Novel Coronaviruses including COVID-19
Mutations, Variants, and Vaccines

LEARNING OUTCOME AND OBJECTIVES:  Upon completion of this course, you will be able to demonstrate knowledge of the pathophysiology of novel coronaviruses and the impact of such viruses on health. Specific learning objectives to address potential knowledge gaps include:

• Explain the etiology of novel coronaviruses.
• Describe the pathophysiology of novel coronaviruses.
• Discuss coronavirus mutations.
• Identify the types of vaccines used in the prevention of novel viruses.

NOVEL CORONAVIRUSES AND THEIR ETIOLOGY

It is imperative that healthcare professionals understand novel coronaviruses, how they impact humans, and what can be done to prevent spread and adverse impact.

Definitions

The word novel comes from the Latin word novus, which means “new.” In healthcare, novel typically refers to a virus or bacteria that has not been previously known (BRG, 2020).

Novel pathogens can cause both epidemics and pandemics. An outbreak of disease is designated an epidemic when there is a sudden increase in the number of cases of the disease occurring over a wide geographic area and affecting a high proportion of the population. When that disease spreads across several countries and affects large numbers of people around the world, it is then referred to as a pandemic (CDC, 2020a).

SARS-CoV-2 and Other Novel Viruses

Viruses are named according to their genetic structure for the purpose of developing diagnostic tests, vaccines, and medicines. The diseases caused by these pathogens are named in order to facilitate discussion on disease prevention, spread, transmission, severity, and treatment (WHO, 2021b).

Coronaviruses are a family of viruses named for crown-like spikes on their surface. These viruses can cause illnesses ranging from a mild common cold to serious, even fatal diseases. There are literally hundreds of different coronaviruses, and most of these viruses are found in animals. Although coronaviruses can be transmitted from animals to people, it is not a common event. It is even more uncommon for an animal coronavirus to infect people and then spread from person to person. When viruses are transmitted from animals to humans, they generally cause illnesses that affect the upper respiratory tract with varying degrees of severity (BRG, 2020; Billingsley, 2020).

The first human coronaviruses were identified in the mid-1960s. Seven of these viruses are known to affect humans today. This includes SARS-CoV-2, which is the coronavirus that causes COVID-19. Four of the seven human coronaviruses typically cause mild to moderate illness and are responsible for 10% to 30% of upper respiratory tract infections in adults. However, the other three viruses, including SARS-CoV-2, can lead to more serious infections (Billingsley, 2020).

SARS-CoV-2 is the first novel coronavirus to cause a pandemic in the last 100 years. Other pandemics were caused by novel influenza A viruses, not coronaviruses (Billingsley, 2020). COVID-19 has claimed millions of lives throughout the world and is among the most serious pandemics recorded.

There are two other novel coronaviruses that have caused severe illness:

• SARS-CoV is the virus that causes severe acute respiratory syndrome (SARS). This disease was first reported in Asia in 2003. The disease rapidly spread to 26 countries before being contained. Containment took about four months. There have not been any cases of SARS reported since 2004.
• MERS-CoV is the virus that causes Middle East respiratory syndrome (MERS). It first emerged in Saudi Arabia in 2012. The disease spread to 27 countries. An estimated 80% of reported cases of MERS were found in Saudi Arabia. In the United States, only two people tested positive and both recovered.
  (Billingsley, 2020)

Etiology of SARS-CoV-2

Determining the source of a viral outbreak is typically a complex process. In the case of the virus that causes COVID-19, epidemiologists performed field investigations to determine how this novel virus began. Surveys were conducted in the community and healthcare facilities. Nasal and throat specimens were collected for lab analyses. Survey results showed who was infected, when illness developed, and where they were just prior to becoming ill.

After analyzing the data, epidemiologists determined that the COVID-19 virus possibly came from an animal sold at a market, although its origin remains uncertain. The disease began to spread in Wuhan, China, where it became an epidemic. It then spread rapidly across the world, affecting millions of people (CDC, 2020a).

