000-foot summit occurs in what climbers call the “death zone,” where air pressure and oxygen levels are too low for normal lung function.

That work, Harris said, has led to the current clinical trial, leveraging insights from research done at high altitude to design a treatment that, should it work, would kill coronavirus directly in the lungs and allow patients to be discharged from the emergency department to home. The key insight, he said, is that the lack of oxygen at high altitude mirrors the effects of COVID-19’s lung dysfunction on the cell’s mitochondria powerhouse. It is also well-known that nitric oxide, which improves blood flow in the lungs, is central to adapting to life at high altitudes and has antiviral benefits.

“If successful, this relatively simple therapy will give us the ability to treat and safely discharge patients from the ED to home, thereby reducing demand for the extremely limited supply of ICU beds,” Harris wrote in a recent letter to the division’s supporters. “This exciting work plays to our strengths of working in concert with the best minds on the planet to seek elegant and innovative low-tech solutions for complex problems.”

What makes a wilderness fellow?

Not every wilderness medicine fellow focuses on the hazards of the Earth’s high places. Some devote their attention to the challenge of hyperbaric medicine, which treats scuba diving injuries, others to climate change, or life above the Arctic Circle. Harris said what’s common among them — other than a love of the outdoors — is that they see human health as an ecological phenomenon that depends on a functioning biosphere and believe that expert medical care should be available wherever it’s required.

“Health care isn’t an architectural phenomenon,” Harris said. “It is about people. Wilderness medicine teaches doctors to provide compassionate, resource-limited medical care under austere conditions. A hospital is a box. We think outside the box.”

This is part of our Coronavirus Update series in which Harvard specialists in epidemiology, infectious disease, economics, politics, and other disciplines offer insights into what the latest developments in the COVID-19 outbreak may bring.

One of the most popular — and highest-stakes — guessing games to emerge from the coronavirus pandemic is how long it will take to get a vaccine. A Harvard infectious disease expert said on Thursday that how far we are from a vaccine will likely depend on who’s asking.

“The question is: ‘Who is ‘we?’” said Barry Bloom, the Joan L. and Julius H. Jacobson Research Professor of Public Health and former dean of the Harvard T.H. Chan School of Public Health. If “we” are healthy volunteers willing to be inoculated to see whether an experimental vaccine works, the answer is that some are already getting it, and more will be enrolled in the coming months. Once an effective solution emerges, hopefully by early next year, it may take another six to eight months to reach priority populations like U.S. health care workers and first responders. Other essential workers, including those toiling for low wages in grocery stores and food production, should not be forgotten, Bloom said.

For still others, particularly those in developing nations, the answer is considerably different.

“If ‘we’ is a person in Burkina Faso, or Laos, and [they are] expecting to see a vaccine in the next three years, I would be very surprised [if they see it],” said Bloom, who spoke during a Facebook Live event sponsored by The Forum at Harvard T.H. Chan School of Public Health and PRI’s “The World.”

Complicating the already-tense global COVID picture, Bloom said, has been an increase in nationalism in the U.S. and elsewhere, which is at odds with equitable distribution of scientific gains against the SARS-CoV-2 virus and global health goals. The Trump administration, for instance, skipped a meeting of global leaders late last month called to get them to commit to distribute any future vaccine in an equitable way and declined this week to attend a fundraising conference by the European Union to coordinate vaccine efforts. The head of one of the world’s largest vaccine processing operations in India said in a recent media report that any vaccine it produces will go to protect India’s population before doses are sent abroad.

Further, increased tension between the U.S. and China over the virus’ origins threatens the free flow of scientific information, marked early on by Chinese researchers sharing the viral genome in the pandemic’s opening weeks. That spirit of cooperation has been key to the rapid international scientific response to the outbreak, one that has nonetheless been outpaced by the virus’ spread. Scientists have been sharing information about the virus and the illness it causes nearly as quickly as the data has become available, Bloom said, flooding the traditional scientific journals with new information and prompting the publication of unreviewed work on preprint servers and even in scientists’ Twitter posts.

