With the delta variant wreaking havoc on unvaccinated populations, the ability to quickly diagnose and track emerging variants of the virus is crucial. Researchers have now created a simple, inexpensive, CRISPR-based diagnostic test that allows users to test themselves for multiple variants of the SARS-CoV-2 virus at home, using just a sample of their saliva.

Developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Massachusetts Institute of Technology, and several Boston-area hospitals, the diagnostic device, called Minimally Instrumented SHERLOCK (miSHERLOCK), is easy to use and provides results that can be read and verified by an accompanying smartphone app within one hour.

miSHERLOCK successfully distinguished between three different variants of SARS-CoV-2 in experiments, and can be rapidly reconfigured to detect additional variants like delta. The device can be assembled using a 3D printer and commonly available components for about $15, and re-using the hardware brings the cost of individual assays down to $6 each.

“miSHERLOCK eliminates the need to transport patient samples to a centralized testing location and greatly simplifies the sample preparation steps, giving patients and doctors a faster, more accurate picture of individual and community health, which is critical during an evolving pandemic,” said co-first author Helena de Puig, a postdoctoral fellow at the Wyss Institute and MIT.

The diagnostic device is described in a paper published Friday in Science Advances.

From supply chain to SHERLOCK

As an instructor in pediatrics at Boston Children’s Hospital with a specialization in infectious diseases, co-first author Rose Lee has been working on the front lines of the COVID-19 pandemic for over a year. Her experiences in the clinic provided inspiration for the project that would ultimately become miSHERLOCK.

A new study by researchers at Harvard-affiliated Massachusetts General Hospital has found that crowding in prisons dramatically increases COVID risk among inmates. And the authors of the study, published in JAMA Internal Medicine, argue that policy changes are necessary to protect incarcerated men and women.

Previous studies had found that coronavirus infection was significantly higher in prisons than in the general population, but the degree to which crowding contributes to the problem had been unknown. In the recent study, senior author Amir Mohareb, an infectious disease doctor, and his colleagues analyzed a trove of data from Massachusetts state prisons. The data included weekly reports on the number of positive tests at 14 facilities, the population of each prison, and the number of inmates each facility was designed to hold, or design capacity.

As prisons became more crowded, the threat to inmates rose. Every increase of 10 percentage points in population relative to the facility’s design capacity raised the risk of COVID infection by 14 percent. The upshot, as the researchers note, is that a facility doesn’t have to exceed its design capacity to increase the danger for inmates, since a prison that’s operating at 80 percent capacity is riskier than one at 70 percent capacity.

“We may need to have stricter thresholds for where we draw the line on how crowded a facility can be,” said Mohareb, an instructor at Harvard Medical School and a researcher at MGH’s Medical Practice Evaluation Center. Mohareb has worked on a pro bono basis with advocacy groups seeking to ensure that infection control measures are implemented in prisons during the pandemic. One group he advised, Prisoners’ Legal Services of Massachusetts, has sued the state Department of Correction over its practices.

To study the effect of crowding another way, Mohareb’s team calculated the percentage of inmates in each prison who were housed in single cells during each week of the observation period. They found that every 10 percentage point increase in the proportion of inmates living in single cells reduced the risk of COVID infection in that prison by 18 percent.

Similar to other studies, this investigation found that prison inmates have a significantly greater risk — more than sixfold — than the general public for becoming infected with COVID. But in a novel finding, Mohareb and colleagues showed that infection rates in prisons tended to reflect those of their surrounding communities. When COVID cases dropped in the summer of 2020, the change showed up in prisons. And as numbers spiked in many communities late last year, they soared in local prisons. “Prisons are intricately linked to their surrounding communities,” says Mohareb. He urged greater attention to testing and vaccination among guards, support staff, and vendors.

While COVID vaccination became available to inmates in Massachusetts state prisons earlier this year, it is optional; what’s more, news reports indicate that a significant portion of prison workers remain unvaccinated. Mohareb and his coauthors argue that policymakers should strongly consider decarceration — releasing prisoners deemed to be at low risk for reoffending — as a way to lower the risk for COVID-19 in prisons.

