Here we sort out some of the key concepts, history and background of the novel coronavirus, SARS-CoV-2019, and COVID-19.

Breakthrough infection and COVID-19

Community transmission rate and COVID-19 hot spots

Contact tracing

Containment versus mitigation

Controversy over airborne transmission of COVID-19

COVID-19 Vaccine Surveillance and misinformation

Disease elimination vs. eradication

Disease X

Endemic COVID-19

Epidemiologic triangle

Flattening the curve

Hand hygiene – Health care settings and non-health care settings 

Immune response and the coronavirus

Infectious disease modeling

Inflammatory syndromes

One Health

Outbreak culture

Pool testing

Quarantine and isolation


RNA vaccines - how they work, in brief

SARS-CoV-2 variants

Super spreader

Test to Stay


Wastewater surveillance

Breakthrough infection and COVID-19 

In public health, a breakthrough case or infection happens when a fully vaccinated person later develops an infection from the pathogen they were vaccinated against.  

None of the three vaccines currently being used in the U.S. provide 100-percent protection against COVID-19, so breakthrough infections were expected. The Pfizer/BioNTech vaccine has an efficacy rate of 95 percent, meaning that someone who has the vaccine is 95 percent less likely to become infected than an unvaccinated individual. The Moderna has a 94 percent efficacy rate and the Johnson & Johnson has about a 72 percent efficacy rate.  

With COVID-19, the Centers for Disease Control and Prevention defines a breakthrough case as someone who tests positive for COVID-19 (with or without symptoms) 14 days or more after vaccination. As of April 27, 2021, the CDC had reported more than 7,000 COVID-19 breakthrough cases among the more than 95.9 million who are fully vaccinated in the U.S., which suggests just a tiny percentage of people are experiencing such infections. The breakthrough case figures likely will continue to evolve as more of the population is vaccinated. 

Why some people experience a breakthrough infection remains a subject of investigation. It is possible that some were exposed to a variant of the virus that can evade the defenses that the vaccine helps the person’s immune system develop. Public health officials have said the breakthrough cases that have occurred so far were expected and not a cause for alarm. Early data indicate that someone who has become infected after vaccination experience a less severe form of the illness and are at significantly less risk of death than someone who isn’t vaccinated. 

Breakthrough cases also occur with diseases like influenza. Note that the typical yearly flu shot has an efficacy rate of around 40%–60% annually.

Community transmission rate and COVID-19 hot spots

As part of public health measures aimed at reducing spread of COVID-19, the World Health Organization recommends that communities aim for a positivity rate of less than 5 percent for at least two weeks. A threshold of 5 percent or more could be an indication that the spread of COVID-19 is not under control in the community.

If COVID-19 transmission is decreasing and more people are being tested, including those who are not infected, the positivity rate should be falling or remain below 5 percent, according to the Kaiser Family Foundation. In communities where the positivity rate is rising, either an insufficient share of the population is being tested and/or COVID-19 cases are increasing. It is possible that in these places, the number of new cases is increasing at an even faster rate than the confirmed case counts suggest. In addition, a positivity rate of 10% or more indicates the likelihood that there are a relatively high numbers of cases and an ongoing epidemic in the state.

The U.S. Centers for Disease Control and Prevention outlines criteria [the basic reproduction number of the virus, the infection fatality ratio, and pre-symptomatic and asymptomatic spread] for public health leaders in communities to use to determine policies for community mitigation measures. The agency cautioned that because of the unknowns about the virus, it expects its criteria to be continually updated. The agency doesn’t publicly list a transmission rate threshold.

Private organizations, such as the Kaiser Family Foundation and Johns Hopkins University & Medicine Coronavirus Resource Center have been keeping tabs on positivity rates in states to help citizens understand, on a national level, which communities may have COVID-19 spread in check and which do not. As of mid-August, at least 33 states were considered hot spots with positivity rates of 5% or more over a seven-day period.

Contact tracing

Contact tracing is a monitoring process used to stop the spread of an infectious disease outbreak.

The process is a bit like detective work. Individuals are trained to interview those diagnosed with a contagious disease and learn who they may have recently been in contact with and potentially infected. Those individuals, in turn, may be asked to quarantine themselves to prevent further spread.

Contact tracers find the index patient, and then learn about the circle of individuals who may have been exposed and infected, as well as those who were not infected by the person. By building a “ring,” around the individual, public health officials can then seal off the contagion and prevent transmission of the pathogen to others in the community.

Contract tracing was deployed at the beginning of the COVID-19 outbreak. Federal, state and local public health officials tried to build a ring around those individuals who were sick and tested positive for the SARS-Cov-2, the COVID-19 virus. However, because the pathogen spread via individuals without symptoms, and there was no testing of those without symptoms, contact tracers were unable to manage the virus's spread in the community.

Social distancing - the requirement that people remain at home and at least six feet apart from one another in public - has been the only current tool that has effectively slowed the spread of SARS-Cov-2.

Until there is a vaccine and effective treatments, states and cities are looking into using contact tracing as a means for enabling leaders to lift social distancing measures.

Once there has been a sustained decline in new cases and deaths, here is how contract tracing would work: once someone has been confirmed infected through a positive COVID-19 test, a contact tracer would track down all the individuals who may have been in prolonged exposure with the infected person. Prolonged exposure means being within less than 6 feet of the infected person for between five and 10 minutes, Dr. Laura Breeher, medical director of occupational health services at the Mayo Clinic told Time magazine.

Once those individuals were identified, they each would be warned of their exposure and advised to quarantine, so not to spread the virus to others.

“Contact tracing, it’s having a moment of glory right now with COVID because of the crucial importance of identifying those individuals who have been exposed quickly and isolating or quarantining them,” Breeher said.

Contact tracing takes a lot of time and manpower, however. Interviewing and reaching out to patients takes lot of effort and relies on people answering their phones and being willing to accept they may have been exposed and willingness to self-quarantine. Technology can be used to help with the labor. Some countries are using cell phone data, and Google and Apple are investigating how to add software to smart phones that could be used to augment tracing.

