The Science of COVID-19

Viruses are one of four major groups of microbes, in addition to bacteria, archaea, and protists. More than 5,000 viruses have been described, though there are millions of viral strains still to be discovered.

Viruses are by far the smallest microbes. They consist mostly of genetic material—DNA or RNA—which may occur in a single or double strand, depending on the species. Viruses are not cells, however, and cannot carry out life functions on their own.

Instead, they live inside other species, using host cells to grow and produce new viral particles. As they take over genetic material to reproduce themselves, the host cells often die.

Viruses are found in all groups of living things, from bacteria and fungi to plants and animals. Some viruses pose no threat to our health because the cells they attack are not human. These viruses live within other animals and plants, and even one-celled organisms like the bacteria E. coli.

But hundreds of known viruses can cause many kinds of infections, including the flu, yellow fever, rabies, polio, mumps, measles, smallpox, Ebola, AIDS, and COVID-19.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which causes COVID-19, is part of a large family of coronaviruses. These viruses are named for the “crown” of spikes on the virus particle’s spherical surface, which help the virus attach to cells and infect them.

Coronaviruses are found in humans and in other animal species, including bats, cats, and livestock. Some coronaviruses found in animals can evolve and infect people. Diseases that can be transmitted from animals to people, including diseases that are transmitted by viruses, are called zoonotic diseases.

Common coronaviruses can cause mild illness, but other coronaviruses—including MERS-CoV, which causes Middle East Respiratory Syndrome (MERS), SARS-CoV, which causes Severe Acute Respiratory Syndrome (SARS), and the novel coronavirus SARS-CoV-2—can be fatal.

There are several theories about the origin of SARS-CoV-2. It may have originated in pangolins or in bats, as did MERS-CoV and SARS-CoV.

There are more than 1,400 species of bats, and they host a variety of viruses, though not more, on a per-species basis, than other species of mammals or birds. When scientists sequenced and analyzed the SARS-CoV-2 genome—the unique genetic code of this virus—they found that this virus is most closely related to a virus that was circulating in intermediate horseshoe bats (R. affinis) in 2013. But the analysis also revealed that this strain of the virus split from the bat virus 40 to 70 years ago. It has since evolved properties that have made it particularly infectious to humans. 

Most likely, the SARS-CoV-2 virus had another mammalian host before jumping to humans. For SARS, the intermediate hosts between bats and humans were probably raccoon dogs or civets, small nocturnal mammals. For MERS, the intermediate hosts were camels.

The World Health Organization (W.H.O.) conducted an investigation into the origins of COVID-19 in early 2021 in Wuhan, the city in China where the SARS-CoV-2 virus was initially identified.

The international team included researchers who had previously helped to identify intermediary mammalian hosts—camels and bats, respectively—of MERS and Ebola outbreaks, as well as a food-safety researcher who studies how disease spreads in food markets. 

Their report, published on March 30, 2021, was inconclusive, assessing the likelihood of the possible pathways as follows:

• direct zoonotic spillover: possible to likely
• introduction through an intermediate host: likely to very likely
• through the food chain: possible
• through a laboratory incident: extremely unlikely

W.H.O. Director-General Tedros Adhanom Ghebreyesus called for further studies, noting that “as far as W.H.O. is concerned, all hypotheses remain on the table.”

Yes. Viruses can evolve rapidly and can adapt to changing conditions in ways that improve their chances of surviving and replicating. Viruses evolve through a process of natural selection, just like biological organisms.

The pace of viral evolution varies based on how the virus replicates itself and how frequently changes, also called mutations, pop up in its genetic code. To replicate, viruses need hosts. As more people become infected with SARS-CoV-2, the virus has more opportunities to replicate and more opportunities to change and adapt. 

Scientists are tracking the SARS-CoV-2 virus around the world, sequencing its genome, and sharing information about how it is changing. So far, one of the ways it has mutated is by shedding parts of its genetic code, producing new strains that have been observed in different countries. Researchers are also investigating whether humans introduced the SARS-CoV-2 virus to farmed minks in the Netherlands, and whether a strain of the virus has evolved to jump back from minks to humans.

As the virus replicates, scientists are analyzing strains for mutations that may make the virus more contagious or more severe. For example, the Delta variant, originally identified in India in December 2020, is estimated to be up to 50% more contagious than the original form of the virus and fueled surges worldwide. The Omicron variant and some of its sublineages are even more transmissible than Delta.

