Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, a new virus in humans causing respiratory illness that can be spread from person-to-person. For most people, COVID-19 resolves on its own and they won’t need medical care, recovering in less than two weeks. However, COVID-19 can cause severe illness and lasting complications, particularly among those who are at high-risk such as those immunocompromised or have underlying medical conditions.
The COVID-19 pandemic has been one of the worst public health challenges in history, resulting in the deaths of over 6.8 million people, including more than 1 million Americans, as of April 2023. SARS-COV-2 has infected more than 763 million people worldwide, leaving a significant number of survivors with lingering symptoms and leading to lockdowns which caused severe social and economic disruptions around the globe. Many COVID-19 deaths occurred prior to the FDA approval of any vaccine or treatment to help prevent and/or treat infection and protect people from severe illness and hospitalization. Vaccination and treatment programs have had challenges in reaching many people in underserved communities and many people who are hesitant have refused vaccines or had challenges getting effective treatments in a timely fashion.
COVID-19 vaccines are currently the first line of defense in protecting the population against COVID-19 and are a primary reason why most people are now able to recover from illness. The CDC recommends that everyone who is eligible should stay up to date on their COVID-19 vaccines.
Causes and Complications
COIVD-19 primarily spreads when the droplets that contain the SARS-CoV-2 virus are released by someone with COVID-19 sneezing, coughing, or talking. Infectious droplets can land in the mouths or noses of nearby people or be inhaled into their lungs and, variants since Omicron can remain in the air for hours at a time.11
Since COVID-19 is a relatively new disease, additional risk factors for severe COVID-19 may continue to be identified. In some cases, people who get COVID-19 can develop severe complications, including pneumonia, difficulty breathing or organ failure, causing a need for hospitalization and intensive care. These severe complications can often lead to death and number in the hundreds, with the CDC consistently identifying more and more.
The risk of severe disease increases steadily as people age, particularly among those over age 65.11 Additionally, those of all ages with underlying medical conditions, including but not limited to heart disease, diabetes, lung disease, or people with weakened immune systems, are at higher risk to experience COVID-19 complications.12
It is important to note that anyone can get sick with COVID-19, even healthy people, and serious problems related to COVID-19 can happen to anyone at any age, regardless of whether they had asymptomatic or symptomatic acute cases of COVID.
Prevention and Treatment
COVID-19 can be prevented, or its effects lessoned, through pharmaceutical (vaccination, anti-viral treatments) and non-pharmaceutical interventions (masking, physical distancing, hand hygiene, etc.). All of these preventative & treatment measures are important to protect individuals from acquiring and transmitting the COVID-19 virus and the CDC advises following all the latest guidance.
Most people with COVID-19 have mild illness and can let the body fight the infection on its own with rest and fluids. The symptoms can also be treated with over-the-counter medicines, such as acetaminophen or ibuprofen. However, people should be aware that they could still have serious long-term health effects from COVID, even if they experienced mild illness.
Vaccination and Treatments
COVID-19 vaccines are currently the first line of defense in protecting against COVID-19 and the CDC recommends that everyone who is eligible stays up to date on COVID-19 vaccines.
For those more likely to get seriously ill, the FDA has authorized certain antiviral medications and monoclonal antibodies that treat mild to moderate COVID-19.
The four FDA approved vaccines in the United States are listed below (as of April 2023):13
- Pfizer-BioNTech COVID-19 vaccine – An mRNA vaccine
- Moderna COVID-19 vaccine – An mRNA vaccine
- Novavax COVID-19 vaccine – A protein subunit vaccine
- Johnson & Johnson’s Janssen (J&J/Janssen) COVID-19 vaccine – A viral vector vaccine
MRNA vaccines use mRNA (messenger ribonucleic acid – a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene) created in a laboratory to direct human cells on how to make a protein that triggers an immune response and enables the body to combat COVID-19. The mRNA from the vaccines is broken down within a few days after vaccination and discarded from the body.
Protein subunit vaccines contain pieces (spike proteins) of the virus, in addition to an adjuvant. The adjuvants help stimulate the immune system in response to the spike proteins and develop a long-term memory response against them. After learning how to respond to the spike protein, the immune system will be able to respond quickly to the actual virus spike protein and protect against COVID-19.