So far, efforts to build contact tracing efforts have been piecemeal, with cities and states acting on their own. Massachusetts, for example, is spending $44 million to hire 1,000 people, who not only will track people down, but are to be trained to offer support, give advice and help arrange assistance for food and housing. San Francisco is hiring 250 people to become outreach workers and contact tracers.

The Centers of Disease Control and Prevention has said it has 600 people deployed across the country as contact tracers, but for monitoring process to be effective, Johns Hopkins Bloomberg School of Public Health's Center for Health Security estimates that the country needs 100,000 people across the country to work.

To be done effectively, contact tracing requires people with the training, supervision, and access to social and medical support for patients and contacts. Requisite knowledge and skills for contact tracers include, such criteria as: an understanding of patient confidentiality, including the ability to conduct interviews without violating confidentiality, an understanding of the medical terms and principles of exposure and infection and excellent and sensitive interpersonal, cultural sensitivity, and interviewing skills. See more from the CDC here.

Contact tracing doesn’t work unless there are quick and accurate COVID-19 tests available to everyone, so that contact tracers know who to reach out to.

As of late April, the U.S. has been testing about 146,000 people a day, but it needs to be closer to 500,000 to 700,000 a day to ensure that there isn’t a spike in new illnesses and death.

Absent a vaccine and effective medical treatments, until there is a widespread testing and the workforce available to carry out contact tracing, social distancing is going to remain the most effective measure for keeping the virus in check.

Containment versus mitigation

During a fast-moving infectious disease outbreak, public health officials respond with tools to stop its spread. First they try measures aimed at containing the disease, and if that doesn’t succeed, they move to reduce the severity of illness with mitigation efforts.

Containment and mitigation tools differ depending upon the kind of infection that is spreading, and the availability of medical treatments and vaccines. With a known disease, it is easier to stop an outbreak. Containment tools include vaccinations, contact tracing and quarantines.      

With a disease with no medical treatment option, as is the case with COVID-19, public health officials must find non-pharmaceutical methods for reducing the severity of the outbreak. These measures can include mitigation efforts such as quarantines, social distancing and banning gatherings of large numbers of people.

When there is a rapidly evolving outbreak, as there has been with COVID-19, U.S. officials first worked to contain its spread by restricting travel into the U.S. from China, where the virus first emerged. As the virus spread to other countries, like South Korea and Iran, the U.S. restricted travel from these countries as well. The restrictions included limiting non-U.S. citizens from entering the U.S. and requiring those that had recently traveled to these countries, to quarantine themselves, or to undergo monitoring by officials from the Centers for Disease Control and Prevention.

The CDC and state and local public health officials also aggressively followed up with contract tracing with passengers who traveled to China and became ill after returning home. They advised those who came in contact with the individual who had traveled to quarantine themselves at home also.

“In general, containment means that you stop the spread,” Nancy Messonnier, M.D., director of the CDC’s Center for the National Center for Immunization and Respiratory Diseases., explained to reporters on March 9, 2020. “What [containment] has meant in this [outbreak] is decreasing the number of potentially exposed people coming into the US through border control and then tracking every case and every potential contact, every case in order to keep them from spreading it further.

The CDC’s efforts to contain COVID-19 has been hampered by the inability to test large numbers of people. In about 80 percent of cases, those infected with COVID-19, which spreads easily through respiratory droplets, doesn’t cause any symptoms, but may still be contagious.

It is likely therefore, that many Americans traveled overseas, came in contact with someone infected, and then unknowingly brought the virus back home.

By early March, the U.S. Surgeon General acknowledged that federal efforts to contain COVID-19 in the U.S. didn'tT work. There was community spread - meaning that cases of the disease had emerged in people across the country, who never traveled to places outside the U.S.

On March 13, President Trump declared a public health emergency and within days, states and cities implemented the strictest social distancing measures in modern history. All non-essential businesses were ordered closed and people were urged to stay home. Gatherings involving more than ten people were banned, including religious gatherings. People were warned to remain within six feet of one another if they had to be in public.

These mitigation steps have likely slowed the spread of COVID-19, but not stopped it.  As of April 20, COVID-19 had infected 772,524 and killed 37,321, according to the COVID Tracking Project

Controversy over airborne transmission of COVID-19

Airborne transmission is defined as the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in air over long distances and time. 

SARS-CoV-2, the coronavirus that causes COVID-19, reproduces in our upper and lower respiratory tracts, and is emitted, via these droplets, when we breathe, talk, sing, cough, or sneeze.  Understanding how much and how far these droplets spread is key to controlling the pandemic. 

In May 2021, the Centers for Disease Control and Infection, updated its guidance to explicitly state that one of three ways that people can be infected by the virus includes airborne transmission, especially in enclosed spaces with poor ventilation and from someone who is more than 6 feet away. The other two routes are respiratory droplets and touching an object contaminated by the virus.  

This has been a topic of vigorous debate among scientists since the beginning of the pandemic.  In July 2020, hundreds of scientists published a paper urging the World Health Organization and other health agencies to recognize the airborne threat of SARS-CoV-2. But for a variety of reasons, including the challenge of developing guidance on ventilation measures, they did not. 

There also wasn’t enough evidence for public health officials to be sure that it was a key route of transmission. 

Scientists were confident that certain medical procedures, like inserting a tube in an infected individual’s trachea, generates droplets that spread in the air. This is called an “aerosol generating procedure.” It is why medical personnel must wear personal protective equipment when caring for an individual with COVID-19. 

The disagreement was outside the clinical setting. Scientists disagreed about how many droplets an infected person generates and how and where they travel. 

It all comes down to the size of these infectious droplets, according to this Atlantic story.  Bigger droplets may be pulled down to the ground by gravity. Smaller ones might float around. Until the past few months, both the CDC and the World Health Organization said they believed the main route of COVID-19 transmission was respiratory droplets. Bigger respiratory droplets, say 5 to 10 microns in diameter, fall to the ground – on average, within six feet. This is how the six feet social distancing measure came to be. By staying more than six feet away from an infected person, scientists believed a person could protect themselves from becoming infected.  