“It was the almost universal opinion of experts in public health, infectious disease, and epidemiology from the start of the pandemic that prisons were going to be places of immense suffering unless inmates were released in a coordinated manner,” said Mohareb. “And that really didn’t happen.”

First author Abigail I. Leibowitz worked on the study while earning a master’s degree in public health at the Harvard T.H. Chan School of Public Health and is currently a medical student at the University of Colorado. Other authors include infectious disease physician Mark Siedner and psychiatrist Alexander C. Tsai, both of MGH.

Support for the research was provided by the National Institutes of Health and the Sullivan Family Foundation.

Genetic mutations that promote the growth of the most common type of adult brain tumors can be accurately detected and monitored in blood samples using an enhanced form of liquid biopsy developed by researchers at Harvard-affiliated Massachusetts General Hospital (MGH).

Comparing blood samples from patients with gliomas with tumor biopsy tissues from the same patients, Leonora Balaj, Bob S. Carter, and other MGH investigators in the Department of Neurosurgery found that a novel digital droplet polymerase chain reaction (ddPCR) blood test they pioneered could accurately detect and monitor over time two mutations of the gene TERT. The mutations, labeled C228T and C250T, are known to promote cancer growth and are present in more than 60 percent of all gliomas, and in 80 percent of all high-grade gliomas, the most aggressive and life-threatening type.

Their discovery, which has the potential to substantially improve the diagnosis and monitoring of gliomas, is reported in the journal Clinical Cancer Research.

Gliomas are tumors of glia, central and peripheral nervous system cells that support and protect neurons, the cells that transmit electrical impulses.

Liquid biopsy is a method for detecting cancer by looking for fragments of tumor DNA that circulate in blood. The technique has been shown to be sensitive at detecting the presence of some forms of cancer, but brain tumors have until now posed a formidable barrier.

“Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at much lower level than any other types of tumors,” Balaj says.

“By ‘supercharging’ our ddPCR assay with novel technical improvements, we showed for the first time that the most prevalent mutation in malignant gliomas can be detected in blood, opening a new landscape for detection and monitoring of the tumors,” she says.

The researchers first tested the performance of the ddPCR assay in tumor tissue and found that the results were in perfect agreement with the results from an independently performed clinical laboratory assessment of TERT mutations in the tumor specimens.

They then looked at samples of blood plasma matched to patient tumors and found that the ddPCR assay could detect TERT mutations both in samples from MGH as well as from similarly matched plasma and tumor samples from collaborators at other institutions.

The ddPCR assay has an overall sensitivity (ability to detect the presence of a glioma) of 62.5 percent, which is a tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors, compared to the standard of tissue-based detection of TERT mutations.

The test is easy to use, quick, and low cost, and could be performed in most laboratories, Balaj says. Importantly, the test can also be used to follow the course of disease. “We envision the future integration of tests like this one into the clinical care of our patients with brain tumors,” says Carter, chief of Neurosurgery and co-director of the MGH Brain Tumor Center. “For example, if a patient has a suspected mass on MRI scanning, we can take a blood sample before the surgery and assess the presence of the tumor signature in the blood, and then use this signature as a baseline to monitor as the patient later receives treatment, both to gauge response to the treatment and gain early insight into any potential recurrence.”

The team’s goal is to expand this blood test to be able to differentiate many types of brain tumors.

An experimental medication that was recently shown to slow the progression of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) has now demonstrated the potential to also prolong patient survival. The findings come from a clinical trial conducted by investigators at the Sean M. Healey & AMG Center for ALS at Harvard-afilliated Massachusetts General Hospital (MGH) and Amylyx Pharmaceuticals, Inc., the company that manufactures the medication.

Amylyx developed AMX0035, the investigational neuroprotective therapy evaluated in the CENTAUR trial and designed to reduce the death and dysfunction of motor neurons.

ALS, a degenerative condition without a cure, attacks brain and spinal cord nerve cells to progressively affect individuals’ ability to move, speak, eat and even breathe. The new results, reported in the journal Muscle and Nerve, provide additional proof of the benefits that patients with ALS may experience when taking the oral drug called AMX0035, which is a combination of sodium phenylbutyrate and taurursodiol. These components target oxidative stress within nerve cells’ energy-producing mitochondria and protein-processing endoplasmic reticulum to help prevent neurodegeneration.