“I’ve not seen anything like this in my entire career,” Bloom said. “This is moving at lightning speed. Not everything you read is going to turn out to be correct, but at least the information is being shared.”

Development of treatments is moving on a parallel track, Bloom said, and the recent findings that the drug remdesivir is effective in lessening illness severity is promising. Bloom pointed out that optimism has to be tempered by the fact that several of those given the drug died and that the virus could still be found in the bodies of those treated. Still, he said, most of those tested were seriously ill, and some believe that giving the drug to patients earlier in the course of their illness may make an even more significant impact. Public health officials have underscored that remdesivir is a treatment, not a cure, and it’s possible that its greatest importance may be as a proof of concept that will lead to better therapies.

Until effective treatments or vaccines are widely available, the predominant tools for government leaders will remain social distancing, personal protective equipment, and other measures already in use. Yonatan Grad, the Melvin J. and Geraldine L. Glimcher Assistant Professor of Immunology and Infectious Diseases, said Thursday that as more localities and states begin to relax social-distancing requirements, it’s important we begin to think about what to do when infections resurge, as is expected.

Grad said very little thought is being given to what the reimposition of controls will look like, even though they may not necessarily mirror current practices. That’s because, he said, a lot has been learned about what works and what doesn’t. He said it’s likely that controls could be more targeted and less the “blunt instrument” that widespread social distancing has been during the initial response.

“Can we use more refined measures? Can we combine social distancing of varying kinds with contact tracing, as well as quarantine and isolation?” Grad asked. “Trying to balance the types of interventions we have available to us with the context in which we’re seeing a resurgence is going to be critical. … I think that’s an extremely important question, and one that I have not seen well addressed.”

Grad, who spoke to the media during a morning conference call, also called into question the idea of issuing immunity “passports” to people who have already been sick or who test positive using antibody tests. Aside from the potential for inequitable use of the passports, Grad said the available tests, many of which were allowed on the market without review, are prone to false positives, particularly in places where there have been relatively few COVID cases. What that means, he said, is that people who think they’re immune and are back at work and out in the community may be susceptible to getting the virus. Instead of contributing to herd immunity, they may contribute to the virus’ spread.

Inaccurate tests could also further muddy our understanding of whether infection confers immunity at all, since someone with a false-positive result who subsequently gets sick may reasonably wonder whether getting the illness provides any protection at all.

“You could be in a situation where … you’re actually introducing into the population people who you think are positive, but enough of them are actually negative that you could be below the herd-immunity threshold,” Grad said.

This is part of our Coronavirus Update series in which Harvard specialists in epidemiology, infectious disease, economics, politics, and other disciplines offer insights into what the latest developments in the COVID-19 outbreak may bring.

When a disease outbreak grabs the public’s attention, formal recommendations from medical experts are often muffled by a barrage of half-baked advice, sketchy remedies, and misguided theories that circulate as anxious people rush to understand a new health risk.

The current crisis is no exception. The sudden onset of a new, highly contagious coronavirus has unleashed what U.N. Secretary-General António Guterres last week called a “pandemic of misinformation,” a phenomenon that has not gone unnoticed as nearly two-thirds of Americans said they have seen news and information about the disease that seemed completely made up, according to a recent Pew Research Center study.

What distinguishes the proliferation of bad information surrounding the current crisis, though, is social media. Kasisomayajula “Vish” Viswanath, Lee Kum Kee Professor of Health Communication at the Harvard T.H. Chan School of Public Health, said the popularity and ubiquity of the various platforms means the public is no longer merely passively consuming inaccuracies and falsehoods. It’s disseminating and even creating them, which is a “very different” dynamic than what took place during prior pandemics MERS and H1N1.

The sheer volume of COVID-19 misinformation and disinformation online is “crowding out” the accurate public health guidance, “making our work a bit more difficult,” he said.