But an accumulating amount of evidence over the past year demonstrated this was not the case and that some people who stayed more than 6 feet from an infected person could become infected. The risk of COVID-19 transmission is now considered to be both from respiratory and aerosolized droplets. 

The CDC said the change in guidance was made to reflect current knowledge about SARS-CoV-2 transmission.

COVID-19 Vaccine Surveillance and misinformation

As more and more Americans are getting COVID-19 vaccines, the Centers for Disease Control and Prevention is tracking side effects through a smart-phone based application called “V-Safe.” 

The most common symptoms that have been reported include fatigue, muscle and joint pain, fever, redness, and swelling at the injection site, skin rashes and headaches. The V-Safe program is an addition to the CDC’s long-standing vaccine tracking program called the Vaccine Adverse Event Reporting System. VAERS was created in 1990 and is a voluntary surveillance system, monitored by the CDC and the U.S. Food and Drug Administration, and available for anyone (doctors, patients, parents, other health care providers, etc.) to report any adverse event that occurred after receiving a vaccine. 

VAERS data is public and can be downloaded, but journalists should be mindful that the VAERS system is an unverified reporting system, and the reports in VAERS don’t mean that the symptoms reported are caused by the vaccines.

Disease elimination vs. eradication

The elimination of rubella in the Americas was announced in April 2015, followed by the elimination of measles across the Americas continents in September 2016. Yet measles cases still occur in North and South America, and news is still being reported on the eradication of polio, which has not been seen in the Americas in years. The key here is that “elimination” and “eradication” are different things, though they are often confused by readers and sometimes even by journalists.

Eradication refers to a disease being completely, literally eradicated from the earth: no cases occur at all, from any source. The best-known example is the eradication of smallpox in 1980. Another lesser known disease that has been eradicated includes the livestock virus rinderpest. Campaigns to eradicate polio and Guinea worm are officially underway, and it could be argued that public health officials are — so far unofficially — working toward eradication of hookworm, measles, rubella, malaria and other diseases.  Only certain conditions are able to be eradicated with current tools. An example would be a disease which lives in the environment, rather than requiring a human vector.

Elimination, however, refers to a permanent interruption in indigenous transmission of a disease, making it no longer endemic, but the disease can still be introduced by a case from another geographical region. Or, as it was put in an article about the measles elimination, “Measles no longer lives in the Americas though it occasionally visits.” For example, measles has been eliminated from the U.S. since 2000, but there have been a number of measles outbreaks in the U.S. since then. All of those outbreaks, however, were introduced by a person visiting from outside the U.S. None of them began with a person already living in the U.S. because the virus no longer circulates on its own in the U.S., thanks to the effectiveness of the measles vaccine.

The distinction is important because an eliminated disease can always return if conditions allow for it, such as a sufficiently deep, sustained drop in immunization rates that allows measles to begin circulating again.

Disease X

When infectious disease experts are asked about which disease everyone should be worrying about, after the influenza virus, they often answer “Disease X.”

Disease X, stands for an unknown bacteria or virus that might be lurking in animals or humans, with the potential to suddenly become virulent and contagious, spreading around the world. As Wired magazine put it, “Disease X is a contagion requiring immediate attention- but which we don’t yet know about.” And because we don’t know about it, there is no treatment or vaccine for it.

“Disease X” emerged on infectious disease experts’ minds after the World Health Organization named it as one of eight pathogens that public health officials believe is of high risk to blow up into an epidemic. The WHO list, called the “Blueprint Priority Diseases” and was developed to spur research investment in finding vaccines, treatments and medical counter measures for these pathogens, where few or none currently exist.

On the list includes Ebola, other hemorrhagic fevers, Middle East Respiratory syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), mosquito-born diseases Zika and Rift Valley Fever, and now Disease X.

Though there is no “Disease X” per se, the WHO’s inclusion of it was meant to remind public health leaders and healthcare providers to be ready for any new and dangerous emerging illness. Recent history is a guide of how that can happen. The WHO declared a public health emergency to respond to three unexpected outbreaks in the past decade, including the swine flu pandemic in 2009, the Ebola virus outbreak in West Africa in 2014, and the Zika virus in 2016.

The WHO’s list has spurred investment in vaccine research in the form of the Coalition for Epidemic Preparedness Innovations, a joint public and private organization funded by Norway, Germany, Japan, the Bill & Melinda Gates Foundation and the Wellcome Trust. The effort has so far raised $630 million towards its goal of reaching $1 billion in vaccine research investment.

One effort the organization is looking at is developing a universal vaccine platform that could be used to quickly, in the event of an emergency, tailor vaccine production, based on the genomic sequence of the pathogen.

In the U.S., public health officials are better prepared than five years ago to handle a health emergency like a “Disease X,” but regional gaps remain, the Robert Wood Johnson Foundation said in a 2018 report.

Endemic COVID-19

When an infectious disease is endemic, it means that the disease is constantly circulating in a population, but cases are neither rising nor falling. Malaria, for example is endemic in many African, South American and South Asian countries, and kills around 600,000 people a year. 

Scientists expect the virus SARS-CoV-2 to become endemic, meaning it will always be circulating like influenza and cold viruses. What scientists don’t know is whether or not COVID-19 disease (caused by SARS-CoV-2) will become less prevalent and deadly or whether the virus will continually mutate to develop variants that evade vaccines and cause large waves in cases as well as disease.

There has been a misperception that as this pandemic moves to an endemic phase, Americans will no longer have to worry about COVID-19. That is not the case. It may be that we will be dealing with returning mask mandates, social distancing and boosters vaccine shots for many years to come, if there are repeated large waves of cases.

Epidemiologic triangle

To understand how an infectious disease spreads, public health officials ask questions reminiscent of journalists. They want to know: What was the agent that caused the disease? Who was the host? Where did the transmission occur? These three questions create the “Epidemiologic Triangle” model, which is used to determine the nature of an outbreak.

