Coronaviruses (abbreviated CoVs) are a family of enveloped, positive-sense single-stranded RNA viruses that infect both humans and animals. Coronaviruses got their name because their outer proteins look like a crown (corona means crown in Latin). There are four main subgroups of coronaviruses: alpha, beta, gamma, and delta.
Coronaviruses that can infect humans (called human coronaviruses) were first identified in the mid-1960s. There are seven known human coronaviruses: four common types—229E, NL63, OC43, and HKU1—and three severe types—Middle East respiratory syndrome (MERS)-CoV; severe acute respiratory syndrome (SARS)-CoV; and the 2019 novel coronavirus (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). Infection with the four common coronaviruses is common worldwide, especially in young children and during cold and flu season.
Most viruses are zoonoses, meaning they are diseases transmitted to humans from animals. These viruses have animal reservoirs, meaning that the viruses live in certain animal species without causing them harm. Passive host animals can then pass the virus along to other animals and even people, causing illness. According to the World Health Organization (WHO), bats are a common animal reservoir for multiple coronaviruses, including SARS-CoV and MERS-CoV. Bats can then infect other animals, which can go on to infect humans and make them sick. It is still unclear how SARS-CoV-2 first infected humans. Bats are a known reservoir for the virus, but the genetic differences between the virus in bats and the virus in humans are great enough to suggest that some other animal acted as an intermediary.
SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS (SARS-COV)
SARS-CoV originated in southern China in November 2002. It caused a worldwide outbreak between 2002 and 2003, resulting in 8,098 probable cases and 774 deaths (9.6% mortality). There haven’t been any SARS cases reported since 2004; SARS is considered eradicated in humans as of 2021.
SARS-CoV was transmitted from horseshoe bats to Asian palm civets, small, lean nocturnal mammals of the Viverridae family. Infected civets were being sold for meat at local markets in southern China, which is how humans became infected with SARS-CoV.
SARS-CoV is readily spread person-to-person through close contact via respiratory droplets produced when someone who is sick sneezes or coughs. SARS-CoV can also survive in urine and feces for more than 2 days at room temperature, according to the World Health Organization (WHO). Most person-to-person transmission occurred in health care settings when adequate infection control measures were not followed.
MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS (MERS-COV)
MERS-CoV, sometimes called camel flu, first emerged in Jeddah, Saudi Arabia, in 2012, and caused an outbreak localized to countries around the Arabian Peninsula. MERS infections then spread to other countries in the Middle East, followed by countries in Asia, Europe, North and South America, and Africa. MERS infections are still occurring, with new cases being confirmed by the WHO as recently as March 2021. Between 2012 and March 20, 2021, the WHO has reported 2,586 cases and 939 deaths (34.4% mortality). There were two cases of MERS reported in the United States in 2014, but none since that date.
MERS-CoV spread to humans from dromedary camels (also called Arabian camels, those with one hump on their back), which can carry the virus without getting sick. Specialists with the WHO think that bats may have transmitted the MERS virus to camels in the distant past. People who come in contact with camels that carry MERS-CoV; eat partially cooked infected camel meat; drink unpasteurized infected camel milk, or drink infected camel urine (which is considered a medicine for various illnesses in the Middle East) can get sick with MERS.
There is limited evidence of person-to-person MERS-CoV transmission, with most such transmissions occurring after close contact with severely ill people in health care or household settings. As of April 2021, the WHO considers immunocompromised people and those with diabetes, chronic lung disease, or kidney failure to be at high risk of severe disease from MERS-CoV infection.
2019 NOVEL CORONAVIRUS (SARS-COV-2) AND COVID-19
SARS-CoV-2, the newest human coronavirus, is currently causing a global pandemic of COVID-19. The virus is believed to have first emerged in Wuhan, China, though its point of origin is not a settled matter. COVID-19 was first reported in December 2019.
Most of the people initially infected were sellers at the Huanan Seafood Wholesale Market in Wuhan, China, who sold live or recently killed fish, animals, and birds. The seafood market was quickly closed for cleaning and disinfection. As of March 2021, WHO officials have yet to determine the animal that caused sickness in people.