PATHOPHYSIOLOGY OF CORONAVIRUSES

Coronaviruses are enveloped, positive-stranded RNA viruses. These viruses infect many animals, and their human adaptations are probably introduced through zoonotic transmission from animal reservoirs (CDC, 2020a).

How Pathogens Cause Disease

Pathogen infection does not always cause disease. Infection occurs when pathogens such as viruses multiply inside the body. Disease occurs when the infection damages the cells of the body, resulting in signs and symptoms of illness. Whether or not disease develops depends on the specific pathogen and how susceptible a person is to that pathogen.

Novel viruses cause illness by destroying cells or by interfering with cell functioning. The body responds to viral infection with fever (heat inactivates many viruses), the secretion of interferon (which prevents viruses from reproducing), or by using the immune system’s antibodies to target the virus (NAS, 2021).

Immune Response

When viruses laden with antigens infect a human or an animal, the body recognizes them as foreign substances and reacts in what is called an immune response. This response creates antibodies against the foreign substance and is referred to as active immunity. After recovery from the infection, the human or animal is usually immune to getting the same viral disease for varying periods of time and, in some instances, perhaps a lifetime (CDC, 2020a).

Passive immunity occurs when a person is given antibodies to a disease rather than producing them through the immune system. Passive immunity can be obtained by receiving antibody-containing blood products such as immune globulin when immediate protection is required. Such protection lasts only for a few weeks or months (CDC, 2020a, 2020b).

Clinical Manifestations

Human coronaviruses typically cause mild to moderate upper respiratory tract illnesses. These types of illnesses usually last for brief periods of time. However, several human coronaviruses can cause severe symptoms and illness, such as pneumonia or bronchitis. Severe illness is more common in older adults, infants, and in people with other chronic illnesses, cardiopulmonary disease, and weakened immune systems (AL DPH, 2020).

Below are the clinical manifestations of three coronaviruses that have been or are currently responsible for pandemics:

• MERS-CoV (MERS): MERS typically affects the lower respiratory system and often causes severe symptoms including fever, cough, and shortness of breath, which often progresses to pneumonia. An estimated 3 or 4 out of every 10 patients with MERS have died. MERS continues to occur, most often appearing on the Arabian Peninsula.
• SARS-CoV (SARS): SARS symptoms usually include fever, chills, and body aches, eventually progressing to pneumonia. No human cases of SARS have been reported anywhere in the world since 2004.
• SARS-CoV-2 (COVID-19): There are multiple symptoms of COVID-19, ranging from mild to severe, which can lead to fatal illnesses such as pneumonia or sepsis. Symptoms vary considerably from patient to patient. Relatively common symptoms include, but are not limited to, fever, chills, shortness of breath, difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.
  (AL DPH, 2020; CDC, 2021c; WHO, n.d.)

Transmission of SARS-CoV-2

Human coronaviruses typically spread via close contact from person to person. Investigation shows that SARS-CoV-2 is easily transmitted from person to person and spreads primarily by:

• Coming in close contact with infected people, typically within three feet (one meter)
• Coming in contact with aerosols or droplets that contain the virus, facilitating the entry of the virus via inhalation or by direct contact with the eyes, nose, or mouth
• Being in poorly ventilated and/or crowded indoor settings where people spend long periods of time (because aerosols remain in the air or travel farther than three feet)
• Touching surfaces that have been contaminated by the virus and then touching eyes, nose, or mouth without cleaning the hands
  (CDC, 2021a; WHO, 2021a; WHO, 2020; WHO, n.d.)

Regardless of whether or not they have symptoms, persons infected with the SARS-CoV-2 virus can be contagious and spread the virus to other people. Laboratory data suggest that infected people are most infectious just before they develop symptoms (about two days before symptoms appear) and early in their illness. People with severe disease can be infectious for longer periods of time (WHO, 2021a, 2021c).