To end the outbreak, epidemiologists seek to answer at least one of the “sides” of the triangle.

Question one: “What is the agent?” refers to the microbe  — a bacteria, virus, fungi or parasite  that is causing the disease. How did it invade, leave or transmit to the host? Was the transmission direct (from a person coughing on another person)? Or indirect? (from eating contaminated food, or drinking dirty water?) Or through an animal or insect? (from the bite of a mosquito?)

Question two: “Who is the host?” refers to the human or animal that is exposed and harboring a disease. What was the risk, or the susceptibility of the person of getting the disease? The answers to the questions may be biological (do they have a genetic predisposition for the disease? Or a weak immune system?), behavioral (what are the person’s eating habits?), demographic or cultural (do they have access to clean water? Do they live on a farm?)

Question three: “Where did the transmission occur?” refers to the environment. The environment impacts the risk of an animal or person’s exposure to a pathogen. For example, what is the climate, geology, and habitat of the person or animal? Is the person living in a nursing home? What is the biological environment? Does the person live near a jungle or river, where there are mosquitos? And what is the person’s economic status? What is their occupation? Was there a natural disaster, like a hurricane, which caused mold to grow? Other environmental factors include the weather. In the winter, flu viruses spread more quickly, than in the warm summer months.

In the middle of the triangle is time. It is the period between exposure and signs of symptoms, which is called the incubation period. The time can provide information to epidemiologists about the nature of the pathogen, its source and identify those who were likely infected.

These are all questions journalists may ask public health officials as well when they are covering a disease outbreak and want to know more about what it means for their community.

Flattening the curve 

In epidemiology – the study of disease – it is a term used to refer to the curve in the projected number of people who will contract a pathogen over a period of time. If models are showing that the pathogen is expected to infect people quickly, the curve upward is sharp. So public health officials look for ways to slow the spread the pathogen, or flatten that curve, to prevent hospital systems from becoming overwhelmed with patients.

The term has now become part of the American lexicon as government leaders and public health officials have sought to explain why strict social distancing measures are being enacted to stop the spread of SARS-CoV-19, the virus that causes COVID-19.

When someone is infected with COVID-19, that individual can spread it, on average, to between two and three people. For that reason, there is a sharp upward curve of disease models detailing how quickly the COVID-19 can spread, if nothing is done to slow its transmission. The virus is most likely transmitted through close personal contact and potentially from touching contaminated surfaces.

 Because there is no vaccine or specific medication to treat COVID-19, the only option to slow the transmission rate, and flatten the infection curve, is through collective social distancing, which means, avoiding other people whenever possible.

On March 16, the Imperial College of London, predicted that unless there was enforced social distancing in the US population, 2.2 million Americans could die.

History has shown this works. John Barry, who wrote “The Great Influenza” about the 1918 Spanish flu pandemic, details the tale of two cities, Philadelphia and St. Louis, and how their public health approaches when the flu began to circulate in their communities, impacted mortality rates. In Philadelphia, city officials permitted a massive parade and kept most businesses open. Within two to three days, thousands of people in that city began to die. In St. Louis, city officials closed schools, limited travel and encouraged social distancing. The city experienced far fewer deaths.

Social distancing has also been part of US public health officials’ pandemic planning. In 2007, the CDC published a paper for community mitigation strategies to respond to a fast-moving respiratory pandemic, like COVID-19. The graph in the paper is similar to the one that has been circulating in the past several months, as public health officials explain “flattening the curve.”

Fast Company detailed how the CDC paper remained obscure until it began to circulate on Twitter in early 2020. See the story here.

Hand hygiene – Health care settings and non-health care settings

Washing ones hands is among the most effective ways of reduction the spread of infections.

In health care settings, those providing services wash their hands less than half the time that they should, which contributes to the spread of disease in hospitals where patients are already sick. On any given day, at least 31 patients have gotten an infection because someone working at the hospital touched them with a pathogen on their hands, according to the Centers for Disease Control and Prevention.    

The CDC recommends health care providers use an alcohol-based sanitizer on their hands immediately prior to touching a patient and to wash their hands with soap and water if their hands are visibly soiled. The agency also recommends using sanitizer before handling medical equipment, before moving from work on a soiled body site to a clean site on the body, after touching a patient’s immediate environment and after removing gloves. They also say providers should wash their hands with soap and water after touching a patient with diarrhea or suspected exposure to a spore, like c. difficile.

In non-clinical settings, the CDC recommends everyone wash their hands at certain times to prevent disease. They recommend doing so before, during and after preparing food, before eating, before and after caring for someone who is sick, before and after treating a wound, after using the toilet, after changing a diaper, after blowing your nose, or coughing, after touching a pet and after handling garbage. Proper hand washing includes wetting the hands, putting on soap, and scrubbing hands for at least 20 seconds, rinsing hands and then drying them with a clean towel or letting them air. If soap and water aren’t available, the Food and Drug Administration recommends using hand sanitizer, however, the agency says hand sanitizer should be a second option. As of April 2019, the FDA is studying hand sanitizer chemicals to ensure their safety.

Immune responses and the coronavirus

Scientists are still trying to understand why some people become so sick from SARS-CoV-2, the virus that causes COVID-19, and why some people don’t. But scientists say it is increasingly clear that it is a combination of individuals’ immune system responses, their DNA and their age that cause such varying responses. In some people, the coronavirus causes their immune system to go haywire, as Elemental journalist Dana Smith explains so well in this story. Specifically, scientists are learning that in some people, the body has some kind of malfunction with regard to the development of T-cells, which play a key role in fighting pathogens. This story and this story explain the phenomenon and how the coronavirus causes the immune system to get out of balance. As individuals age, the immune system’s ability to quickly produce T-cells may also wane, which may be a reason why SARS-CoV-2 has been more deadly for those 65 and older and why COVID-19 vaccines may not work as well for older adults, explains this New Yorker story. This November 2020 Science story goes even deeper about what is known and still unknown, with regard to T-cells and the role they play in the varying immune responses to the coronavirus causing COVID-19.

