UNDERSTANDING VIRUSES, THEREFORE HOW THE SARS-CoV-2 WORKS…(PART I)

What is a virus? A virus is a submicroscopic infectious agent that makes copies of itself in certain conditions inside the living cells of an organism.  A virus can disrupt any type of living forms from microorganisms such as bacteria to plans and animals.  Until now more than 6k types of viruses have been described in detail out of the millions of types of viruses that are on our biosphere. Note that any ecosystem on the earth involves viruses and is the most ubiquitous type of biological entity.

How the infection takes place. When an organism gets infected, the virus “hacks” a host cell provoking to create thousands of identical copies of the original virus. An important difference here is when the infectious agent is not inside an infected cell or in the process of infecting a cell, the virus exists in the form of an independent agent called VIRION which consists on genetic material based on long molecules of DNA or RNA that encodes the structure of the proteins, then is the protein coat or the “capsid” which surrounds and protect the genetic material and lastly in many cases is the “envelope” made mostly of lipids. When we talk about shapes and forms, those range from helical or icosahedral forms to complex structures they are one-hundredth of the size of a common bacteria, so they are quite small.

Structure_of_HIV
Structure of HIV (AIDS) – National Institute of Allergy and Infectious Diseases (NIAID).          Credit: National Institutes of Health (NIH)

Their origin and the debate if they are living things or not. The origin of viruses still needs to be further investigated, there are some theories that tie their origin on the pieces of DNA that can move between cells also known as plasmids and some others from the bacteria directly. Anyway, viruses are quite important due to its capability to increase genetic diversity across all lifeforms and there are some debates around how do we need to consider them, there are claims where consider the virus a life form because they “carry” genetic material and could reproduce but at the same time there are characteristics that are not those that define a usual cell or bacteria structure, therefore viruses can be coined as agents that are on the “edge of life” or replicators.¬†

How the spread works. They spread in many ways, one is through disease-bearing organisms known as “vectors”, in this case, viruses are transmitted between the same species e.g. plant to plant but by insects that feed on plant sap or between animals carried by blood-sucking insects. Most known for all of us are those related to influenza transmitted by coughing or sneezing or the “rotavirus” transmitted through the fecal-oral route in the previous contact with food. Others such as AIDS disease where are transmitted through contact with infected blood or sexual contact. In virology terms, the term “host range” is the variety of host cells that can be infected by the virus to understand the spectrum on how the virus can infect a few species or have broader impact.

Immune response. When a virus infection occurs, an immune response usually eliminates the infecting virus, but when this one is aggressive, immune responses must be induced by a vaccine which provides an artificially acquired immunity to the specific virus, some other cases such as AIDS or viral hepatitis evade these immune responses where a chronic infection could happen, therefore a parallel treatment is based on antiviral drugs, in both cases takes time to run the clinical trials to get massively produced solutions for larger populations. 

Immune responses in viral sepsis. (A) Normal competent response to viral infection resulting in clearance of infection (1) When the immune system is exposed to a virus, the virus infects or is phagocyted by macrophages. Phagocytes break down, process and present antigens from the virus and produce type 1 cytokines. (2) Type 1 cytokines cause T cells to differentiate into T H 1 cells and CD8 T cells. (3) T H 1 cells and CD8 T cells cause apoptosis of infected cells and activate processes such as the production of reactive oxygen species in phagocytes, which destroy the viruses. Antibody production is elevated, resulting in greater phagocytosis and destruction of viruses. (4) Virus is cleared and memory T cells are produced, which can rapidly respond to future infections. (B) Aberrant immune response resulting in viral sepsis and failure to clear virus. (1) When the immune system is exposed to a virus, the virus infects or is phagocytosed by macrophages.. Phagocytes break down, process and present antigens from the virus. Non-type 1 cytokines are produced. (2) Non-type 1 cytokines result in inappropriate type 2 or type 17 immune responses, which cause inflammation but cannot clear the virus. (3) T cells become exhausted and can no longer competently clear pathogens.
Article cite: Lin, Gu-Lung & McGinley, Joseph & Drysdale, Simon & Pollard, Andrew. (2018). Epidemiology and Immune Pathogenesis of Viral Sepsis. Frontiers in Immunology.