In the CENTAUR trial, 137 participants with ALS were randomized two-to-one to receive AMX0035 or placebo. Recently, investigators demonstrated that AMX0035 slowed ALS disease progression over six months, with impacts on various activities of daily living such as a patient’s ability to walk, talk, use utensils or swallow food. Patients who completed CENTAUR were eligible to participate in an open-label extension (in which all patients received AMX0035) aimed at assessing the long-term safety and efficacy of the medication.

Investigators’ nearly three-year survival analysis incorporated all participants who enrolled in CENTAUR, whether they continued long-term treatment with AMX0035 in the open-label extension or not. The team found that participants originally randomized to receive AMX0035 lived for a median of 6.5 months longer than those originally randomized to receive the placebo.

“These findings are an important step forward because, in this trial, early treatment with AMX0035 was associated with longer survival in people with ALS,” said the study’s leader Sabrina Paganoni, investigator at the Healey & AMG Center for ALS and assistant professor of physical medicine and rehabilitation at Harvard Medical School and Spaulding Rehabilitation Hospital. “These results provide substantial evidence supporting the role of AMX0035 for the treatment of ALS. Next steps will depend on ongoing discussions with regulatory agencies.”

Senior author Merit Cudkowicz, director of the Healey & AMG Center for ALS at MGH, chief of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at Harvard Medical School, added, “This is one of the first studies to show effect on both function and survival. We are hopeful that this is just the beginning of many new treatments for ALS.”

The trial was a collaboration among the Healey & AMG Center, Amylyx Pharmaceuticals, Inc., the ALS Association, ALS Finding a Cure, and academic partners such as the Northeast ALS Consortium (NEALS), the MGH Biostatistics Center, and the Barrow Neurological Institute.

A team led by Harvard researchers found that presentations about COVID-19 delivered by physicians improved knowledge about the disease and preventive behaviors across racial lines. But their study also discovered that messages tailored to Black audiences and presented by physicians of color did not enhance the effectiveness for minority participants.

“One of the things that we found that was very reaffirming, despite different races and ethnic minority backgrounds, despite different sort[s] of economic and political affiliations, we saw that when health care providers deliver very clear and accurate health-leading information, it can have a positive impact across all these demographics,” said lead author Lucy Ogbu-Nwobodo, a resident physician at Massachusetts General Hospital and at McLean Hospital.

Emily Breza, an associate professor in the Department of Economics and Ogbu-Nwobodo’s co-author, noted the findings confirmed that physicians, regardless of their race, have a “trusted messenger” status. That status allows the information they deliver to “cut across these different political and racial community markers and … lead to behavior change.”

The study, “Effect of Physician-Delivered COVID-19 Public Health Messages and Messages Acknowledging Racial Inequity on Black and White Adults’ Knowledge, Beliefs, and Practices Related to COVID-19,” was published in JAMA Network Open on July 14, and marks a follow-up to research published in the Annals of Internal Medicine in April.

The researchers were particularly interested to know whether targeted messaging — including American Medical Association acknowledgment of racial injustice as a public health threat — made a difference. Throughout the pandemic, people of color have been at much greater risk of infection, hospitalization, and death from COVID than white Americans.

The trial confirmed earlier research showing how greatly Americans value information passed on by trusted medical professionals, Breza said. Previous work showed that a non-physician, public intellectual, such as a Nobel Prize winner in economics, could also change behavior.

“I think across the board, a few very simple messages delivered by these trusted medical professionals have, surprisingly, moved the needle and done it pretty consistently across the board across different demographic groups,” she said.

While the specially crafted presentations failed to increase the effectiveness of disease education, they did make both Black and white participants more willing to donate to COVID-19 charities in general and to pandemic relief nonprofits geared toward the Black community in particular.

Subjects in the 2020 randomized clinical trial of 18,223 Black and white adults were shown a series of health messages delivered by Black and white physicians about COVID-19 and preventive behaviors. Participants were also shown one of two statements from the AMA, one on structural racism and another on drug price transparency.