“Misinformation could be an honest mistake or the intentions are not to blatantly mislead people,” like advising others to eat garlic or gargle with salt water as protection against COVID-19, he said. Disinformation campaigns, usually propagated for political gain by state actors, party operatives, or activists, deliberately spread falsehoods or create fake content, like a video purporting to show the Chinese government executing residents in Wuhan with COVID-19 or “Plandemic,” a film claiming the pandemic is a ruse to coerce mass vaccinations, which most major social media platforms recently banned.

In order to be effective, especially during a crisis, public health communicators have to be seen as credible, transparent, and trustworthy. And there, officials are falling short, said Viswanath.

“People are hungry for information, hungry for certitude, and when there is a lack of consensus-oriented information and when everything is being contested in public, that creates confusion among people,” he said.

“When the president says disinfectants … or anti-malaria drugs are one way to treat COVID-19, and other people say, ‘No, that’s not the case,’ the public is hard-pressed to start wondering, ‘If the authorities cannot agree, cannot make up their minds, why should I trust anybody?’”

Mainstream media coverage has added to the problem, analysts say. At many major news outlets, reporters and editors with no medical or public health training were reassigned to cover the unfolding pandemic and are scrambling to get up to speed with complex scientific terminology, methodologies, and research, and then identify, as well as vet, a roster of credible sources. Because many are not yet knowledgeable enough to report critically and authoritatively on the science, they can sometimes lean too heavily on traditional journalism values like balance, novelty, and conflict. In doing so, they lift up outlier and inaccurate counterarguments and hypotheses, unnecessarily muddying the water.

“That’s a huge challenge,” said Ashish Jha, K.T. Li Professor of Global Health and Director of the Harvard Global Health Institute, during an April 24 talk about COVID-19 misinformation hosted by the Technology and Social Change Research Project at the Shorenstein Center for Media, Politics and Public Policy.

“What I have found is a remarkable degree of consensus among people who understand the science of this disease around what the fundamental issues are and then disagreements about trade-offs and policies,” said Jha, who is a frequent commentator on news programs. “The idea of covering the science in a two-sided way on areas where there really isn’t any disagreement has struck me as very, very odd, and it keeps coming up over and over again.”

Then there is the problem of political bias. This has been especially true at right-leaning media outlets, which have largely repeated news angles and viewpoints promoted by the White House and the president on the progress of the pandemic and the efficacy of the administration’s response, boosting unproven COVID-19 treatments and exaggerating the availability of testing and safety equipment and prospects for speedy vaccine development.

Tara Setmayer, a spring 2020 Resident Fellow at the Institute of Politics and former Republican Party communications director, said what’s coming from Fox News and other pro-Trump media goes well beyond misinformation. Whether downplaying the views of government experts on COVID-19’s lethality, blaming China or philanthropist Bill Gates for its spread, or cheering shutdown protests funded by Republican political groups, it’s all part of “an active disinformation campaign,” she said, aimed at deflecting the president’s responsibility as he wages a reelection campaign.

COVID-19 has changed the way we live. For a few, like Annie Cheng, it’s also practically changed where they live.

“I have a completely different lifestyle now,” she said. “Pretty much the lab is my home.”

Cheng, the lead technologist at Beth Israel Deaconess Medical Center’s molecular diagnostics lab, is among those toiling to transform it from a regular 7 a.m.‒5 p.m., five-day-a-week operation into one of New England’s foremost hospital-based testing centers for SARS-CoV-2, the virus that causes COVID-19.

The lab has super-charged its capacity. It recently performed 1,000 tests in a day and can do as many as 1,500, an entire season’s worth of flu diagnostics. This has meant longer hours for everyone, new testing machines, and redesigned procedures to keep workers safe. But the real game-changer has been the influx of skilled volunteers from Beth Israel’s research labs, which were closed after social-distancing edicts went into effect.