Research is ongoing to better identify how the virus is spread, which settings have the most risk of spreading the disease, and why this is so. Research is also being conducted to study emerging virus variants and why some are transmitted more easily (WHO, 2021a). To date, it is estimated than on average one infected person will infect between two and three others (BRG, 2020).

At the community level, disease risk of transmission can be hard to determine. Until there is a more precise measure of disease burden, it should be assumed that some community transmission is occurring (CDC, 2021b).

Replication

Viruses depend on their host cell’s protein pathways to reproduce or replicate. Replication can be quite different between different species and types of viruses. Generally, a virus requires attachment, penetration, uncoating and replication, assembly, and virion release (Ryding, 2021).

• Attachment occurs when the viral proteins bind to the host cell’s surface. When this takes place, viral proteins interact with receptors specific to them as well as the host cells.
• After attachment takes place, viruses penetrate the cell according to the changes that occur after binding. Such changes lead to the fusing of the viral and cellular membranes.
• After successful penetration the next step is uncoating. Uncoating involves the degradation of the viral capsid (protein cage), which releases the genomic information that facilitates the beginning of replication via transcription of viral genomic information. The remainder of the replication step is the synthesis of viral genome and proteins.
• During assembly (also referred to as maturation) the products of replication can be modified. Viral proteins and viral genome are packed into new virions (active, infectious part of the virus) that can be released from the host cell.
• Virion release from the host cell can occur in two ways. One is the lysis method, which causes the death of the host cell and allows for the release of the virion. Viruses that release in this way are called cytolytic viruses. The second method is budding. These types of viruses (called cytopathic viruses) have envelopes and do not typically kill the host cell. Instead, budding allows viruses to acquire a viral phospholipid envelope that facilitates virion release.

VIRUS MUTATIONS AND VARIANTS

When a virus’s structure changes as it replicates, such changes are referred to as mutations, and a virus with one or more new mutations is referred to as a variant (WHO, 2021c).

Viral mutation is the alteration of the sequence of a virus’s genetic code. Viral mutation is a normal physiologic occurrence, and viruses are constantly mutating. Where mutations are located in a virus’s genetic material determine how they alter a virus’s properties. For instance, a mutation may alter a virus so that it spreads more or less easily or so that it causes more or less severe disease (WHO, 2021c).

The majority of the time mutations are so small that they do not significantly affect how the virus behaves (Cleveland Clinic, 2021).

Antigenic Drift

One way that viruses can mutate is via antigenic drift. Antigenic drift refers to small changes in the genes of viruses that happen on a continual basis over time as the virus replicates. These genetic changes typically produce viruses that are closely related to each other. These viruses usually share the same antigenic properties. Thus, an immune system exposed to a similar virus will usually recognize and respond to it (CDC, 2019).

However, these small genetic changes accumulate over time and eventually cause the development of viruses that are antigenically different. When this occurs, the body’s immune system may not recognize such viruses, and illness can occur.

Antigenic viral changes are anticipated, so the composition of any vaccine must be evaluated regularly and updated as needed. Pandemics are less likely to occur with antigen drift thanks to researchers who continually monitor virus evolution and update vaccines as needed and to the gradual nature of virus replication (CDC, 2019).

Antigenic Shift

Antigenic shift is an abrupt, major change in a virus that causes the production of new proteins in the viruses that infect humans. It is typically unexpected and unpredictable. Antigenic shift leads to a new virus subtype or one that has emerged from an animal population that is so different from the same subtype of viruses in humans that most people do not have immunity to the new type of virus. When this type of shift occurs, the new viruses infect people, spread rapidly, and can lead to a pandemic (CDC, 2019).

Variants of the COVID-19 Virus

There are multiple variants of the SARS-CoV-2 coronavirus that are different from the version first detected in China. For instance, a mutation that appeared in southeastern England in September 2020 rapidly became the most common variant of the coronavirus in the United Kingdom and has been estimated as >50% more contagious than earlier viral variants (Cleveland Clinic, 2021).