SARS-CoV-2 is readily transmitted from person to person via respiratory droplets expressed when someone who is sick coughs, sneezes, talks, sings, and so on.
Like other respiratory illnesses, most coronaviruses are transmitted via respiratory droplets when someone coughs or sneezes.
According to a study reported in the Annals of Internal Medicine in November 2020, about a third of people with COVID-19 are asymptomatic. These people may unknowingly spread the disease due to their lack of symptoms or may spread the disease before they develop symptoms (pre-symptomatically). This finding prompted the CDC to recommend that the general public wear cloth face coverings in public where social distancing is difficult to maintain, such as grocery stores and pharmacies.
The basic reproduction number (also called R, pronounced R-nought or R-zero) of a virus is how many people on average are infected by one sick person. The higher the number, the more infectious a virus is. In general, a number greater than 1 typically means an epidemic will increase. While the basic reproduction number is constantly changing according to the latest information, the WHO estimates a preliminary R of 2.0 to 2.5 for COVID-19. This figure means that up to 2.5 people can be infected by every 1 person infected with COVID-19. For comparison, the basic reproduction number of SARS-CoV was estimated to be 2 to 3; that of common influenza strains is thought to be around 1.3; that of the measles virus, on the other hand, is estimated to be between 12 and 15.
To prevent coronavirus infection, you should follow the same preventive measures you do for other respiratory viruses like the common cold and flu, including:
- Washing your hands regularly and thoroughly with soap and water for 20 seconds
- Using an alcohol-based hand sanitizer when you cannot wash your hands (or in addition to hand washing)
- Avoiding touching your eyes, nose, and mouth
- Cleaning and disinfecting objects regularly
- Avoiding close contact with people who are sick
- Staying home if you are sick
- Getting an annual flu shot
- Receiving an FDA-approved COVID-19 vaccine
Due to the active community transmission of SARS-CoV-2 in the United States (and other countries around the world), the following precautions should also be taken to prevent the spread of SARS-CoV-2 and COVID-19.
If you are healthy and in an area of active transmission:
- Practice social distancing by minimizing contact with others and staying at least 6 feet away from others
- Avoid crowds, poorly ventilated spaces, and public places—stay home as much as possible (work and complete schoolwork at home)
- Avoid discretionary travel, shopping, and social visits
- Avoid eating in restaurants and bars—use the drive-thru, pickup, or delivery service instead
- Avoid visiting nursing homes, retirement facilities, and long-term care facilities
- Wear a cloth face mask (but be sure to properly use it by washing your hands before applying; keeping the mask over your mouth and nose while in public; never touching the front of the mask; and washing the mask after every use). As of April 2021, people must wear masks when traveling on airplanes, buses, trains, and all other forms of public transportation in the United States.
- Receive an FDA-approved COVID-19 vaccine
If you belong to the following high-risk groups:
- If you are an older person or a person with such underlying health conditions as diabetes, heart disease, asthma, or a weakened immune system, stay home and avoid other people.
- If you or anyone in your household is sick or has tested positive for COVID-19, keep the entire household at home and call your medical provider—do not go to work or school.
Anyone who has been exposed to someone known to be infected with COVID-19 should self-quarantine for 14 days, according to the CDC as of April 2021. The CDC does, however, acknowledge that some local public health authorities may permit people to end quarantine after 10 days without testing, or after day 7 with a negative test result, provided the test was administered on day 5 or later.
Animal care measures
As of April 2021, the risk of such household pets as dogs and cats spreading COVID-19 to humans is thought to be low; however, there is some evidence that humans can spread the virus to dogs and cats, with cats thought to be more susceptible than dogs. To be on the safe side, people sick with COVID-19 should be isolated from pets as well as from other family members; and pets should not be allowed to interact with anyone outside the household. Cats should be kept strictly indoors. Last, people should not put masks on their pets as masks can harm pets. Although the FDA has not issued an EUA to date for an animal COVID-19 vaccine, the Russian government announced on March 31, 2021, that it had registered the first such vaccine for animals.