“Ordinarily, we have a small number of people in our clinical lab who do this [testing] work,” said Jeffrey Saffitz, chair of Beth Israel’s Pathology Department and Mallinckrodt Professor of Pathology at Harvard Medical School (HMS). “All of the basic science laboratories at Harvard Medical School and its hospitals have been closed down, so we have this large population of research techs and postdocs who run PCR machines all the time in a research setting. We put out a call and we were gratified to have a great response. It’s a story where our community of smart, incredibly committed people will do whatever it takes to stem this terrible tragedy.”

The scramble began in mid-March, when the government allowed hospital labs to begin their own testing for SARS-CoV-2 instead of sending samples to centralized government facilities for results. The change came as U.S. disease numbers skyrocketed and what had been insistent calls for increased testing capacity rose to a shout.

Beth Israel has two main labs that do its clinical testing. Officials decided that one, the molecular diagnostics lab, equipped with high-volume machines, would handle the COVID tests. The lab, however, was initially hamstrung by a lack of test kits that would allow its machines to check samples for COVID. The shortage was met by Aldatu Biosciences, a startup with roots in Harvard’s i-lab and Pagliuca Life Lab. Soon afterward, supplies from Abbott Laboratories, which makes the machines, began to flow.

The stories of how the COVID-19 pandemic has upended work and life are as diverse as the new challenges and pressures the disease has created. The Gazette asked alumni who are engaged in the battle against the disease to share their experiences and how their work has radically changed.

NGOZI EZIKE ’94

Chicago
Director of the Illinois State Department of Public Health

This is part of our Coronavirus Update series in which Harvard specialists in epidemiology, infectious disease, economics, politics, and other disciplines offer insights into what the latest developments in the COVID-19 outbreak may bring.

Much of Deirdre Barrett’s work has involved the study of dreams, particularly the distressing dreams and nightmares of those affected by trauma, including combat veterans, former prisoners of war, and 9/11 first responders. More recently, the assistant professor of psychology in the Department of Psychiatry at Harvard Medical School, whose books include “The Committee of Sleep” and “Trauma and Dreams,” has created an online survey to collect the dreams of people living through the coronavirus pandemic. To date she has more than 2,500 responses recounting more than 6,000 dreams. Barrett spoke with the Gazette about how she sees the outbreak affecting the quality and content of people’s dreams.

Q&A

Deirdre Barrett

GAZETTE: What exactly is happening in our subconscious during periods of extreme stress? How is that manifesting in our dreams?

BARRETT: When we dream, our brain is in this state where visual areas are much more active than when we’re awake, and on average, emotional areas are a little more active. Our prefrontal cortex right behind our forehead, which controls the most precise linear logic and also censors inappropriate social things, as well as the right way to do things in our professional thinking, is very much damped down. Our verbal areas are somewhat less active. So, I think we’re thinking about the same things that we were most focused on by day, but in this other state of consciousness. We have more intuitive thinking and less linear thinking about things. Once in a while, we’ll see that our unconscious looks much more scared than we’re feeling by day or provides us with some optimistic perspective that we haven’t had by day. But I think in general, being anxious by day and having anxiety dreams correlate both as traits that a person carries over long periods of time, but also as a state for a short period of time when there’s a stressor.

GAZETTE: Do you think extra sleep, or lack of sleep, might contribute to vivid coronavirus dreams?

BARRETT: More sleep than usual, such as many people are getting now, means more dream time. And it’s not just proportional: Our last REM period of the night is the longest and more “dense” in REM, which correlates with long, vivid dreams, so an alarm clock chopping off a bit of sleep chops off a lot of dreaming. The relationship to insomnia is more complicated. If one is simply sleeping a shorter time, then there’s less dreaming. However, if less sleep is because of frequent awakenings — whether due to noise, anxiety, etc. — one is likely to awaken out of more REM periods, which results in more dream recall though not more actual dreaming.