Some of the SARS-CoV-2 variants identified include:

• B.1.351 (beta): This variant was identified in South Africa. It has not been known to cause more severe illnesses than earlier versions of the virus.
• B.1.1.7 (alpha): This variant was identified in England. Preliminary data suggested that this variant is more contagious than earlier versions of the virus. There have been surges of cases in locations where this new strain appeared. This variant appears to bind more tightly to the cells of the body, and it consists of 17 genetic changes from the original virus (Johns Hopkins Medicine, 2021).
• B.1.617.2 (delta): This variant was identified in India; it has two mutations in the spike protein of the coronavirus that facilitates its attachment to cells (Ellis, 2021).

Other early variants emerged in Brazil (gamma) and California (epsilon), and additional variants continue to be identified.

As long as the SARS-CoV-2 virus spreads, mutations will continue to occur and new variants will be found. Researchers will work to determine whether each variant spreads more easily, the impact it has on the severity of illness, and the effectiveness of current vaccines against the variant (Johns Hopkins Medicine, 2021).

VACCINES

The WHO notes that vaccines are a critical tool in the battle against viral diseases, including COVID-19 (WHO, 2021c). Thus, it is important for healthcare professionals to have a general understanding of vaccines, including their effectiveness against variants, types of vaccines, and common reasons individuals may hesitate to receive a vaccine.

Effectiveness Against Variants

Concerns about the effectiveness of COVID-19 vaccines against variants are widespread. When people hear the words mutation and variants, they may assume that something seriously different about the changed virus will render a vaccine ineffective.

In reality, although vaccines may be somewhat less effective against some COVID-19 variants, vaccines have clear public health and lifesaving benefits for the public. COVID-19 vaccines have been, or are being, tested against many different coronavirus mutations, and research indicates that vaccines already authorized or currently in development will be effective even with a fair amount of antigenic drift in the SARS-CoV-2 virus. Therefore, people should not avoid vaccination because of concerns about new variants (Elterman, 2021; WHO, 2021c; Nightengale, 2021).

Types of Vaccines

There are several basic strategies used to make vaccines. One type of vaccine, live-attenuated, contains live, weakened virus with a limited ability to reproduce. Vaccines for measles, mumps, Rubella, chickenpox, and varicella are made in this way. In live-attenuated vaccines, because the virus does not reproduce effectively, disease does not occur due to the vaccine. However, vaccine viruses are able to replicate just enough to induce “memory B cells” in the body, which then protect against future infections. An advantage of using live, weakened viruses is that one or two doses typically provide life-long immunity. A disadvantage is that persons with weakened immune systems usually cannot receive this type of vaccine (CHOP, 2021).

Another type of vaccine, inactivated, contains virus that is completely inactivated (killed) using a chemical. This “dead” virus cannot reproduce. Examples of inactivated vaccines include polio, hepatitis A, influenza, and rabies. The inactivated virus is still recognized by the immune system, which protects against disease development. Benefits of this type of vaccine are that the vaccine cannot cause even a mild form of the disease, and these vaccines can be administered to people with weakened immune systems. A disadvantage is that it usually requires several doses to achieve immunity (CHOP, 2021).

Using a part of the virus to make the vaccine is another strategy. These are referred to as recombinant, polysaccharide, and conjugate vaccines. Examples include the vaccines for hepatitis B, shingles, and HPV. These vaccines can also be given to people whose immune systems are compromised (CHOP, 2021).

Several COVID-19 vaccines are made by providing the genetic code (DNA, mRNA, or vectored viruses) for part of the vaccine. The immune system recognizes that the genetic code is foreign to the body, and the immune system responds against it. Thus, the next time someone is exposed to the virus, the immune system is ready to provide a rapid response (CHOP, 2021).

COVID-19 Vaccines

Several vaccines have been approved for COVID-19 infection, and others continue to be developed. Information about these vaccines continues to change. (For the most current information about COVID-19 vaccines, see “Resources” at the end of this course.)