State-level changes in masking mandates
Although the CDC continues to recommend the wearing of masks to slow the spread of COVID-19 (see https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover-guidance.html for the most recent guidance), 13 states have begun to lift mask mandates for the general public as of April 2021: 10 states by order of the governor (Alabama, Arkansas, Indiana, Iowa, Mississippi, Montana, New Hampshire, North Dakota, Texas and Wyoming); two by legislative action (Kansas and Utah); and one by court order (Wisconsin). Details regarding each state or territory’s mask mandate as of April 28, 2021, can be found at https://www.aarp.org/health/healthy-living/info-2020/states-mask-mandates-coronavirus.html.
A SARS-CoV vaccine was created after the 2002 SARS outbreak, but never used due to the outbreak having been controlled before the vaccine was fully developed. Vaccines are currently being developed against MERS-CoV.
As of April 2021, there are three COVID-19 vaccines licensed by the Food and Drug Administration (FDA) for use in the United States: the Pfizer-BioNTech vaccine (also called tozinameran) for persons 16 years of age or older; the Moderna vaccine (also called mRNA-1273) for persons 18 years of age and older; and the Johnson & Johnson COVID-19 vaccine (also called Ad.26.COV2.S or the Janssen COVID-19 vaccine) for persons 18 years of age and older. The first two vaccines are given as two shots 28 days apart in the muscle of the upper arm. These vaccines are mRNA vaccines (also called genetic-code vaccines), which means that they use a copy of messenger RNA to produce an immune response in the recipient; they do not use the live virus that causes COVID-19. A person is considered fully vaccinated two weeks after the second shot.
The Johnson & Johnson vaccine is a viral vector vaccine; it uses a virus that does not cause disease to carry genetic material from the disease-causing virus to stimulate an immune response. Unlike the two mRNA vaccines, the Johnson & Johnson vaccine requires only one dose. Its additional advantage is that it does not have to be shipped frozen and remains viable in a standard refrigerator for several months. Although administration of the Johnson & Johnson vaccine was briefly paused by the CDC on April 13, 2021, its administration was resumed on April 23. A person is considered fully vaccinated two weeks after the single dose of this vaccine.
According to the CDC, large-scale Phase 3 trials of the AstraZeneca COVID-19 vaccine (AZD1222) and the Novavax COVID-19 vaccine are under way in the United States as of April 2021. The AstraZeneca vaccine is a viral vector vaccine, and the Novavax vaccine, also known as NVX-CoV2373, is a protein subunit vaccine. Both vaccines require ?two doses for full effectiveness.
Other COVID-19 vaccines approved for use by other countries as of mid-April 2021:
- Viral vector vaccines. These vaccines use a chemically weakened virus to transport fragments of the disease virus to stimulate an immune response. They include Gam-COVID-Vac, developed in Russia; AD5-nCoV (Convidecea), developed by the Chinese Academy of Military Medical Sciences; and AZD1222, developed by AstraZeneca and the University of Oxford. Administration of the AstraZeneca vaccine was paused briefly in early March 2021 in Germany, France, Spain, and Italy due to fears that it might be associated with unusual blood clots in some recipients. The European Medicines Agency (EMA) advises that the vaccine’s benefits outweigh the risks, however, and administration resumed on March 18, 2021. As noted above, the AstraZeneca vaccine is presently undergoing trials in the United States for possible approval by the FDA
- Inactivated virus vaccines. These include CoronaVac and BBIBP-CorV, developed by Chinese pharmaceutical companies and government institutes; CoviVac, developed by the Russian Academy of Sciences; and BBV152 (Covaxin), developed by the Indian Council of Medical Research.
- Protein subunit vaccines. These include EpiVacCorona, developed by the Vector Institute in Russia; and RBD-Dimer (ZF2001), developed by the Chinese Academy of Sciences.
