COVID-19: A Closer Look

US Pharm. 2021;45(4):4-7.

There are many types of human coronaviruses, including some that commonly cause mild upper respiratory tract illnesses. But coronavirus disease 2019 (COVID-19) is a new disease, caused by a novel coronavirus not previously seen in humans.¹ Most people infected with COVID-19 experience a mild-to-moderate respiratory illness and recover without requiring special treatment. Older people and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious symptoms.¹

Because COVID-19 spreads primarily through droplets of saliva or discharge from the nose when an infected person coughs or sneezes, it is imperative that people practice respiratory etiquette.¹ To prevent and decrease transmission of COVID-19, people must protect themselves and others from infection by receiving COVID-19 tests, wearing masks, frequently washing their hands, using alcohol-based sanitizers, practicing social distancing, and not touching their faces.¹

The first two vaccines made available in the United States, one developed by Pfizer/BioNTech and the other by Moderna, work via a novel messenger RNA (mRNA) mechanism. In these vaccines, the mRNA carries instructions to make the severe acute respiratory syndrome coronavirus-2 spike (SARS-CoV-2) protein, the prickly projections on the surface of the virus.^1,2 The immune system builds an immune response against the protein, thereby learning how to protect against future infection. A third vaccine by Johnson & Johnson recently received an Emergency Use Authorization (EUA) from the FDA and is currently available. Unlike the Pfizer and Moderna vaccines, which store instructions on single-stranded mRNA, the Johnson & Johnson vaccine uses double-stranded DNA.

COVID-19

COVID-19 spreads primarily from close contact with a person who has COVID-19. People are typically infected from the respiratory droplets of infected people. They may also be infected by touching a surface or object that has the virus on it, and then by touching their mouth, nose, or eyes, but this is thought to be much less common than initially believed.³

The World Health Organization (WHO) believes COVID-19 originated in Wuhan—the Chinese city where the new SARS-CoV-2 virus was first identified—and expanded across China and abroad. By tracing the virus’ path, WHO is able to help prevent future viral spillovers.²

Many researchers think that COVID-19 may have originated in bats, but how it jumped to people is unknown. Other coronaviruses have passed from an intermediate animal host; for example, the virus that caused an outbreak of severe acute respiratory syndrome in 2002–2004 probably came to people from civets.²

Searching and nailing down the origins of a virus can take years, if it can be done at all, and the investigation will also have to navigate through the current highly sensitive political situation between China and the U.S. Coordination between these two countries may create a more positive environment to conduct collaborative research in this field and find the origin of the virus.⁴

COVID-19 Variants

Currently, information about the characteristics of variants of COVID-19 is rapidly emerging. Scientists are working to learn more about how easily the variants might spread, whether they can cause more severe illnesses, and whether currently authorized vaccines will protect people against them.⁵

In the United Kingdom, a new variant, called B.1.1.7, has emerged with an unusually large number of mutations. This variant spreads more easily and quickly than other variants. This variant was first detected in September 2020 and is now highly prevalent in London and southeast England. It has since been detected in numerous countries around the world, including the U.S. and Canada.⁵ A recent study suggests that this variant may be associated with an increased risk of death, but additional studies are needed to confirm this finding.⁵

In South Africa, another variant called 1.351 has emerged independently of the variant detected in the U.K. This variant, originally detected in early October 2020, shares some mutations with the variant detected in the U.K. Cases caused by this variant have been detected outside of South Africa, including in the U.S.⁵

In Brazil, a variant called P.1 has emerged; it was identified in four travelers from Brazil who were tested during routine screening at the Haneda airport outside Tokyo, Japan. This variant contains a set of additional mutations that may affect its ability to be recognized by antibodies. This variant was detected in the U.S. at the end of January 2021.⁵

How these variants are affected by existing therapies, such as vaccines and tests, is still unknown.

Vaccines: mRNA and Recombinant

In the two mRNA vaccines currently available, once the vaccine is injected in the muscle, the mRNA is taken up by the mobile white blood cells of the immune system, especially at sites of infection, and instructs those cells to make the spike protein. The spike protein then appears on the surface of these macrophages, inducing an immune response that mimics the way we fight off infections and protects us from natural infection with SARS-CoV-2. Enzymes in the body then degrade and dispose of the mRNA. In this vaccination, no live virus is involved and no genetic material enters the nucleus of the cells.^2,6

Scientists have been working on mRNA vaccines for years, but these are the first mRNA vaccines to be broadly tested and used in clinical practice. What is innovative is the breakthrough insight that put the mRNA inside a lipid coating to prevent it from being degraded by enzymes.^1,6

The two novel vaccines developed quickly to prevent COVID-19 are remarkably effective against coronavirus. In large clinical trials that enrolled tens of thousands of people, the vaccines lowered the chance of developing COVID-19 by around 95% as compared with placebo injections.^1,2 Additional details make these results even more compelling⁶:

• The vaccines prevented not only the mild form of the disease due to SARS-CoV-2 but also severe disease. Prevention of severe disease could convert COVID-19 from the global threat it is now into more of a nuisance, like the common cold

• The studies enrolled participants who were quite representative of the U.S. population—age, sex, race, and ethnicity were all broadly included

• While both vaccines are given as two doses, some protection became apparent just 10 to 14 days after the first dose