Infectious disease modeling

Despite great strides in medication, sanitation, hygiene and in animal and pest control, infectious diseases remain an enormous threat to human and animal health. Reemerging and new dangerous infectious diseases are surfacing around the planet at an accelerating rate. The number of total reported infectious disease outbreaks worldwide has tripled since 1980, according to the World Health Organization.

How these infectious diseases spread and become epidemics depends on a range of interconnected dynamics of pathogens, people and animals. Some microbes are transmitted between people, or between people and animals; some circulate among multiple hosts before they are transmitted, and others must be carried in an insect vector before spreading. Many factors including, increasing antibiotic resistance, human connectivity and behavior, population growth, climate change, land-use change, farming, urbanization and global travel, also impact the emergence and spread of infectious disease, as well as pose challenges for prevention and control.

Given these huge complexities, scientists have increasingly turned to mathematical models to understand epidemiological patterns to develop evidence for making public health decisions. These models all hark back to Isaac Newton, who had the fundamental insight that there are unchanging universal laws that govern the actions of natural phenomenon.  The hope is that with more data and more computing power, the most complex outcomes can be predicted.

In the past 20 years, growing computing power and infectious surveillance has enabled scientists to gather more data for developing these models. Researchers are collecting volumes of data from epidemiology, evolutionary biology, immunology, sociology, climate and public health resources to develop models that mimic how infections might evolve and spread.

The challenge with modeling infectious disease however, is that pathogens, the environment, the rate of contagiousness, the rate of transmission, the availability of vaccines, and the climate are ever changing. But most models rely on data from past events to predict the future.

Scientists are trying to develop models for specific pathogens that also take into account the likelihood of the many real-time variables. For example, utilizing information on social media to try to predict the magnitude of an upcoming flu season. These systems could quickly alert public health officials when there are too many instances of people complaining about a certain symptom, signaling a potential outbreak.

The Centers for Disease Control and Prevention, the National Institutes of Health, the U.S. State Department, private organizations like the EcoHealth Alliance, health systems, and other organizations are all working on developing these models.

The CDC funds the Epidemic Prediction Initiative which is monitoring dengue, influenza and mosquito activity as part of efforts to enhance the predictability of whether there will be a flare up of disease. The NIH is funding the Models of Infectious Disease Agent Study (MIDAS), which has supported projects ranging from the development simulation models of measles spread to Ebola outbreaks.

The CDC’s predictive flu project, called FluSight has been developing different mathematical algorithms matched with data collection – such an algorithm for data gathered through Google searches, or a model developed with data on flu-related hospitalizations. No one model has emerged as of yet, that is significantly better than another, say researchers.

Inflammatory syndromes

An inflammatory disease is when the immune system attacks the own body’s tissues, resulting in inflammation.

With COVID-19, the disease caused by the SARS-CoV-2 coronavirus, the immune systems in some adults, and, in rare cases, children, overreacts. Instead of protecting the body, the immune response makes the body sicker. In adults, the overactive immune system is called a “cytokine storm.” The body has two kinds of naturally occurring cytokines – ones that are pro-inflammatory, which send fighter cells to the parts of the body that have been invaded by a disease causing microbe, and anti-inflammatory cytokines, that tell the fighter cells to stand down. These two kinds of cytokines usually work together in balance.

For reasons that scientists don’t fully understand, some people’s inflammatory cytokines won’t stand down, resulting in a “cytokine storm.” With COVID-19, cytokine storms have resulted in patients needing help to breath through a ventilator. Scientists have learned that if they administer drugs to quell immune responses in COVID-19 patients on ventilators, it can reduce risk of mortality by 45%.

In rare cases, some children develop multisystem inflammatory syndrome (MIS-C) weeks after they were infected with SARS-CoV-2. Multiple systems become severely inflamed. Between March and May 2020, at least 186 children in 26 states, developed MIS, according to a July 2020 New England Journal of Medicine report. Though doctors don’t know why some children develop MIS, early data indicate the syndrome is associated with racial disparities. Around a third were children of Hispanic or LatinX descent and 25% were Black. MIS causes severe illness, requiring hospitalization in about 80 percent of those diagnosed. The NEJM report said 4% of those who developed MIS, died.

“It's unclear why some children who have COVID-19 develop MIS-C and others do not,” said Dr. Tina Tan, a pediatric infectious disease doctor at Northwestern University Feinberg School of Medicine. “So, there's no screening tests that can be done to determine who's going to develop MIS-C.”

One Health

One Health is a growing field within public health that embraces the connection between animals, humans and the environment and solve complex health problems such as emerging infectious diseases, food safety and antibiotic resistance.

The medical community observed that human and animal health were closely linked back in the late 1800s, but the concept of One Health has risen in prominence as the world’s population has exploded. By 2025, there are expected to be more than 8 billion people living on the planet, up from about 7.4 billion at the end of 2017.

Scientists estimate that more than 60 percent of all new emerging infections are a zoonosis, meaning they come from animals. Commonly known zoonoses include avian influenza, Ebola, rabies, Middle East Respiratory Syndrome and Lyme Disease. Worldwide, the number of infectious disease outbreaks has tripled. More than a dozen new infectious diseases have emerged over the past 25 years in the U.S. alone.

Outbreaks are associated with economic and agricultural turmoil. The 2014 outbreak of the Ebola virus, for example, cost Guinea, Liberia and Sierra Leone about $2.2 billion and a 2014 pathogenic avian influenza outbreak cost U.S. farmers about $3.3 billion.

Population growth is spurring antibiotic resistance. The increase in people is driving rising demand for animal protein, and an increase in animal production operations. In turn, antibiotics are being used on more animals, accelerating the rise of antibiotic-resistant bacteria, or “superbugs” in the environment. In the U.S., about 2 million people annually contract a superbug, and 23,000 die. By 2025, as many as 10 million people, could die annually as the result of a superbug infection, if humanity does nothing.