As of April 26, 2021, over 1.03 billion doses of COVID-19 vaccines had been administered worldwide, according to official national health agencies; as of the same date, the CDC reported that 230,768,454 Americans had received the first dose of an approved COVID-19 vaccine. In December 2020, when the supply of approved vaccines was limited, the CDC issued priority recommendations for the United States as follows:
- Phase 1a: health care workers and residents of long-term care facilities.
- Phase 1b: frontline essential workers (fire fighters, police officers, corrections officers, food and agricultural workers, United States Postal Service workers, manufacturing workers, grocery store workers, public transit workers, and teachers, support staff, and daycare workers) and adults over 75 years of age.
- Phase 1c: Adults between 65 and 74 years of age; people between 16 and 64 years of age with underlying health conditions; and people who work in transportation and logistics, food service, housing construction and finance, information technology, communications, energy, law, media, public safety, and public health.
The CDC updated these priority recommendations in April 2021 to state that all Americans over 16 years of age are now eligible for vaccination even though the supply of vaccines is still limited. People should contact their local health department for detailed information on vaccine administration in their area. People can also search on a website called VaccineFinder (https://vaccinefinder.org/search/) to identify locations where they can make appointments to receive a specific COVID-19 vaccine; the CDC also recommends contacting one’s local pharmacy. As of late April 2021, the federal government is working toward making all FDA-approved vaccines widely available for everyone at no cost.
The vaccines licensed for use in the United States are safe for most people. However, some persons should not receive these vaccines and certain others should consult their health care provider:
- The CDC advises that people who have had severe allergic reactions in the past to any of the ingredients in the COVID-19 vaccines should not be vaccinated. People who have had severe allergic reactions to other vaccines in the past should consult a physician before receiving the COVID-19 vaccines. As of April 2021, people who do not have a history of allergic reactions to vaccines are observed for 15 minutes after receiving the shot; people who do have such a history are observed for 30 minutes afterward. Anyone who has a severe allergic reaction to the first COVID-19 vaccine shot is advised not to receive the second shot.
- Pregnancy and lactation: Pregnant and lactating women were excluded from the COVID-19 vaccine trials, so there are few data about the safety of the vaccine in this population. The CDC, however, considers infection with COVID-19 to be a higher risk to pregnant women and their unborn children than potential risks associated with the vaccine.
- Children and younger teenagers: Children were excluded from the first COVID-19 vaccine trials. Trials of the vaccines’ safety and efficacy in children began in March 2021, with data expected to be available in early summer.
- People who have tested positive for COVID-19: Those who had symptoms of the disease should wait until they have met all criteria to discontinue isolation to receive the vaccine. People who received antibody therapy against the virus should wait 90 days before being vaccinated.
- People who are immunocompromised: Patients with HIV infection or weakened immune systems should discuss the risks and benefits of vaccination with their physician before receiving the COVID-19 vaccine. As of April 23, 2021, the CDC has posted updated information for specific groups of people at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/specific-groups.html.
Symptoms of a common coronavirus are similar to a cold or upper respiratory infection, such as:
- Stuffy nose
- Runny nose
- Sore throat
- General malaise (feeling unwell)
The more severe SARS-CoV, MERS-CoV, and SARS-CoV-2 strains can cause more severe symptoms and lower respiratory tract infections, such as pneumonia or bronchitis. More severe infections are more common in older people, infants, people with weakened immune systems, and people with underlying conditions such as heart disease.