Highlighting health issues that disproportionally affect communities of color is one step toward increasing public awareness of structural racism in health care, the study found. Ogbu-Nwobodo said that it is important for the health care community to acknowledge and address existing racial inequities.

“We know that people of color experience our health care [system] very differently. … [T]hey’re treated differently based on their skin color,” she said. “So, what are we doing as a health care system independent of just COVID to ensure that these issues are no longer being passed over with flowery statements of support?”

Members of the health care community should take “an honest inventory” of the ways they are perpetuating the issue as providers and at an organizational level, Ogbu-Nwobodo said.

Findings were published by members of the COVID-19 Working Group, a coalition of researchers and physicians from Harvard’s Faculty of Arts and Sciences, Harvard Medical School, Harvard Kennedy School of Government, Massachusetts General Hospital, and McLean Hospital, as well as MIT, Yale, Stanford University, Ludwig Maximilian University of Munich, and the Paris School of Economics.

The COVID-19 Working Group plans to continue its work by looking into scaled-up messaging by doctors using social media.

This work was partially funded by the National Science Foundation and National Institutes of Health.

Risk factors for heart health, such as smoking, unhealthy diets and minimal physical activity, may seem personal, but for people who are married or in a domestic partnership, the behavior patterns of one person may be strongly linked to the patterns of the other.

A new study led by investigators from Harvard-affiliated Brigham and Women’s Hospital assessed cardiovascular risk factors and behaviors of more than 5,000 couples who took part in an employee wellness program offered by Quest Diagnostics. The team used several metrics to classify people as having ideal or non-ideal risk factors and behaviors, finding that in 79 percent of couples, both people fell into the non-ideal category for cardiovascular health, with most sharing unhealthy diets and getting inadequate exercise. The findings point out the potential importance of addressing healthy behaviors for both people in a relationship. Results are published in JAMA Network Open.

“We know a lot about cardiovascular risk factors for individuals but not for couples,” said corresponding author Samia Mora of the Brigham Divisions of Preventive Medicine and Cardiovascular Medicine. “We expected to see some shared risk factors, but it was a surprise to see that the vast majority of couples were in a non-ideal category for overall cardiovascular health.”

Mora and colleagues examined data from Quest Diagnostics, which offered a voluntary health assessment program to its employees. Researchers analyzed data from 5,364 couples (10,728 individuals) who joined the program between October 2014 and August 2015. The researchers determined whether each individual was in the ideal, intermediate, or poor category for each of the American Heart Association-defined Life’s Simple 7 (LS7) risk factors and behaviors. The LS7 include smoking status, body mass index, physical activity, healthy diet score, total cholesterol, blood pressure and fasting glucose. The team also gave each participant an overall cardiovascular (CV) health score. Data were collected from questionnaires, examinations and laboratory tests.

When examined individually, more than half of the participants were in the ideal category for three LS7 risk factors and behaviors: smoking status (never smoked), total cholesterol (<200 mg/dL), and fasting glucose (<100 mg/dL, Table 2). But more than a quarter of the individuals were in the poor categories for BMI, physical activity, and CV health score. Only 12 percent of individuals were in the ideal category for CV health score.

When both people in the couple were considered together, more than half of couples shared all LS7 risk factors and behaviors as well as CV health score. When one member of a couple was in the ideal category, the second member was more likely to be in the ideal category for all factors except for total cholesterol. But 79 percent of couples were both in the non-ideal category for CV health score, largely driven by unhealthy diet and inadequate exercise.

The team did find that when one partner had quit smoking, lost weight, increased their physical activity or improved their diet, the other partner was more likely to have done so. But over the five-year study period, the health of couples, risk factors and behavior patterns remained relatively unchanged overall. Apart from modest changes in blood pressure and fasting glucose, the team found no significant changes in factors.

The authors note that some of the data in the study comes from self-reporting, which can be inaccurate, and that the longest duration for follow up was five years. The study only examined data for employees who chose to participate in the company’s wellness program, but it was a diverse population. The team found some variation by ethnicity, socioeconomic status, and geographic location.