Even if a variant does not cause more severe illness, a more infectious virus carries significant risk of increasing the number of infected people, and so increasing the number of serious and fatal cases and further depleting healthcare resources.

Where any particular virus can live depends on its biological requirements.

Some viruses are limited to the habitat of the animals that carry them for part of their life cycle. Some have evolved to survive in more than one habitat: different flu viruses can survive in humans, birds, and other animals—and can even withstand drying out on an exposed surface.

Others are far more specialized and can survive in only one type of environment. For example, HIV (human immunodeficiency virus) cannot exist for long outside the human body.

Although coronaviruses typically do not survive long on surfaces, scientists are still learning about where the SARS-CoV-2 virus lives and how long it can persist outside the body. 

Viruses can spread in a number of different ways. Some spend part of their lives in other animals before evolving and moving to humans. Some flu viruses live first in birds and pigs before they infect people. Other viruses, like the fatal respiratory illness called the hantavirus, are carried by rodents and can infect people who breathe in dust particles from droppings. 

Since COVID-19 is caused by a new coronavirus, SARS-CoV-2, there’s still much to learn about how it spreads, and some initial ideas have already been revised.

For example, at the onset of the pandemic, it was thought that the SARS-CoV-2 virus spread through surfaces, but that is no longer considered a common way people become infected. The virus travels in respiratory droplets, which scatter when a person with COVID-19 expels air, whether by sneezing, coughing, breathing, talking, singing, or laughing. Sometimes respiratory droplets can land on surfaces, but this is not thought to be the main way by which the virus spreads.

Infection is now thought to happen mostly during close contact between people, when someone in close proximity to a person infected with COVID-19 breathes in droplets carrying the virus through their nose or mouth. Sometimes, in enclosed spaces without sufficient ventilation, these droplets can linger in the air, resulting in airborne transmission even when the infected person is not close by.

Wearing masks that cover the nose and mouth can help prevent transmission by reducing the scatter of respiratory droplets from infected people, who may or may not be showing any symptoms of illness, and by reducing the inhalation of droplets by others.

Viruses can be detected in several different ways.

Rapid COVID-19 tests detect the presence of proteins that reside on the surface of the virus. They can be easily administered at home, but they only detect the virus at certain levels because the virus’s genome can be present in the human body without making proteins. 

More precise methods of detection involve determining whether or not the genome of the virus is present. Diagnostic testing with PCR (polymerase chain reaction) allows scientists to look for direct evidence of the COVID-19 genome in a blood or tissue sample. This technique singles out the virus’s DNA and amplifies it, helping to detect its presence.

Neither the PCR test nor the rapid test can tell us what strain is present (Delta, Omicron BA.2, etc.). This requires DNA sequencing to identify the genetic markers of a specific strain.

Other tests use indirect evidence by checking for the presence of immune-system molecules called antibodies, which are produced in the blood when a person is exposed to an infectious microbe. In the test, blood samples from people with antibodies will show a reaction to the virus, confirming exposure. If no antibodies are present, there will be no reaction, indicating no exposure.

An outbreak of a disease occurs when more people than usual become ill in a particular place and time. It may be thousands of people, as happened in many cities when influenza struck in 1918.

An outbreak becomes an epidemic when an infectious disease spreads beyond a local population, lasting longer and reaching people in a wider geographical area. A pandemic is an epidemic that has spread to many regions of the world at the same time. The 1918 flu caused the deadliest pandemic of the 20th century, infecting up to one-third of the world's population at the time. Whether an outbreak can explode into an epidemic or pandemic depends on how easily a microbe can move from person to person and on individual human behavior.

The behavior of societies worldwide is equally important. On the global level, different populations make contact through travel, trade, and war, providing opportunities for microbes to reach new areas. Densely populated cities also allow microbes to spread through large groups of people. Different societies also respond differently to following safety measures that can slow the rate of infection, including, in the case of COVID-19, mask wearing, hand washing, social distancing, and, where available, getting vaccinated.

SARS-CoV-2 was first identified in December 2019 in Wuhan, China, the capital and largest city of Hubei Province, with a population of more than 11 million people. COVID-19 was declared a global pandemic on March 11, 2020.

The epidemic curve is a chart that traces the scale and pace of infections.

By tracking the onset of illness over time, the curve can help public health officials infer how a disease is spreading, make informed decisions about containment, and anticipate the need for medical care.

