Coronaviruses1 are a large family of viruses that usually cause mild to moderate upper-respiratory tract illnesses, like the common cold, in people. However, three times in the 21st-century coronavirus outbreaks have emerged from animal reservoirs to cause severe disease and global transmission concerns. This post ”A Coronavirus Primer: Transmission & Vaccines” seeks to provide updated information about this disease.
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There are hundreds of coronaviruses, most of which circulate among animals including pigs, camels, bats, and cats. Sometimes those viruses jump to humans—called a spillover event—and can cause disease. Seven coronaviruses are known to cause human disease, four of which are mild: viruses 229E, OC43, NL63, and HKU1. Three of the coronaviruses can have more serious outcomes in people, and those diseases are SARS (severe acute respiratory syndrome) which emerged in late 2002 and disappeared by 2004; MERS (Middle East respiratory syndrome), which emerged in 2012 and remains in circulation in camels; and COVID-19, which emerged in December 2019 from China and a global effort is underway to contain its spread. COVID-19 is caused by the coronavirus known as SARS-CoV-2.
Thanks to research investments into the SARS and MERS outbreaks, NIAID scientists and grantees are better prepared to develop diagnostics, therapeutics, and vaccines against COVID-19. Included in those projects are basic research to understand how the virus infects cells and causes the disease; adapting platforms used to develop diagnostic tests and vaccines, and evaluating treatments such as broad-spectrum antivirals and potentially monoclonal antibodies.
In fact, within two weeks of the discovery of COVID-19, NIAID researchers had determined how the virus enters cells.
Why Are Coronaviruses a Priority for NIAID?
When SARS emerged from China in 2002 it swept across the globe—largely through air travel—causing deadly illness. More than 8,000 people fell ill and 774 died, numbers COVID-19 surpassed within two months. SARS drew the collective focus of researchers throughout the world. The disease disappeared in 2004, likely due to isolation and quarantine containment measures, and no cases of SARS have been reported since. In 2012, a new coronavirus emerged in the Middle East causing an illness similar to SARS. Again, researchers at NIAID and across the globe initiated studies to understand MERS-CoV and how to stop it. Research efforts from those two outbreaks—including the development of a DNA vaccine candidate for SARS by NIAID’s Vaccine Research Center—have prepared scientists to quickly assess the severity and transmission potential of SARS-CoV-2, and to develop countermeasures.
How Is NIAID Addressing This Critical Topic?
When MERS emerged in 2012 and COVID-19 was identified in 2020, NIAID intramural and extramural scientists mobilized quickly to study the viruses, efforts which continue today. Key areas of investigation include basic research on their origins, how they cause disease and developing animal study models, new treatments, and vaccines.
COVID-19, MERS & SARS
In January 2020 a novel coronavirus, SARS-CoV-22, was identified as the causative agent of an outbreak of viral pneumonia centered around Wuhan, Hubei, China. That disease is now called COVID-19. The virus has caused a widespread outbreak of disease similar to SARS throughout China, with exported cases occurring in four other continents, including the United States. The Centers for Disease Control and Prevention (CDC) has developed a test to diagnose COVID-19 in respiratory and serum samples from clinical specimens. NIAID also is accelerating efforts to develop additional diagnostic tests for COVID-19. These tests would help facilitate preclinical studies and aid in the development of medical countermeasures. Much of NIAID’s work on COVID-19 is an expansion of its work on the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS).
A Viral Respiratory Disease?
MERS-CoV is a viral respiratory disease that was first reported in Saudi Arabia in 2012 and has since spread to more than 27 other countries, according to the World Health Organization. Some people infected with MERS-CoV develop severe acute respiratory illness, including fever, cough, and shortness of breath. From its emergence through December 2019, WHO has confirmed 2,499 MERS cases and 861 deaths (or about 1 in 3). Among all reported cases in people, about 80% have occurred in Saudi Arabia. Only two patients in the United States have tested positive for MERS-CoV, both of whom recovered. They were healthcare providers who lived in Saudi Arabia, where they likely were infected before traveling to the U.S., according to the Centers for Disease Control and Prevention. Infection with SARS-CoV can cause a severe viral respiratory illness. SARS was first reported in Asia in February 2003, though cases subsequently were tracked to late 2002. SARS quickly spread to about two dozen countries before being contained after about four months. Since 2004, there have been no known SARS cases. Research evidence suggests that SARS-CoV-2, MERS-CoV, and the original SARS-CoV all originated in bats. SARS-CoV then spread from infected civets to people, while MERS-CoV spreads through infected dromedary camels to people. Scientists are trying to determine how SARS-CoV-2 spread to people.