For all of these reasons, public health momentum surrounding One Health has grown. The U.S. Centers for Disease Control and Prevention created the first One Health office in 2009, to foster collaboration between international, federal, state and local governments, as well as the academic, health and private sectors.

As One Health is relatively new in the public health field, the definition of the term is imprecise. One Health has been defined as an initiative, a movement, a strategy, a framework, an agenda, an approach and a collaborative effort. In general, One Health involves the intersection of biology, comparative medicine, earth sciences, ecology, engineering, human medicine, social sciences, humanities and veterinary medicine. One Health programs link physicians, nurses, public health professionals, veterinarians, agricultural scientists, ecologists, social scientists, engineers, biologists and other professionals, to develop holistic solutions for keeping humans, animals and the environment healthy.

In the U.S., the CDC’s 10-person One Health office regularly coordinates discussions between the U.S. Department of Agriculture, the Department of Health and Human Services, the Interior Department, state health and agriculture departments, health systems, and health providers to discuss emerging infectious diseases that may impact communities.

Outbreak culture

Outbreak culture is a term to describe the collective mindset that develops within communities and by public health and humanitarian responders as a disease outbreak unfolds and the ways that the mindset can inhibit initial action and even worsen an epidemic. The mindset can develop from challenges in communication and coordination between individuals, agencies, organizations and governments, resistance by local people, uncertainty about the cause and source of a disease, health provider and infrastructure gaps, media coverage and politics.

Outbreak culture during the Ebola outbreak in West Africa in 2014 is detailed in a 2018 book: “Outbreak Culture,” co-authored by Pardis Sabeti, head of Sabeti Lab, a research group at Harvard University’s Faculty of Arts and Sciences Center for Systems Biology and journalist Lara Salahi.

Some of the examples of the challenges they describe include: lack of staff and medical equipment to treat Ebola, governments that didn’t want to admit to the world that there was an Ebola outbreak, communities that didn’t trust medical providers, communities that didn’t trust the government, government officials that tried to take over for local health providers, multiple humanitarian aide organizations that weren’t communicating with one another, and health care providers who weren’t sharing information with one another. Combined, these and other challenges likely led to more people being infected and dying from the Ebola outbreak than might otherwise, if an outbreak culture hadn’t developed.

To prepare for outbreaks in the future, Sabeti and Salahi suggest in their book that public health leaders focus on ways to enhance collaboration between individuals, providers, responders, communities and governments.

Among their suggestions is for the world to agree to the creation of a centralized governing structure that can step in during public health emergencies and make rapid decisions, in the vein of a military approach to a conflict. The leading global health governmental organization, the World Health Organization, cannot play that role because it is ultimately part of a diplomatic organization, the United Nations, they say.

Other suggestions include investing in building health infrastructures in resource challenged nations so that communities have more trust in providers and the government when there is an outbreak; developing systems for rapid sharing of information, data and medical samples during an outbreak and developing a unified approach to research during a public health emergency.

“We need to shift outbreak response to a mode that favors collaboration instead of competition and readiness instead of reaction,” say Sabeti and Salahi.

Pool testing

Back in May, German scientists published a paper explaining a testing strategy being used to catch cases of COVID-19 faster, called 'pool testing.' This method involves taking saliva or nose swabs from a group – or a pool – of people, and placing the samples into a single test tube.

Then one single test of that DNA collected into that test tube is run. If that test tube comes up negative, that means all 10 people aren't infected with COVID-19. If the test results come up positive, then each individual in that group is retested to determine who is infected.

Here is an example of how it would work: if a company had 100 people working for it, the company could break staff into 10 groups of 10 and run one test for each group. If none come back positive, then none of the 100 are infected. In this way, companies could run routine testing of their employees, while running many fewer tests, and keeping costs lower than would be the cost of running 100 individual tests.

Germany has found this strategy effective and now the U.S. is looking to adapt it, according to Anthony Fauci, M.D., the head of the National Institutes of Allergy and Infectious Disease.

The strategy could be of help in the U.S., where the testing landscape continues to face challenges. There remain shortages of swabs and reagents; machines can’t keep up with demand, and many places lack testing sites. It would also be a way to test for asymptomatic people. Catching the disease in asymptomatic people is important because a large portion of those infected either show no symptoms or take a few days to start feeling sick, but they can still spread the virus.

See the German research paper on pool testing here.

Quarantine and isolation

In the event of an outbreak of a contagious disease, health authorities may deploy several strategies to protect healthy people from getting sick, including implementing quarantines and isolation.

A quarantine involves restricting the moment of a person suspected of exposure to a communicable disease, even though the person isn’t yet showing any signs of illness, or doesn’t know if they might been exposed. The person is kept apart from the community until he or she can no longer transmit the disease to others. The time period of quarantine depends on the length of time a pathogen remains infectious.

Isolation involves separating someone who is already ill and removing them for anyone who isn’t sick, and keeping them apart until they are well. 

The history of quarantines goes back to the Middle Ages, when the plague was sweeping through Europe. Venice, a major port, tried to stop the disease from entering its city by requiring ships suspected of harboring plague, to wait offshore for 40 days before people or goods could come ashore. The city also built a hospital off its coast, where sailors who came off ships with the plague were sent. The forty-day waiting period was called “quarantinario,” for the Italian word for forty. Hence the word “quarantine.”

Quarantines can be important when there is no vaccine or drug to treat a rapidly spreading disease. They are, however, very controversial because they involve separating healthy people from the community, and they raise civil liberties questions. Forced quarantines and isolation can cause societal panic, as people worry about getting food, losing work, or becoming isolated from others.

Historically, quarantines have been used to target vulnerable populations in society, such as ethnic groups and the poor. In 2014, during the outbreak of Ebola (a viral hemorrhagic fever with no cure or vaccine), Liberia tried to impose a quarantine for 21 days (the incubation period for Ebola), causing people to flee into the jungle. The quarantine also sparked intense protests, leading the government to end the quarantine in ten days.