“Flattening” the curve refers to slowing the rate of infection to avoid overwhelming the health care system. The same number of cases spread over a longer period of time can be managed more effectively and without exhausting health resources, including hospital capacity, medical staff capacity, and equipment such as ventilators. 

Animation courtesy of RCraig09/Wikimedia Commons

Since COVID-19 is caused by a virus that is new to humans, there is no herd immunity to slow its spread.

Herd immunity occurs when community immunity is so high, the infection hits dead ends. With person-to-person spread greatly diminished, even vulnerable individuals without immunity—newborns or those who cannot be safely vaccinated—gain a degree of protection. Without herd immunity, the rate of infection is greater and faster.

In addition, COVID-19 appears to have a lot of carriers: people who show no symptoms but are contagious and unknowingly spread the virus to others.

During the time it took to identify the virus, recognize some of the means of transmission, and develop testing, SARS-CoV-2 got a head start. Thanks to international air travel, the virus was also able to quickly jump from country to country, sparking a pandemic. Misinformation, lack of rapid screening, testing, and tracing, and slow and inconsistent adoption of protective measures such as mask wearing and social distancing have fueled outbreaks around the world.

Herd immunity is reached when a significant proportion of a population is immune to an infectious disease after developing antibodies, either through illness or vaccination.

The specific percentage of a population that needs to have antibodies to reach herd immunity varies: for example, for polio, it is 80%, but for measles, it's 95%. Scientists are still determining the level for COVID-19 herd immunity, but it is expected to be above 60%, and some estimate it may be above 80%. 

Reaching herd immunity naturally, through illness alone, has significant risks and societal costs. These include deaths due to illness, long-term complications for people who have non-fatal cases of the disease, and overwhelming the health care system.

For the COVID-19 pandemic, the costs of reaching herd immunity through illness are very high. At infection and fatality rates of spring 2020, it would have meant more than 2 million deaths in the U.S. alone. The safest way to reach herd immunity to COVID-19 is through vaccination. 

As of mid-May 2022, more than 519 million people worldwide had been infected, and more than 6.2 million had died, including more than 997,000 in the U.S.

For the most recent statistics on COVID-19 cases and deaths, visit the United States Centers for Disease Control and Prevention or see global trends.

Health and health care are closely connected to social and economic conditions: where we live, where we work, how often we see a doctor, and how we are treated when we seek medical care. Public health emergencies like the COVID-19 pandemic expose existing inequalities in stark ways.

As early as April 2020, studies of hospitalization rates in the U.S. showed that Black and Hispanic communities in the U.S. were particularly hard hit by severe illness and experienced more deaths from COVID-19 than other groups. Native Americans have also been disproportionately affected.

Why? Black and Hispanic Americans and Native Americans tend to have more chronic health conditions and less access to medical care. At the same time, minority groups are more likely than whites to be exposed: Black and Hispanic Americans are overrepresented in jobs with more risk of infection, including nursing and jobs in the service industry, and are more likely to work in essential industries, which continue functioning during the outbreak. And due to entrenched residential segregation, racial and ethnic minorities may be more likely to live in densely populated areas, where preventative measures like social distancing are harder to practice.

Vaccines prompt organisms to develop immunity to a disease by triggering an immune response, which produces antibodies that recognize and respond to a specific infection. That prepares the immune system to attack the infection when it’s next encountered.

Some vaccines work by introducing a weakened virus into the body to activate an immune response without experiencing severe illness. Such “live” vaccines include measles, mumps, smallpox, chickenpox, and some versions of flu, shingles, and typhoid. 

Other vaccines, such as the flu, rabies, and tetanus vaccines, introduce “dead” or inactivated virus, which can’t replicate. Some of the COVID-19 vaccines in development are testing the use of an inactivated version of the SARS-CoV-2 virus. 

The two COVID-19 vaccines that were approved for emergency use in the U.S. in December 2020—along with several others still in development—use a different approach. Rather than introducing a live or inactive form of the whole virus into the body, these new types of vaccines spark an immune response by training our cells to make a small part of the SARS-CoV-2 virus—the spike proteins that stud its surface and make up its crown—to trigger the production of antibodies.

The two COVID-19 vaccines approved for emergency use in the U.S. in December 2020–the Pfizer-BioNTech and Moderna vaccines–use a cutting-edge new vaccine mechanism. These vaccines package genetic material, called messenger RNA (mRNA), which carries instructions for part of the virus—the protein that's responsible for the spikes on its surface, which the virus uses to attach to and infect cells.

