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.