In the U.S., the federal government, through the Centers for Disease Control and Prevention, has the legal authority to quarantine and isolate a person, for up to 72 hours, at a U.S. airport, port or the border if the person is known to be infected or possibly infected with one of nine quarantinable diseases. The nine include: cholera, diphtheria, infectious tuberculosis, smallpox, yellow fever, viral hemorrhagic fevers, severe acute respiratory syndrome, new types of flu that could cause a pandemic, or a disease that has been designated by order of the President.

Health providers living in the U.S. who traveled to West Africa to care for Ebola patients in 2014, were asked to voluntarily remain at home and monitor themselves for any signs of illness during the 21-day incubation period. Ebola isn’t contagious until a person shows symptoms of illness. But some states when farther than the federal government during the outbreak.

Under emergency preparedness powers, every state, the District of Columbia and most territories have laws authorizing the use of quarantines and isolation, usually through the state’s health authority. Some states, including New York and New Jersey imposed forced quarantines upon some returning health care workers including Laura Skrip, a public health graduate student who had been in Liberia providing computer technology support during the outbreak. She was forced to stay in her apartment in isolation, enforced by a police officer patrolling her building.

The CDC has recently updated its community guidelines on quarantine in the event of a flu pandemic, which could provide guidance in future outbreaks of other diseases.


R0 (pronounced R-naught) is a number epidemiologists use to determine the infectiousness of a disease and a community’s susceptibility to an epidemic. The “R” stands for “reproductive number” and is a kind an epidemiological threshold. If the “R” number of a bacteria, virus, fungi or parasite, is greater than 1, the pathogen has a greater chance of spreading through a population and causing an epidemic. If it is less than one, then it is likely the disease will die out. If you want to geek out on the mathematical forumal, check out the Mathematical and Statistical Estimation Approaches in Epidemiology or this detailed description.

Understanding the susceptibility of a population is important for helping public health officials determine strategies for controlling the spread of an infectious disease, such as vaccinating the population or quarantining sick individuals if no vaccine is available.

The “R” number for a disease is a range and changes with conditions within the community at the time. Many factors impact the “R” number including the period of time for which a disease is contagious (the longer a person is contagious, the more likely the disease is to spread), the number of people that a sick person comes in contact with (a sick person who stays home may spread the disease more slowly), how the disease is transmitted between people (diseases that spread through the air, like measles can travel quickly, while those that are sexually transmitted spread more slowly), the immunity level of the population (whether people have been vaccinated for the disease or survived a version of the disease in the past) and whether there is a strong health and legal system within the community (hospitals to treat people and law enforcement to impose quarantines can reduce spread of a disease).

Ebola is a good example of how conditions within a community impact the “R” number. Ebola is spread between people by an infected person’s blood or bodily fluids. The World Health Organization says the average mortality rate from Ebola, is about 50 percent, but can range between 20 percent to 90 percent. The R number for Ebola is estimated around 1.5 to 2.5.

During the 2014 Ebola outbreak in West Africa, the R number was 1.51 in Guinea, 2.53 in Sierra Leone and 1.59 in Liberia. In Nigeria, the number was below 1, because as soon as one Ebola patient was identified, the country implemented a tracing program to isolate exposed individuals. There was no outbreak in the country.

Infectious diseases with R numbers that average above 1 include Hepatitis C (R2), Ebola (R2), HIV/AIDS (R4), Severe Acute Respiratory Syndrome (SARS) (R4), mumps (R10) and measles (R12-18) Healthline has a description and graphic here.

The R-naught number emerged into culture in the 2011 movie “Contagion” in which a virus causes a deadly epidemic in the U.S. Actress Kate Winslet plays a Centers for Disease Control and Prevention official who writes the R-naught formula onto a white board to try to determine how quickly the disease is spreading. Here’s an interesting Q & A from Wired magazine on the science behind the movie, which includes a conversation about the R-naught figure.

RNA vaccines - how they work, in brief

Under the federal COVID-19 vaccine effort called Operation Warp Speed, the two vaccines farthest along in the clinical trial process are RNA vaccines. One is produced by Pfizer, the other by Moderna.

Most conventional vaccines contain either an inactivated pathogen or the protein made by that pathogen called an antigen. With an RNA vaccine, just a piece of the pathogen’s genetic material is used to trigger the body’s immune response.

Pfizer and Moderna’s vaccines utilize RNA from the SARS-CoV-2 virus [the virus that causes COVID-19]. The RNA is injected into the body to trigger the production of SARS-CoV-2 antigens. Antigens are molecules that spur the body’s immune system to recognize a biological intruder. Once the immune system “sees” the SARS-CoV-2 antigen, the body produces antibody proteins. If the whole SARS-CoV-2 virus should enter the body, there are now existing antibodies to immediately mark the virus as an intruder, enabling the immune system to quickly mount a defense and thwart disease.

RNA vaccines aren’t made of the pathogen itself, so they aren’t infectious; they tend to be well-tolerated by the body, and they can be produced more rapidly than conventional vaccines.

To read more about RNA vaccines in greater detail, see this University of Cambridge link.

SARS-CoV-2 variants

At the center of the SARS-CoV-2 virus (which causes COVID-19) is a strand of 30,000 letters [which represent chemical properties] that make up its genome. To reproduce, the coronavirus, via a spike on its membrane, binds itself to the outside of a human cell and then enters it, hijacking the cell’s original genome, directing it to make copies of the SARS-CoV-2 virus instead.

Each time the SARS-CoV-2 virus reproduces, there is a natural possibility for a copying error in the letters, resulting in new variants of the virus. Most of the time, the copying errors are inconsequential or even weaken the ability of the virus to replicate. As the virus fights for survival, however, sometimes it mutates enough to make the pathogen more transmissible and potentially more lethal.