The efficacy noted after the first dose has raised questions about whether a two-dose schedule is necessary. However, the 95% vaccine efficacy results come after the second dose, which boosts the immune response, and is likely to make it more durable. For now in the U.S., the CDC and FDA recommend proceeding with the two-dose schedule whenever possible.⁶

Overall, these impressive results put the two mRNA vaccines in the company of our most effective vaccines to date. The protection is far better than anticipated, which is why many specialists in infectious diseases, virology, immunology, and public health are willing to highlight the vaccine’s efficacy.⁶

Since the vaccines were only tested in the summer of 2020, there is still no information about the period of protection. Data from the phase I trial of the Moderna vaccine suggested that neutralizing antibodies decline slightly over time. With no information available on how long the vaccines will be protective, there is currently no specific recommendation for booster doses.²

In contrast to mRNA vaccines, recombinant vaccines use a small piece of genetic material from the virus to trigger an immune response.⁷ This genetic material for COVID-19 does not replicate in the body. A specific piece of the virus can be targeted, and recombinant vaccines are common and generally safe to use in a large population of people—even those with chronic health problems or who are immunocompromised.⁸

Johnson & Johnson’s vaccine, a recombinant vaccine, has been authorized for emergency use in the U.S.⁸ It is an experimental viral vector vaccine that uses a weakened live adenovirus as the delivery method (vector) for transporting a recombinant vaccine for COVID-19.⁸ The Johnson & Johnson vaccine uses the same technology that was used to create the Ebola vaccine.⁷ The global efficacy of the Johnson & Johnson vaccine is 66% against moderate-to-severe illness, but it is 85% effective against severe disease.⁹

Vaccine Side Effects

The mRNA vaccines and the Johnson & Johnson vaccine are classified as “reactogenic”—meaning that they will cause some side effects in most people who receive them, indicative of the rapid immune response they generate. In clinical practice, both these vaccines are categorized with the same side-effect profile as the recombinant shingles vaccine (Shingrix).²

The most common side effect for all of the vaccines is pain at the injection site, especially within the 12 to 24 hours after administration. About 1% of participants in the trials categorized the pain as “severe.” Fatigue and headache are other relatively common side effects. High fevers are less common. On rare occasions, within an hour of receiving the vaccine, recipients of the Johnson & Johnson vaccine may experience an allergic reaction, resulting in difficulty breathing, swelling of the face and throat, increased heart rate, and weakness.⁸

These side effects generally resolve within a couple of days and are responsive to postvaccination acetaminophen or a nonsteroidal anti-inflammatory drug such as ibuprofen. In general, side effects are more common in younger vaccine recipients than in older ones, with the second shot inducing more side effects than the first.²

The Pfizer/BioNTech vaccine is authorized for ages 16 years and older, Moderna’s for ages 18 years and older, and Johnson & Johnson for ages 18 years and older. Aside from this age difference, there is no target population better suited to one vaccine or the other.^2,8

New Vaccines on the Horizon

Like the Johnson & Johnson vaccine, the Oxford–AstraZeneca COVID-19 vaccine uses double-stranded DNA. It is ready to complete clinical trials and request EUA from FDA. It is not yet available in the U.S.¹⁰

Novavax is developing the next generation of vaccines for serious infections. Their COVID-19 vaccine is protein-based with a vaccine efficacy of 89.3%. It can neither cause COVID-19 nor can it replicate, and it is stable at 2°-8°C. The company is planning to submit results of clinical studies to the FDA soon. Novavax is currently evaluating vaccine efficacy, safety, and immunogenicity.¹¹

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

REFERENCES

1. Patel A, Jernigan DB 2019 nCoV Response Team. Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak—United States, December 31, 2019–February 4, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:140-146.
2. Sax PE. Covid-19 vaccine—frequently asked questions. NEJM. 2021. www.nejm.org/covid-vaccine/faq. Accessed March 4, 2021.
3. CDC. How COVID-19 spreads. www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html. Accessed March 4, 2021.
4. AlTakarli NS. China’s response to the COVID-19 outbreak: a model for epidemic preparedness and management. Dubai Med J. 2020;3:44-49.
5. CDC. Science brief: emerging SARS-CoV-2 variants. Updated January 28, 2021. www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html. Accessed March 4, 2021.
6. McIntosh K, Hirsch MS, Bloom A. Coronovirus disease 2019 (Covid-19): epidemiology, virology and prevention. UpToDate, Inc. Updated February 18, 2021. www.uptodate.com. Accessed March 4, 2021.
7. Godoy M. Got questions about Johnson & Johnson’s COVID-19 vaccine? We have answers. Shots: Health News From NPR. March 4, 2021.
www.npr.org/sections/health-shots/2021/03/04/973436193/got-questions-about-johnson-johnsons-covid-19-vaccine-we-have-answers. Accessed March 6, 2021.
8. Johnson & Johnson. Press release. Johnson & Johnson COVID-19 vaccine authorized by U.S. FDA for emergency use—first single-shot vaccine in fight against global pandemic. February 27, 2021. www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial. Accessed March 4, 2021.
9. Johnson CY. Single-shot Johnson & Johnson vaccine prevents illness but shows the threat of variants. Washington Post. January 29, 2021. www.washingtonpost.com/health/2021/01/29/covid-vaccine-johnson-and-johnson/. Accessed March 6, 2021.
10. Knoll MD, Wonodi C. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet. 2021;397(10269):72-74.
11. Novavax. Press release. Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. January 28, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3. Accessed March 6, 2021.

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