“Our data suggest that risk factors and behaviors track together for couples,” said Mora, who is an associate professor of medicine at Harvard Medical School. “Rather than thinking about interventions for individuals, it may be helpful to think about interventions for couples or whole families. And it’s important for people to think about how their health and behaviors may influence the health of the person(s) they are living with. Improving our own health may help others.”

Mora has served as a consultant for Quest Diagnostics for work outside the current study. Four co-authors are employees of Quest Diagnostics.

Since the pandemic began, parents and researchers have been trying to understand how it affects children’s mental health. For 18 months, children have dealt with the disruption of their daily lives, fear of COVID-19 contagion, and sometimes death in the family. The emergence and spread of the coronavirus delta variant has renewed the uncertainty about young people’s safety as schools have started to reopen across the country.

In a new paper published in PLOS ONE researchers from Harvard’s psychology department — research associate Maya L. Rosen, postdoctoral fellow Alexandra M. Rodman, Ph.D. ’18, doctoral candidate Steven W. Kasparek, and clinical psychologist Katie L. McLaughlin, professor of psychology — worked with colleagues from the University of Washington to examine the impact of pandemic stressors on children’s mental health. A goal was to develop a set of practical strategies for caregivers to help young people develop more resilience to potential mental health problems.

“The biggest thing that we hope parents take from the study is that while youth mental health has been negatively impacted by the pandemic, there are some simple steps that families can take that may have a positive impact,” said Rosen, the first author on the paper.

To assess the effect of pandemic stressors (including financial, health, social, school, and physical environment stressors) on children’s internalizing psychopathologies (such as anxiety) and externalizing psychopathology (such as behavioral issues), the group recruited 224 participants ages 7-15 and their caregivers from two ongoing longitudinal studies in the Seattle area and assessed their mental health through questionnaires disseminated in the spring of 2020 and the winter of 2020-21.

After creating a composite “score” of pandemic stressors to measure the cumulative effects of the different pressures on each child and their family, the researchers compared the answers given during the pandemic with earlier study results from the same children and determined the differences in reported psychopathology symptoms during the different study periods.

Those comparisons were the foundation for their recommendations.

Their study indicates that “having a structured routine, limiting passive screen time, and limiting news related to the pandemic, especially in younger children,” can be a positive influence on kids’ mental health, said Rosen. “To a lesser degree, spending time in nature and getting enough sleep may also be beneficial.”

Strategies for caregivers

Less passive screen time

The researchers found that early in the pandemic, young people across the age spectrum who spent less time on the internet and digital devices exhibited lower internalizing and externalizing psychopathology symptoms. Six months later, they found that children who had more screen time displayed higher internalizing psychopathology.

The same was not true for adolescents, but despite this, the researchers recommended less passive screen time for children of all ages during and after the pandemic.

“One reason that youths with lower screen time use may be buffered against pandemic-related increases in psychopathology is because they are engaging in other behaviors that promote well-being such as getting sufficient sleep, among others,” the authors wrote. “Together, these findings suggest some potential benefits associated with limiting passive screen time among youth during the pandemic.”

Less news consumption

The group’s findings suggest a correlation between consuming media news about the pandemic and higher levels of externalizing and internalizing psychopathology, particularly during the early months of the pandemic.

However, this connection was dependent on age. At the beginning of the pandemic, adolescents who consumed more news (more than two hours per day) showed a reduction in externalizing symptoms of psychopathology. Six months later, they displayed a weaker association between pandemic stress and internalizing psychopathology compared with youth who consumed less news (less than two hours per day).

“It is possible that for adolescents, having more knowledge about the pandemic early on may have been beneficial over time,” the researchers wrote.

News consumption did not appear to reduce psychopathology in younger children, leading researchers to suggest that parents should ration younger children’s pandemic news consumption and instead talk to them about what is happening, taking care to listen to their concerns and respond in an age-appropriate way.

Structured daily routine

Youths of all ages who had a structured daily routine displayed lower externalizing symptoms six months after the start of the pandemic, compared with children with less structure in their daily lives.