Viral vector vaccines use a harmless, modified version of a non-COVID-19 virus, called a vector virus. The vector virus delivers important instructions to the patient’s cells on how to recognize and fight the virus that causes COVID-19.
While vaccines have been essential in combating the spread and severity of COVID-19, studies are beginning to show that vaccines are struggling to keep up with the rapidly mutating virus and effectively protect those at high-risk like the immunocompromised. During the fall and winter of 2021, Omicron, a prominent variant of COVID-19, caused a large spike in COVID-19 cases around the globe. During this time, vaccine effectiveness (VE) against COVID-19 waned for those fully vaccinated (two doses) to as low as 25% efficacy and only increased after a third dose, or booster.14 Emerging data is also raising doubts about how effective COVID-19 vaccines are in people who are at high-risk or immune-compromised with immune systems that are not fully functioning, because vaccination relies on stimulating a functioning immune system.
Antiviral treatments help to prevent severe illness and death by targeting specific parts of the virus to stop it from multiplying in the body; i.e., stopping the virus that causes COVID-19 from making copies of itself. These therapeutics are used in patients that have COVID-19 and are at high risk of becoming very sick. As of December 2022, the FDA-approved antiviral treatments available today are:15
- PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) – Oral antiviral for adults and children 12 years or older
- LAGEVRIO™ (molnupiravir) – Oral antiviral for adults
- VEKLURY® (remdesivir) – Intravenous infusion for adults and children 28 days or older
While these therapies do help to relieve symptoms of the virus and support the respiratory system, they require patients to receive a series of treatments within a specific timeframe of contracting the virus. Patients being treated with oral antivirals (Paxlovid and Lageviro) must take the treatments no later than 5 days after the first symptoms appear and are required to take the pills two times a day for 5 days. Veklury requires a prescription and patients being treated with it must receive the therapy within 7 days of symptom onset and through IV, requiring them to visit a hospital or other physical location for three consecutive days. This can be challenging, and potentially a risk to the health of vulnerable populations, such as the immune-compromised, who are at greater risk of respiratory infection, particularly the more frequently they must go to public places.
Monoclonal antibodies (mAbs) are another type of antiviral therapy composed of antibodies produced in a laboratory. mAbs work much like the natural antibodies one’s immune system makes to fight illness, but represent only one of many versions of the antibodies naturally produced by the human immune system to protect against invading pathogen. For COVID-19, mAbs are designed to bind to a single protein, or an antigen, on the virus’s surface to stop the virus from spreading further. They bind to only one antigen – the same antigen that the specific white blood cell is programed to fight (also called monovalent affinity). But mAbs designed for one strain of a highly mutating virus like COVID may not bind to proteins of other strains, which has limited their use as SARS-CoV-2 variants continue to mutate.
Monoclonal antibodies have been used to treat many diseases and illnesses beyond COVID-19, including rheumatological illnesses, organ transplant rejection, osteoporosis, infections, and cancer.
The FDA had approved the following monoclonal antibody treatments for emergency use against COVID-19, such as: 16
- Bamlanivimab plus etesevimab
- Casirivimab plus imdevimab
- Tixagevimab plus cilgavimab.
These therapies were promising and have played an important role in treating COVID-19 in earlier stages of the pandemic. However, since they were developed for specific strains or variants of COVID-19, as the virus continued to mutate, waning efficacy against new variants made it clear other approaches were needed for fighting COVID-19.
As of December 2022, the FDA has revoked their approval for bebtelovimab, the last remaining mAb authorized for treating COVID-19, as it was ineffective against the latest circulating variants of Omicron, BQ.1 and BQ1.1. This was the last of many mAbs developed and previously authorized to treat COVID which were unable to provide broad protection against SARS-CoV-2, because of how rapidly the virus mutates.
Multi-epitope binding antibodies such as SAB-185, on the other hand, has been proven to be cross-reactive to different strains (or variants) of COVID-19 in vivo in animal experiments and in clinical trials. This is where SAB has focused its efforts in developing a treatment for COVID-19.
SAB’s THERAPEUTIC PROGRAM FOR COVID-19
SAB is developing a first-in-class fully-human broadly neutralizing polyclonal antibody treatment designed to increase the body’s ability to fight variants of COVID-19, even in high-risk patients. To date, this treatment that has demonstrated efficacy against all tested SARS-CoV-2 variants.