Characterizing MERS-CoV Disease
Since its emergence in 20123, NIAID scientists have advanced their understating of how MERS-CoV causes disease, focusing on developing animal models of disease and countermeasures to disease. Work has shown that for MERS-CoV to infect a person, the virus enters cells using the spike, or S protein. After entering the cell, the virus delays the normal immune system response, allowing the infection to gain a foothold in the body. By the time the immune system recovers, the infection has progressed and becomes much harder to fight. Scientists also have characterized different strains of MERS-CoV and can determine through tests how those stains affect different animals and how their form—liquid or aerosol—affects their stability. A rhesus macaque model of MERS-CoV has shown that clinical signs of disease appear within 24 hours of infection, and the virus causes disease deep within the lungs, leading to pneumonia. Researchers use the rhesus and other models to study how MERS-CoV causes disease and to evaluate potential vaccines and treatments. NIAID-funded researchers also have established several small-animal models of infection in mice that have been critical in advancing the development of MERS-CoV medical countermeasures.
Tracking Coronavirus Transmission4
Coronaviruses evolve quickly and have a long history of shifting between animal species, leading scientists to explore the origin of MERS-CoV and how it infects people. While many other coronaviruses in nature are not known to infect people, SARS-CoV-2, MERS-CoV and the original SARS-CoV are notable for their ability to infect a variety of different species.Research evidence suggests that all three coronaviruses originated in bats. SARS-CoV then spread from infected civets to people, while MERS-CoV spreads through infected dromedary camels to people. Scientists are trying to determine how SARS-CoV-2 spread to people. Epidemiological studies have shown that MERS-CoV can transmit between people who are in close contact, such as family members or patients being treated in clinical settings. Outbreaks have been closely linked to hospital settings.
Developing Therapeutics and Vaccines for Coronaviruses5
NIAID-funded scientists are exploring ways to treat and prevent human coronavirus infections by working to develop new antibodies, drugs, and vaccines that block entry to cells, delay the immune system response, or block viral replication. For COVID-19, NIAID scientists, working in Bethesda, Md., and Hamilton, Mont., are preparing to test the antiviral drug remdesivir, which has shown promise against other coronaviruses in animal models. NIAID is exploring other broad-spectrum antiviral compounds for activity against COVID-19. NIAID also plans to evaluate Kaletra, also known as lopinavir and ritonavir, and interferon-beta for their activity against COVID-19. The NIAID Vaccine Research Center (VRC) is drawing on broad research experience with coronaviruses, combined with a wide network of collaborators from academia, other government agencies, and industry, on the development of a vaccine candidate expressing the viral spike protein of SARS-CoV-2 using a messenger RNA vaccine platform technology.
NIAID anticipates the experimental vaccine will be ready for clinical testing in the coming months. NIAID scientists at Rocky Mountain Laboratories are collaborating with Oxford University investigators on the development of a chimpanzee adenovirus-vectored vaccine candidate against COVID-19. In addition, NIAID-supported scientists also are working to see if vaccines developed for SARS are effective against COVID-19. Grantees studying MERS are working to develop vaccines that target the viral Spike protein of a live, attenuated MERS vaccine, which is a type of vaccine that contains a version of the living microbe that has been weakened in the lab so it cannot cause disease. Grantees and NIAID VRC investigators are using knowledge learned from SARS vaccine development to create MERS treatments.
One method for MERS uses neutralizing monoclonal antibodies—developed from a recovered MERS patient and immunized rhesus macaques—that target multiple sites on the virus S protein.NIAID has also supported the clinical testing of two promising antibody-based therapeutics, which prevent the virus from infecting and entering cells. NIAID conducted a phase 1 clinical trial of SAB-301, an experimental MERS treatment developed from cattle that make human antibodies. This was shown to be safe and well-tolerated in healthy adults. More recently, NIAID supported a Phase I clinical trial of a combination of two monoclonal antibodies, REGN3048 and REGN 3051, and demonstrated this combination was also safe and well-tolerated. Planning for follow on Phase 2/3 efficacy studies using SAB-301 is currently ongoing with partners where MERS is endemic, including the Kingdom of Saudi Arabia.
Who Provided this Info6?
The Division of Microbiology and Infectious Diseases (DMID) supports extramural research to control and prevent diseases caused by virtually all human infectious agents except HIV. DMID provides funding opportunities and a comprehensive set of resources for researchers that support basic research, preclinical development, and clinical evaluation.
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