• Pfizer-BioNTech: Research indicates that this mRNA vaccine is up to 95% effective at preventing symptomatic disease. Initially, this vaccine had to be shipped in ultra-cold, temperature-controlled units. Now, however, the stability of the vaccine is secured when stored at temperatures more commonly found in pharmaceutical refrigerators and freezers. This vaccine requires two injections, 21 days apart.
• Moderna: Data show that this mRNA vaccine is about 86% effective in people ages 65 and older and 94.1% effective in younger persons. This vaccine requires two injections, 28 days apart.
• Johnson & Johnson / Janssen: This viral vector vaccine was granted emergency use approval by the FDA in the United States. It requires only one injection. A warning label states that the vaccine is associated with an uncommon, but potentially serious, blood clotting disorder.
• Oxford-AstraZeneca: This vaccine is distributed in the United Kingdom and other European countries and is not available in the United States. Its use was temporarily suspended in some countries due to a rare side effect of blood clots with low blood platelets. It requires two doses, four to 12 weeks apart.
• Novavax: As of June 2020, this vaccine is being studied and is not in use. Preliminary data suggest that it is 96.4% effective in reducing mild and moderate disease and 100% against severe disease from the original strain of COVID-19.
  (Yale Medicine, 2021)

Common Reasons for COVID-19 Vaccine Hesitancy

Despite the history of vaccines’ ability to stop disease, some people are hesitant to be immunized in this way. In the case of the COVID-19 vaccine, many reasons have been cited for such hesitancy:

• Distrust of vaccines: Some people believe that vaccines do not work or that they will get sick from the vaccines. Others are concerned that, despite being disproven, there is a link between vaccines and autism disorder.
• Vaccine timeline: Some people are hesitant to be vaccinated because they believe that the COVID-19 vaccine is too new and was created too quickly.
• Effectiveness: People want answers to questions about the effectiveness of the vaccine. Since both COVID-19 and its vaccines are new, some of these questions simply cannot be answered yet. Early studies, however, show that the vaccines are generally safe and effective.
• Side effects: Some people fear possible side effects or long-term complications of receiving a vaccine.
• Lower concern about the virus: Some people and groups do not believe that they are at risk of serious disease from the COVID virus. Or they may believe that the risks of the vaccine outweigh the risks of having the disease.
• Government trust: Research indicates that vaccine acceptance depends on how much people trust their government. For example, in Asian countries where most citizens trust the government, acceptance of the vaccine is nearly 80%. In the United States, acceptance is estimated to be 69%. In countries with low government trust, such as Russia, the acceptance rate is less than 50%.
  (CHOP, 2021)

Part of the vaccine process is addressing the issue of vaccine hesitancy. Experts note that addressing concerns about side effects, safety, registration, and access are critical to the success of any vaccine program.

Suggestions for increasing vaccine compliance and reducing vaccine hesitancy include building trust by having in-person conversations with community leaders such as religious leaders, local elected officials, etc. If community leaders support vaccine use, members of the public are more likely to support it as well (Firth, 2021).

It is also important to improve access to the vaccine, which is another barrier to increasing vaccination rates. Proposals to increase access include:

• Creating a centralized database to help identify at-risk persons
• Simplifying vaccine registration by increasing telephone registration and outreach programs
• Expanding mobile vaccination to target the areas where access is limited
• Establishing programs to administer the vaccine to people who are homebound
  (Firth, 2021)

CONCLUSION

Viral infections are complex processes, with complexity depending on the specific pathogen. Healthcare professionals must be familiar with the viral infection process, mitigation efforts, and vaccine efficacy.

Data show that novel viruses and their mutations have existed for centuries. When such viruses cause a pandemic, it is imperative that global, cooperative action be taken. Healthcare professionals must be able to educate patients/families about how viruses are transmitted, how to reduce spread, treatment measures, and vaccine administration and to dispel myths and inaccurate information.

Vaccines are essential to controlling the spread of these pathogens. Accurate information about vaccine administration, safety, and side effects should be provided through healthcare channels, including patient and family education and community outreach such as print or visual media tools.