Using evidence from earlier studies suggesting that youth psychopathology is linked to a lack of predictability in daily life, the researchers recommended more structure for children of all ages as a positive approach to building resiliency.

“Although maintaining routine and structure is challenging,” due to changes in school schedules and other unpredictable aspects of daily life, the authors wrote, “creating a structured daily routine for children and adolescents may promote better mental health during the pandemic.”

As COVID-19 deaths in the nation top 225,000, President Trump continues to downplay the severity of the pandemic, belittle government infectious disease experts such as Anthony Fauci, and display a cavalier attitude at times toward key public health measures like wearing face masks, despite having contracted the virus himself, along with about two dozen in his inner circle.

Public health officials say that Trump’s attitude undermines their efforts to get Americans to embrace safety guidelines to prevent spread of the disease. “Whether it is his intention or not, the consequence is that he’s undermining scientific authority, trust in science, and trust in scientists,” said K. “Vish” Viswanath, Lee Kum Kee Professor of Health Communication at Harvard T.H. Chan School of Public Health (HSPH). “We know from our data and other data that the greater the trust in scientists and researchers, the greater the likelihood of compliance with public health mitigation measures.”

Trump’s remarks also set Robert Hahn, Ph.D. ’76, to thinking. He’d heard the president blithely suggest disinfectants, UV light, and hydroxychloroquine as potential COVID treatments during White House briefings in April. The veteran Centers for Disease Control (CDC) epidemiologist began wondering how Trump’s many scientifically unsupported pronouncements might be influencing public behavior, particularly with admirers. He was especially intrigued about the wearing of face masks because of how regularly the president questioned their efficacy and mocked those who wore them, despite that both the CDC and World Health Organization have urged their universal use.

“While I know there’s no direct evidence of how many people act in response to his statements, I wanted to try and quantify this,” said Hahn, who published his estimates in a new paper in the International Journal of Health Sciences.

Hahn estimates that as many as 12,000 COVID-related deaths can be attributed to Trump’s negative or false assertions about face masks, but he readily acknowledges that his results hinge on sets of assumptions of how much influence the president’s comments had on mask-wearing behavior.

Using population attributable risk, an epidemiological method that estimates the proportion of an outcome that is attributable to a given cause, Hahn examined reported COVID deaths between April 3, the first date Trump spoke about the CDC’s new mask recommendation (“It’s voluntary. You don’t have to do it”) and July 21, when he momentarily endorsed masks (“I will use it gladly. And I say: If you can, use the mask”) before scorning them again and periodically forgoing them.

With much of the world still susceptible to SARS-CoV-2, experts predict the virus will become endemic.

The Harvard T.H. Chan of Public Health asked immunologist Yonatan Grad what it will look like as COVID-19 continues to circulate in the months and years ahead. Grad is the Melvin J. and Geraldine L. Glimcher Associate Professor of Immunology and Infectious Diseases at the Chan School.

Q&A

Yontan Grad

HARVARD CHAN SCHOOL: Many experts have said they expect COVID-19 to become an endemic disease. How does a disease go from being acute to endemic? What factors shape the transition to endemicity? What’s a likely timeline for COVID-19 to become endemic?

GRAD: The expectation that COVID-19 will become endemic essentially means that the pandemic will not end with the virus disappearing; instead, the optimistic view is that enough people will gain immune protection from vaccination and from natural infection such that there will be less transmission and much less COVID-19-related hospitalization and death, even as the virus continues to circulate.

The expected continued circulation of SARS-CoV-2 stands in contrast with the first round of SARS in 2003 and with the Ebola virus outbreak in West Africa in 2014, when public health measures ultimately stopped spread and brought both outbreaks to an end. While there are important differences among the viruses and the contexts, this comparison underscores the critical need to improve our global public health infrastructure and surveillance systems to monitor for and help respond to the inevitable next potential pandemic virus.

Since viruses spread where there are enough susceptible individuals and enough contact among them to sustain spread, it’s hard to anticipate what the timeline will be for the expected shift of COVID-19 to endemicity. It’s dependent on factors like the strength and duration of immune protection from vaccination and natural infection, our patterns of contact with one another that allow spread, and the transmissibility of the virus. So the patterns will likely differ considerably from what we saw with the other pandemics because of the heterogeneous responses to COVID-19 across the world — with some places engaging in “zero-COVID” policies, others with limited responses, and widely variable vaccine availability and uptake.