Once a person receives the vaccine, the mRNA activates their cells to start making partial versions of the spike protein. On their own, these partial proteins aren’t harmful to most people, though they may cause a fever or aches.

But as a foreign particle, the proteins trigger the body’s immune system to produce antibodies and to train other immune cells to seek out and destroy any spike protein-carrying cells, creating a defense against a future infection by the actual SARS-CoV-2 virus.

Once it delivers its protein-making code to the vaccinated cell, the mRNA is cleared by the cell without entering its nucleus, so it does not affect the human genome.

A third vaccine approved for emergency use in the U.S. in February 2021—the Johnson & Johnson vaccine—also delivers genetic instructions for the spike protein. But it uses a different method.

Rather than mRNA, the gene is contained in DNA, which in turn is packaged into a second, harmless virus—one that is effective at broaching cells but doesn’t cause illness and has been modified so that it can’t replicate. This virus, called an adenovirus, delivers the DNA with instructions for the spike protein to a cell’s nucleus. There, the cell’s own mRNA copies the directions, activating the cell to begin producing its own spike proteins and sparking the immune reaction.   

There are several steps to producing a vaccine. First, researchers test different vaccine mechanisms in the laboratory. A promising candidate vaccine is tested in animals to determine whether it is safe to test in people. If so, it is evaluated for safety and efficacy over three phases of clinical trials with greater numbers of volunteers, including in placebo-controlled trials where some of the volunteers receive an inactive treatment. Side effects are documented, and recommendations for dosage are developed. 

All of the COVID-19 vaccines approved for use completed the clinical trials and were judged to be effective and safe. More than 40,000 people took part in the Pfizer-BioNTech vaccine trials, while more than 30,000 people participated in the Moderna vaccine trials. The Johnson & Johnson vaccine trials included more than 40,000 participants.

Once a vaccine is approved for production, manufacturing can begin under close monitoring and testing to ensure each batch is safe, uncontaminated, and potent. After approval, researchers continue to track side effects and observe any long-term effects in a population.

For example, use of the Johnson & Johnson vaccine was paused for 10 days in April 2021 on reports of potentially deadly blood clots in women under 50. In July 2021, the FDA also issued a warning about another possible side effect, Guillain-Barre syndrome, an immune system disorder that can cause muscle weakness and occasionally paralysis. In both cases, federal health officials decided the level of risk was consistent with that of other drugs and medical therapies—and less than the risk of COVID-19 infection—and could be handled with warnings to doctors. 

Courtesy of CDC

Initially, experts anticipated that it would take at least a year to develop a vaccine for SARS-CoV-2, test it for safety, and begin to produce it on a scale needed to address the global pandemic.

But the pace surpassed all expectations. By late 2020, two vaccines were approved for emergency use in the United States, and several other vaccines were in early use in other countries.

Why has the timeline been so much faster than expected? Perhaps most importantly, scientists weren’t starting from scratch. They were able to draw on work that had already been done to investigate and develop vaccines for other viruses, including for two closely related coronaviruses, SARS-CoV and MERS. For example, the SARS-CoV-2 spike protein that is a target of several of the vaccines was quickly identified for vaccine development thanks to earlier research. The adenovirus used in the Johnson & Johnson vaccine had been previously tested as a delivery mechanism in vaccines for Ebola and Zika viruses.

Another reason for the rapid vaccine development was the way in which clinical trials were conducted. Clinical trial phases, which usually take place in sequence, were allowed to run in parallel, or to overlap, to speed up testing given the urgency of the pandemic.

In addition, funding, which is sometimes difficult to secure, was made available to prevent any unnecessary delays. Regulatory approvals were also expedited, resulting in emergency authorizations for two vaccines for use in the U.S. in late 2020 and an additional vaccine in early 2021.

Vaccination for COVID-19 began in the U.S. in December 2020, with healthcare workers given top priority because of their critical role in controlling the pandemic and their risk of exposure. As additional doses of the COVID-19 vaccines became available, public health officials updated recommendations about vaccine allocation based on various groups’ risks of infection and severe illness.

On August 23, 2021, the FDA gave full approval to the Pfizer-BioNTech COVID-19 Vaccine, now known as Comirnaty (koe-mir’-na-tee), for individuals 16 years of age and older. The vaccine also continues to be available under emergency use authorization, including, as of November 2021, for individuals ages 5 to 11.