SARS symptoms include:
- Fever and chills
- Body aches
- Other pneumonia symptoms (mucus-producing cough, shortness of breath, chest pain while coughing, nausea, vomiting, weakness)
MERS symptoms include:
- Fever and chills
- Shortness of breath
- Other pneumonia symptoms (mucus-producing cough, chest pain while coughing, nausea, vomiting, diarrhea, weakness)
COVID-19 symptoms. According to the CDC, people may have COVID-19 if they experience cough and shortness of breath or difficulty breathing, or if they have at least two of these symptoms:
- Fever and chills
- Repeated shaking with chills
- Muscle pain
- Sore throat
- New loss of the senses of taste or smell
There are two major categories of testing for COVID-19: diagnostic (to test whether a person is presently infected); and antibody testing (to detect antibodies to the virus as evidence of past infection). Diagnostic testing uses two laboratory methods: molecular (reverse transcription polymerase chain reaction or RT-PCR) testing or antigen testing. Antibody testing is done on a blood sample. Diagnostic testing requires collecting a nasal swab and/or a throat swab; sometimes a saliva sample may be collected. Antibody testing requires a blood sample drawn from a vein or collected from a fingerstick. Neither type of testing requires any preparation on the patient’s part.
Diagnostic kits for SARS-CoV-2 were made available by the CDC on February 4, 2020, to ship to qualified U.S. and international laboratories. As of April 2021, the FDA has issued EUAs for more than 80 different diagnostic tests for COVID-19. Patients must go to their physician or an authorized testing center to be tested for the virus; however, the FDA has also approved several test kits for the virus’s antigen that allow a person to collect a nasal sample at home and then send it to a certified laboratory for analysis. Some require a doctor’s prescription but at least one does not. To use these antigen tests, the user must first download the appropriate application (app) for a smartphone. In addition, the Lab Tests Online website has added a link to HealthTestingCenters.com (https://www.healthtestingcenters.com) that allows people to order (purchase) COVID-19 tests online or over the telephone.
There is currently only one FDA-approved coronavirus-specific antiviral treatment: remdesivir, for COVID-19. The treatment for most coronaviruses is similar to treatment for the common cold: rest, fluids, and over-the-counter medications for fever, sore throat, and congestion. More seriously ill patients may require hospitalization to receive medical care to help relieve their symptoms and ensure their organs are functioning properly, such as using a ventilator to assist with breathing.
There is some evidence that vitamin D deficiency increases the risk of a severe course of COVID-19 in infected persons, particularly those of Black or Asian origin. There are a number of clinical trials under way to identify any specific role for vitamin D in COVID-19 prevention and management.
There are currently no approved SARS-CoV-specific antivirals. There are also none in development because the outbreak was stopped by adequate infection control measures.
MERS-CoV-specific monoclonal antibodies created from a person who recovered from MERS are being pursued as antibody drugs.
A Phase 1 trial showed that a combination of two other monoclonal antibodies, called REGN3048 and REGN3051, were safe and well-tolerated in healthy adults.
Another Phase 1 clinical trial, conducted by the National Institute of Allergy and Infectious Disease (NIAID), showed that an experimental anti-MERS-CoV antibody, called SAB-301, was safe and well tolerated in healthy adults. According to the NIAID, a Phase 2/3 trial is currently being planned for areas where MERS-CoV is still endemic, such as Saudi Arabia.
The only drug currently approved by the Food and Drug Administration (FDA) to treat COVID-19 is remdesivir (Veklury), an antiviral agent approved by the FDA on October 22, 2020. Other currently available drugs are being repurposed to see whether they are effective against SARS-CoV-2; these include nitazoxanide, ivermectin, and niclosamide. Investigational antiviral drugs include molnupiravir and favipiravir; investigational immune modulator drugs include infliximab (Remicade), abatacept (Orencia), cenicriviroc, and tocilizumab.
On June 15, 2020, the FDA revoked the emergency use authorization (EUA) of hydroxychloroquine and chloroquine to treat COVID-19. The agency reported that “these medicines showed no benefit for decreasing the likelihood of death or speeding recovery.” On July 4, 2020, WHO discontinued its trials of hydroxychloroquine and lopinavir/ritonavir for the same reasons.
Other drugs made available to treat COVID-19 under the FDA’s Emergency Use Authorization (EUA) as of April 2021 include:
- Casirivimab/imdevimab: This treatment is a drug “cocktail” of two monoclonal antibodies. It was given an EUA on November 21, 2020, to treat nonhospitalized patients with confirmed COVID-19 experiencing mild to moderate symptoms who are at high risk of severe symptoms and hospitalization.