Viruses and relation with human diseases. There is a large range of human including the common cold, influenza, chickenpox and cold sores, but among these diseases are other more aggressive such as rabies, Ebola, HIV, SARS, MERS, and obviously SARS-CoV-2 that causes COVID-19, so “virulence” is another term used to determine the level of the associated diseases. Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between¬†human herpesvirus 6¬†(HHV6) and neurological diseases such as¬†multiple sclerosis¬†and¬†chronic fatigue syndrome.¬†

 Ebola hemorrhagic fever symptoms. Photo Credit: Center for diseases control and prevention.

Viruses mechanism of action. Viruses have different mechanisms by which they produce disease in an organism, which depends largely on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In¬†multicellular organisms, if enough cells die, the whole organism will start to suffer the effects. Although viruses cause disruption of healthy¬†homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the¬†herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency¬†and is a characteristic of the herpes viruses, including Epstein‚ÄďBarr virus, which causes glandular fever, and¬†varicella zoster virus, which causes chickenpox and¬†shingles. Most people have been infected with at least one of these types of herpes virus.¬†These latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as¬†Yersinia pestis.

Some viruses can cause lifelong or chronic infections, where the viruses continue to replicate in the body despite the host’s defense mechanisms. This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus. In populations with a high proportion of carriers, the disease is said to be endemic, that could be the case of SARS -CoV-2.

How the SARS РCoV Р2 works, then. Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range of about 2 meters. Contact via contaminated surfaces is another possible cause of infection, preliminary research shows that the virus may remain active on plastic and stainless steel surfaces for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours; the virus can be deactivated from the exposed skin by soap, which destroy its lipid bilayer. 

Human sneeze image sequence analysis showing how droplet ejection works, therefore potential to spread infection. The image capture a 20 msec incremental sequence of the sneeze cloud of a healthy person. Image credit: The New England Journal of Medicine.
Infographic showing lifetime of SARS-CoV-2 on surfaces. Image Credit: Business Insider with data from New England Journal of Medicine, The Lancet Microbe.

Level of infection. The defined level of the virus to determine how infectious is during the¬†incubation period¬†needs to be further investigated, but as preliminary estimations, it shows that the peak¬†of the viral load¬†takes approximately four days after infection¬†or the first week of symptoms, and declines after this period. On 1¬†February 2020, the¬†World Health Organization¬†(WHO) indicated that “transmission from¬†asymptomatic¬†cases is likely not a major driver of transmission”.¬†However, an epidemiological model of the beginning of the¬†outbreak in China¬†suggested that “pre-symptomatic¬†shedding¬†may be typical among documented infections” and that¬†subclinical infections¬†may have been the source of a majority of infections.¬†Similarly, a study of ninety-four patients hospitalized in January and February 2020 estimated patients shed the greatest amount of virus two to three days before symptoms appear and that “a substantial proportion of transmission probably occurred before first symptoms in the¬†index case”.

Virus structure. The SARS-CoV-2¬†virion¬†is 50‚Äď200¬†nanometres¬†in diameter. Like other coronaviruses, SARS-CoV-2 has five structural proteins, known as the S (spike), E (protein), RNA (genome), and the envelope. The S, E, and M proteins together create the¬†viral envelope where the spike protein is responsible for allowing the virus to attach to and fuse with the¬†membrane¬†of a host cell allowing the virus their “corona or crown” shape under the microscope.

SARS-CoV-2 Structure. Image Credit: Wikimedia Commons

SARS-CoV-2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response such as:

  • Colonization of a niche in the host (this includes the ability to attach on human cells)
  • Evasion of the host’s immune response.
  • Inhibition of the host’s immune response.
  • Entry into and exit out of cells (if the pathogen is an intracellular one).
  • Feed from the host.

Symptoms

Symptomatology: Signs and symptoms may appear from two to fourteen days after being exposed to infected people where the incubation (estimated) timeframe happens. Signs and symptoms can include:

  • Fever
  • Cough
  • Tiredness

Other symptoms can include:

  • Shortness of breath
  • Muscle aches
  • Chills
  • Sore throat
  • Loss of taste or smell
  • Headache
  • Chest pain

This list above is not inclusive since other less common symptoms have been reported, such as rash, nausea, vomiting and diarrhea could occur. Children have similar symptoms to adults and generally have mild illness.

The severity of the symptoms can range from fully asymptomatic, very mild, severe, or even fatal. Some people may have only a few symptoms, and some people may have no symptoms at all. People who are older or who have underlying medical conditions, such as heart disease, lung disease, diabetes, severe obesity, chronic kidney or liver disease, or who have compromised immune systems may be at higher risk of serious illness. This is similar to what is seen with other respiratory illnesses, such as influenza.

Author: Jesus Padilla

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