In September 2020, British scientists identified a lineage of the COVID-19 virus, called B.1.1.7 (named based on its phylogenetic tree), which had developed 17 mutations to its genome, 8 of which changed the shape of the virus’s spike, and seemed to make it more contagious. This strain has been spreading quickly through the United Kingdom. See this New York Times story digging into the mutations involved in B.1.1.7. The variant has now been found in 50 countries almost two dozen U.S. states. The Centers of Disease Control and Prevention warn this may become the dominant variant in the US by March this year.

The B.1.1.7 strain isn’t more deadly but because it is more infectious, this means more people could become and infected, and in turn, lead to more deaths. The strain has been found in 20 states, as of Jan. 20,  but the U.S., unlike the UK, doesn’t yet have a national surveillance system for genetic sequencing to determine where else in the country the virus might be spreading.

The CDC said scientists have identified two other concerning variants, though there is no evidence yet that they are circulating in the U.S. One, called P.1, was found in four travelers from Brazil who were returning to Japan, and the other, called 1.351 was found in South Africa in October 2020. Both have genetic codes that indicate they may be more transmissible than the original virus and have the potential to evade the body’s immune system.

Public health officials say there is no evidence yet that the variants will make the current COVID-19 vaccines less effective, but scientists will be watching to see if this remains true in the coming months as more people get vaccinated.

Super spreader

Someone who is infected with a particular disease and responsible for transmitting that bacteria or virus to a large number of other people. Epidemiologists say these are often the index cases where an epidemic begins.

Why someone is a "super spreader," depends on the kind of pathogen, the infected person's biology, their environment and their behavior at the given time. Today, with global travel, the ability to move pathogens rapidly across great distances, often before people are aware they are sick, creates environments ripe for super spreading.

Some infected people might shed more of a virus or bacteria into the environment than others because of how their immune system works. A person who is infected, but with no symptoms, may continue about their daily routines and inadvertently more people. A famous example of that type of person is "Typhoid Mary," a cook who supposedly infected 51 people with typhoid, even though she wasn't sick.

Alternatively, people who are sick may be very good at transmitting a pathogen even if they reduce their contacts with others. Individuals who have more symptoms – for example, coughing or sneezing more – can spread the disease to new human hosts. During the severe acute respiratory syndrome (SARS) outbreak, one sick traveler staying at a Hong Kong hotel spread the coronavirus to more than 100 others, some of whom were overseas travelers, who then took SARS to their home countries.

During an outbreak, epidemiologists look for super spreaders, because they can accelerate the rate of new infections in people.

Test to Stay

Test to Stay is a policy being utilized in K-12 schools to reduce disruptions of in-person learning during the pandemic. The CDC describes it as the practice of utilizing contact tracing and serial testing (testing twice during a seven-day period) to allow kids who were exposed to the virus in school and aren’t yet fully vaccinated to continue in-person learning during their quarantine period rather than having to take classes remotely or miss school altogether. Test to stay is one of multiple practices utilized by schools to reduce risk of spreading COVID-19 including contact tracing and masking. The test to stay policy was informed by three studies showing that using serial testing can minimize spread of the virus and allow a student to continue in-person studies safely. Many schools, however, have found the test to stay strategy challenging to implement because they don’t have adequate staff to administer tests or keep track of students’ test results.


While science continues to evolve on understanding how SARS-CoV-19 (the virus that causes COVID-19) is transmitted, early research does provide some information. One of the best explanations for what is known about transmission has been written by Erin S. Bromage, Ph.D., a comparative immunologist and associate professor of biology (specializing in immunology) at the University of Massachusetts Dartmouth.

The formula for COVID-19 being successfully transmitted to another person is related to the amount of a person's exposure to the virus, multiplied by the amount of time someone is with the infected person, he says. The more time someone spends with someone exposed, the greater the risk of becoming infected.

Bromage says the routes of transmission are known to be via a bathroom, a cough, a sneeze, and from droplets released when breathing. If a person coughs or sneezes, some of the infected droplets can hang in the air for a few minutes, filling a room with viral particles. This is why there is risk of indoor transmission. Speaking also releases some droplets, which is why remaining six feet from an infected person is important.

Somewhere in the range of 20% to 44% of people may be infected and have no symptoms or may be presymptomatic. An individual may shed virus for up to five days before developing symptoms. This is why social distancing remains important, especially indoors, he says.

The biggest known super spreading events are meat packing plants, weddings, funerals, birthday parties and business networking. Other super spreading locations include a restaurant, a call center, a choir rehearsal and an indoor sporting event.

Bromage says 90% of transmission events are home, workplace, public transport, social gatherings and restaurants. Very few outbreak events were related to shopping or from an outdoor environment. Read more of Bromage's analysis on transmission risks (updated on May 20) here.

Wastewater surveillance

Wastewater is water that returns to the public utility system after it’s been used for purposes such as flushing a toilet, bathing, washing dishes, etc. In wastewater surveillance, public health officials collect sewer system samples underneath specific buildings or water treatment plants —to test for infectious pathogens like SARS-CoV-2, hepatitis or parasites. It is also used to detect illicit drugs and changes in dietary patterns. Wastewater surveillance has been around since 1954 when epidemiologists in South Africa began using it to detect parasites contaminating local drinking water. Currently, around 58 countries use wastewater surveillance as part of public health efforts, according to the CDC.

Wastewater testing has been an important pandemic tool for tracking COVID-19 cases in addition to laboratory testing of cases because it is an early indicator of rising or falling cases. Around a third to half of people infected with SARS-CoV-2 shed the virus in feces providing a leading indicator — by about one to four days — that cases and hospitalizations are going to rise or fall. For example, the coronavirus identified in Boston’s wastewater increased before Boston’s Omicron case numbers did, and then went down before case numbers did. Missouri’s wastewater surveillance system—which includes genetic sequencing for variants—identified Delta cases last summer weeks before laboratory testing did, according to COVID-19 Data Dispatch.

In February 2022, the CDC added a wastewater tracking data system to its COVID-19 tracking dashboard. Public health officials are testing wastewater for SARS-CoV-2 in ten states, providing a snapshot of virus trends.