- Baricitinib in combination with remdesivir: Baricitinib is a kinase inhibitor used to treat rheumatoid arthritis. The FDA issued an EUA on November 19, 2020 for the use of this combination in hospitalized COVID-19 patients aged 2 years and older who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.
- Bamlanivimab plus etesevimab: Etesevimab is another monoclonal antibody. The FDA gave the combination of bamlanivimab and etesevimab an EUA on February 8, 2021, for the treatment of mild to moderate COVID-19 in adults and children 12 years and older who are at high risk of progressing to severe disease. An earlier EUA for the use of bamlanivimab alone was revoked by the FDA on April 16, 2021.
Convalescent plasma: Convalescent plasma is blood plasma taken from the blood of adults who have recovered from COVID-19; it contains antibodies to the virus. Clinical trials of convalescent plasma began in April 2020. On August 23, 2020, the FDA issued an EUA for the use of convalescent plasma in treating patients with COVID-19. As of March 19, 2021, however, the CDC states that there is not enough evidence to recommend this treatment.
Other investigational treatments for COVID-19: The search for effective treatments for the disease is complex, with several types of drug therapies (antibodies, antivirals, cell-based therapies, RNA-based treatments, and repurposed drugs) under investigation. As of late April 2021, there are at least 326 different drugs being tested worldwide as possible COVID-19 treatments, according to the Milken Institute. Readers can find the most recent updates on investigational drugs at the Milken Institute link listed under website resources below.
A SARS-CoV vaccine was developed after the 2002 SARS outbreak. However, it was never used because the outbreak was under control and the virus’ spread was halted before the vaccine was ready. It took about 20 months from when the SARS-CoV genome data was available until the vaccine was ready for human trials.
In July 2019, results from a Phase 1 clinical study showed that Inovio Pharmaceuticals and GeneOne Life Science’s DNA vaccine candidate, called GLS-5300, was safe and well-tolerated in healthy adult volunteers. More than 85% of the 75 participants showed a detectable immune response to MERS-CoV comparable to MERS survivors after two doses of the vaccine candidate.
Another Phase 1 clinical trial started in December 2019 in Saudi Arabia studying the safety of another vaccine candidate, called chimpanzee adenovirus Oxford 1 (ChAdOx1), in healthy adults. The vaccine is made from a chimpanzee virus that cannot replicate and expresses a MERS protein.
Noninjectable immunizations against COVID-19 are under development along with injectable vaccines. Although these newer types of vaccines are only in Phase 1 trials as of April 2021, candidates include two intranasal vaccines (MV-014-212 and AdCOVID); two oral vaccines (hAd5 T-cell and VXA-CoV2-1); two orally inhaled vaccines (saRNA inhaled and ChAdOx1 nCov-19); and one administered by microneedle (PittCoVacc) developed at the University of Pittsburgh.
As of April 2021, the following COVID-19 vaccines have not yet been approved for administration in any country but are in late-stage development:
- Viral vector vaccines: These include IIBR-100, developed by the Israel Institute for Biological Research; and GRAd-COV2, developed by Italy’s national institute for infectious diseases.
- Virus subunit vaccines: These include NVX-CoV2373, developed by Novavax, which uses recombinant nanoparticle technology from SARS-CoV-2 genetic sequence to generate an antigen derived from the coronavirus spike protein; and ZF 2001, developed by a Chinese biopharmaceutical company. As noted earlier, the Novavax vaccine is undergoing trials in the United States for possible authorization by the FDA.
- Genetic-code vaccines: These include CVnCoV (zoricimeran), developed by a German biopharmaceutical company; and Lunar-COV19/ARCT-021, developed by the American biotechnology company Arcturus.
- Plant-based virus-like particle vaccines: The only vaccine in this category to date is CoVLP, developed by a Canadian biotechnology company.
- Inactivated virus vaccines: These include VLA2001, developed by a biotechnology company headquartered in France.
Readers can find the most recent updates on COVID-19 vaccines at the New York Times link listed under website resources below.