HARVARD CHAN SCHOOL: What does history tell us about how deadly viruses such as COVID-19 can, over time, become manageable threats?

GRAD: We know of a few respiratory viruses that were introduced into the human population, swept across the globe, and transitioned to endemic circulation, usually with annual wintertime peaks in incidence. The example most commonly invoked these days is the 1918 flu pandemic, caused by an A/H1N1 influenza virus. But there are other more recent examples from influenza: The 1957 flu pandemic caused by an A/H2N2 influenza virus, the 1968 flu pandemic from an A/H3N2 influenza virus, and the 2009 “swine flu” pandemic, from an A/H1N1 influenza virus.

The pandemics generally began with infection fatality rates higher than observed in the years following their introduction as the viruses continued to circulate. While declining fatality rates after pandemics may be due to a number of factors, one likely key contributor is that the first round of exposure to a pathogen confers some degree of protection against reinfection and severity of disease if reinfection does occur. Vaccines confer protection in much the same way, as the data from the COVID-19 vaccines has demonstrated.

HARVARD CHAN SCHOOL: What is the likelihood that we will need booster shots every year?

GRAD: The need for annual boosters isn’t clear, and key biology and policy questions remain to be answered. On the biology side, how much antigenic evolution will we see in SARS-CoV-2 — in other words, to what extent will it evolve to evade our immune system? We know of examples on both ends of the spectrum — some viruses, like influenza, require repeated vaccination because of its antigenic evolution, whereas others, like measles, are kept at bay for decades after childhood vaccination. How long does immune protection last, and what is the nature of that protection? How much does vaccine-conferred protection reduce the likelihood of infection, of severe disease if infected, or of the likelihood of transmission if infected? How quickly do each of these responses wane? On the policy side, what burden of disease are we willing to tolerate in a population?

These policy questions extend beyond COVID-19, of course, and should prompt us to reevaluate what we want to do about other preventable diseases. We’re in the midst of a wave of respiratory syncytial virus (RSV), another respiratory virus that for most of us causes cold and flu-like symptoms but that can be much more severe in infants, the elderly, and those with respiratory conditions. We don’t yet have an approved vaccine or highly effective treatment for RSV. And while we have modestly effective influenza vaccines and therapeutics, we usually see between 20,000 to 60,000 deaths a year in the U.S. from influenza. On a global scale, tuberculosis and malaria remain scourges that cause immense suffering. Investments in these areas and other measures that we’ve learned from COVID-19, such as the importance of ventilation and masking, can help reduce illness and death from a range of respiratory viruses and drive innovation in tools to tackle other infectious disease threats.

Past pandemics have led to massive changes in the way we live that we’ve come to accept as normal. Screens on our doors and windows helped keep out mosquitos that carried yellow fever and malaria. Sewer systems and access to clean water helped eliminate typhoid and cholera epidemics. Perhaps the lessons learned from COVID-19 in terms of disease prevention can yield similar long-term improvements in individual and global health.

Thousands of COVID-19 cases and deaths in California, Oregon, and Washington between March and December 2020 may be attributable to increases in fine particulate air pollution (PM2.5) from wildfire smoke, according to a new study co-authored by researchers at Harvard T.H. Chan School of Public Health.

The study is the first to quantify the degree to which increases in PM2.5 pollution during the wildfires contributed to excess COVID-19 cases and deaths in the U.S. It will be published online Friday in Science Advances.

“The year 2020 brought unimaginable challenges in public health, with the convergence of the COVID-19 pandemic and wildfires across the western United States. In this study we are providing evidence that climate change — which increases the frequency and the intensity of wildfires — and the pandemic are a disastrous combination,” said Francesca Dominici, the Clarence James Gamble Professor of Biostatistics, Population and Data Science at the Harvard Chan School and senior author of the study.