On January 31, 2022, the FDA gave full approval to the Moderna COVID-19 Vaccine, which will now be marketed as Spikevax, for individuals 18 years of age and older. A booster or third dose of the Moderna vaccine is still available under emergency use authorization.

On May 17, 2022, the FDA amended the emergency use authorization for the Pfizer-BioNTech vaccine to allow a single booster dose for children ages 5–11 at least five months after a Pfizer-BioNTech primary series. 

On June 17, 2022, the FDA authorized emergency use of the Pfizer-BioNTech vaccine in children 6 months through 4 years of age and emergency use of the Moderna vaccine for individuals 6 months through 17 years of age.

On July 13, 2022, the FDA authorized emergency use of the Novavax COVID-19 vaccine, Adjuvanted, for individuals 18 years of age and older. 

As of June 16, 2022, more than 592 million doses of the COVID-19 vaccines had been administered in the U.S., and 78.1% of the population was fully vaccinated. Vaccination rates vary widely by state and age group. The proportion of vaccinated individuals is highest among people ages 65 years and up; as of June 16, 2022, 91.3% were fully vaccinated with 69.9% of them having received one booster and 31.8%, a second booster.

Vaccination is urgently needed to slow down the spread of the infection. When person-to-person spread decreases, even vulnerable individuals without immunity—including newborns—gain a degree of protection.

Vaccination also protects against severe illness and death, and, in some cases, against reinfection and against some new variants of the virus.

Rolling out a safe and effective vaccine is just the first step. Delivering the vaccine on a scale that helps achieve herd immunity is what counts. Public confidence in the safety and efficacy of vaccination and participation in vaccination programs are critically important.

Take the vaccination campaigns against the polio virus. Outbreaks in the U.S. in the 1940s led to the development of an injectable vaccine in 1955, with an oral vaccine developed in 1961. Mass vaccination programs—boosted by a publicity campaign featuring Elvis receiving an injection—helped eliminate polio in the U.S. by 1980 and, by 1994, in the Americas.

But in parts of the world where vaccination is irregular or faces resistance, the virus persists. In Pakistan, for example, suspicion and fear of vaccination programs have led to general reluctance to vaccinate, fueling ongoing outbreaks of polio.

The most immediate goal is to control the COVID-19 pandemic by reducing the rate of infection, the rate of disease, and the rate of death due to COVID-19. This requires widespread testing and tracing to interrupt transmission by isolating the infected, effective and widespread vaccination, and treatments to reduce illness and death.

Vaccinating a large proportion of the population is critical to slowing down the spread of infection and protecting vulnerable individuals.

Once an infectious disease is under control, there is the possibility of elimination—removing the disease from a particular geographic area. Several countries, including China, Hong Kong, Taiwan, South Korea, Vietnam, Australia, and New Zealand initially focused on eliminating COVID-19 with some early, albeit temporary, successes.

Permanent removal from nature, known as eradication, is much more difficult to achieve. Only one human disease—smallpox, caused by the virus Variola—has been successfully eradicated following a massive global vaccination program in the 20th century, nearly 200 years after the development of the first vaccine in 1796.

For some viral diseases, like influenza, eradication is impossible. There are so many strains of influenza virus that they mutate frequently, so new vaccines must be constantly developed. Also, some animals can become infected with different flu strains, which can spread to people and other animals. Unless all of those animals can be inoculated, stopping transmission is not possible.

Even for diseases that can be eradicated, efforts often fall short. Measles fits the criteria for eradication: it’s easily diagnosed, there’s an effective vaccine, and the virus does not live in any other animals, so if we remove it from humans, it’s gone for good.

But measles persists—even though it can be deadly and is one of the most highly contagious diseases known. It’s not perceived as a grave threat, so there is no political or economic support for eradication. And opposition to vaccination by some has even led to a recent rise in measles cases in the United States. 

As for SARS-CoV-2, as of June 23, 2022, with 12.01 billion doses administered globally, 66.3% of the world population had received at least one dose of a COVID-19 vaccine, and only 17.8% of people in low-income countries had received at least one dose. The level of vaccine distribution is unlikely to improve in the short term, especially in settings with a weak healthcare infrastructure. As a result, some experts doubt herd immunity is possible, let alone eradication.