In 2020, huge wildfires swept across the western U.S., including some of the largest ever in California and Washington. Wildfires produce high levels of fine particulate matter, which has been linked with a host of negative health outcomes, including premature death, asthma, chronic obstructive pulmonary diseases (COPD), and other respiratory illnesses.

The researchers — from the Harvard Chan School, the John A. Paulson School of Engineering and Applied Sciences, and the Environmental Systems Research Institute in Redlands, Calif. — built and validated a statistical model to quantify the extent to which wildfire smoke may have contributed to excess COVID-19 cases and deaths in the three states that bore the brunt of the 2020 wildfires. They looked at the connection between county- and daily-level data on PM2.5 air concentrations from monitoring data, wildfire days from satellite data, and the number of COVID-19 cases and deaths in 92 counties, which represented 95 percent of the population across California, Oregon, and Washington. The researchers accounted for factors such as weather, population size, and societal patterns of social distancing and mass gatherings.

The study found that from Aug. 15 to Oct. 15, 2020, when fire activity was greatest, daily levels of PM2.5 during wildfire days were significantly higher than on non-wildfire days, with a median of 31.2 micrograms per cubic meter of air (µg/m3) versus 6.4 (µg/m3). In some counties, the levels of PM2.5 on wildfire days reached extremely high levels. For instance, on Sept. 14-17, 2020, Mono County, California, experienced four days in a row with PM2.5 levels higher than 500 µg/m3 as a result of the Creek Fire. Such levels are deemed “hazardous” by the U.S. Environmental Protection Agency.

Wildfires amplified the effect of exposure to PM2.5 on COVID-19 cases and deaths for up to four weeks after the exposure, the study found. In some counties, the percentage of the total number of COVID-19 cases and deaths attributable to high PM2.5 levels was substantial.

On average across all counties, the study found that a daily increase of 10 µg/m3 in PM2.5 each day for 28 subsequent days was associated with an 11.7 percent increase in COVID-19 cases, and an 8.4 percent increase in COVID-19 deaths. The biggest effects for cases were in the counties of Sonoma, California, and Whitman, Washington, with 65.3 percent and 71.6 percent increases, respectively. The biggest effects for deaths were in Calaveras, California, and San Bernardino, California, with 52.8 percent and 65.9 percent increases, respectively.

Researchers also looked at individual wildfire days and at individual counties to determine the percentage increase in COVID-19 cases and deaths in 2020 compared with what would have been expected with lower levels of PM2.5. They found that Butte, California and Whitman, Washington, had the highest percentage increases in cases (17.3 percent and 18.2 percent, respectively); and that Butte, California, and Calaveras, California, had the highest percentage increases in deaths (41 percent and 137.4 percent, respectively.) In Calaveras, roughly nine COVID-19 deaths would have been expected under lower PM2.5 levels, but the actual number was 22 — which explains the high percentage increase.

Across the three states studied, the cumulative numbers of COVID-19 cases and deaths attributable to daily increases in PM2.5 from wildfires were 19,700 and 750, respectively, the study found.

“Climate change will likely bring warmer and drier conditions to the west, providing more fuel for fires to consume and further enhancing fire activity. This study provides policymakers with key information regarding how the effects of one global crisis — climate change — can have cascading effects on concurrent global crises — in this case, the COVID-19 pandemic,” said Dominici.

Co-first authors of the study were Xiaodan Zhou of the Environmental Systems Research Institute and Kevin Josey from the Department of Biostatistics at the Harvard Chan School. Leila Kamareddine of the Department of Biostatistics at the Harvard Chan School also contributed, as did Miah C. Caine and Loretta J. Mickley from Harvard’s John A. Paulson School of Engineering and Applied Sciences, and Tianjia Liu from Harvard’s Department of Earth and Planetary Sciences.

Funding for the study came from the Environmental Protection Agency (grant 83587201-0), the National Institutes of Health (grants R01ES026217, R01MD012769, R01ES028033, 1R01AG060232-01A1, 1R01ES030616, 1R01AG066793-01R01, 1R01ES029950, and 5T32ES007142), the Alfred P. Sloan Foundation, and the Vice Provost for Research-Harvard University.