COVID-19: Why does it affect people differently?

Posted by Dr Blerida Banushi 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that has caused the COVID-19 pandemic. It infects the respiratory system via small droplets from coughing and sneezing. The virus enters the body through the mouth, nose or eyes, and hooks onto healthy cells in the airway with spikes that give it its crown-like appearance. The virus binds itself to the cell’s receptor, called ACE2, normally found in our lungs, kidneys, heart and gut. The virus then injects its genetic material, ribonucleic acid (RNA), into the cell and rapidly begins replicating itself to spread multiple copies of the virus down the throat, trachea and lungs.

Usually, our bodies respond by activating an immune response that destroys the infected cells. However, viruses have ‘learned’ to evade the immune system and ‘host specific’ factors to aid their escape, which explains why individuals respond differently.

The clinical spectrum of COVID-19 is extremely broad, ranging from asymptomatic to serious multi-organ and systemic reactions that resemble overzealous and lethal reactions. These severe reactions are similar to those experienced by patients in intensive care who are suffering from systemic sepsis, septic shock, and multiple organ dysfunction syndrome (MODS).

Recent studies estimate that around 45-80% of infected individuals are silent carriers, showing no or very mild symptoms. However, these individuals are still able to transmit the disease to others without knowing it. It’s important to underline that testing would need to be performed across whole populations to have more accurate rates of the proportion of asymptomatic individuals.

It’s not known exactly why some individuals with SARS-CoV-2 are asymptomatic, while others develop severe illness, but a number of risk factors have been associated with the disease.

One factor to consider is the viral load, which measures how much of the virus is replicating itself and surviving in the body. Children have been shown to be more asymptomatic, even though their immune system is still immature. Their innate immune system (the first but non-specific defence mechanism to defend the body from infection) appears to be greater than adults. This can lead to a reduced viral load because hypothetically they can quickly clear the virus without it reaching their lower respiratory system.

Although it may seem counter-intuitive, reduced levels of the ACE2 receptor (found in elderly people, and those with chronic lung disorders) put affected individuals at greater risk of an excessive inflammatory response, called ‘cytokine storm’, which causes severe lung disease. Levels of ACE2 receptor are higher in children, which has also been correlated with asymptomatic infections.

A second part of the viral response takes longer to establish and is called ‘adaptive’. This type of immune response is specific to pathogens (or a vaccine) and has memory, making it efficient at fighting infections when the body is presented with the same pathogen. Although specific genetic variations have been shown to play a role in how quick the adaptive immune response is generated (which reduces the viral load during the incubation period), an individual’s health has been found to be critical in the process.

Healthy individuals have a stronger immune system that can prevent infection, and it’s invasion of the lungs. Individuals who smoke, are immunocompromised, or suffer respiratory diseases, have impaired immune systems.

Old age has also been associated with poor health outcomes in COVID-19 patients, as well as hepatic and kidney function abnormalities, increased C-Reactive Protein (CRP), decreased albumin, increased lactate dehydrogenase enzyme (LDH), hypertension, and high cytokine levels. Adults in the 70–80-year-old age group have a case fatality rate of 8.0%, and adults above age 80 have a case fatality rate of 14.8%. The likelihood of additional pre-existing conditions increases with age and this makes older adults more susceptible to developing severe disease. Asymptomatic transmission is a constant threat to the elderly population.

COVID-19 patients with diabetes are especially at high risk of severe disease and mortality, due to several factors such as impaired immune response and increased inflammatory response.

Studies have also found correlations between COVID-19 and blood groups, with blood group A possibly being more susceptible to the disease, and blood group O being more protected.

Obesity has been shown to be another risk factor for severe SARS-CoV-2 infection, independent of a person’s age, diabetes, and hypertension. It also raises the risk of needing mechanical ventilation (IMV), especially in individuals with a BMI ≥35 kg/m2, aggravate respiratory function, obstructive sleep apnea, and inadequate and excessive immunological responses.

Researchers have also found significantly higher SARS-CoV-2 mortality rates in males than in females, possibly due to hormonal and immune system response differences.

Strong correlations have also been made between nutrition and exercise, and immune cells and inflammation. Studies have linked moderate-intense exercise to reduced risks of contracting SARS-CoV-2, and increased immune functions that boost the body against the virus. This is true not only for the coronavirus, but also influenza, pneumonia and several other infectious diseases.

A growing body of data also suggests Vitamin D deficiency may also be associated with  severe SARS-CoV-2 infection.

Correlations have also been made with poor air quality, causing weaker airway defence mechanisms and an increased risk of death from SARS-CoV-2 in North Italy. The same correlation has been found in China where elevated concentrations of air pollutants were found in heavily affected COVID-19 regions. By contrast, the lockdown-related reduction in fine inhalable particles (PM2.5) is considered to have reduced SARS-CoV-2 transmission.

The numerous factors that influence a person’s risk of catching SARS-CoV-2 serve as a timely reminder of the comments made by WHO Director-General Dr Tedros Adhanom Ghebreyesus during his opening remarks at the World Health Assembly:

‘The pandemic is a reminder of the intimate and delicate relationship between people and planet. Any efforts to make our world safer are doomed to fail unless they address the critical interface between people and pathogens, and the existential threat of climate change that is making our earth less habitable’.

The ‘Prescriptions for a healthy and green recovery from COVID-19’ include the protection and preservation of the source of human health: Nature, and an investment in essential services such as water, sanitation and clean energy in healthcare facilities. This will ensure quick healthy energy transition, promotion of healthy and sustainable food systems, building healthy and liveable cities, and stop using taxpayers money to fund pollution (WHO- 26 May 2020).

Blerida BanushiDr Blerida Banushi

Dr Blerida Banushi is a postdoctoral researcher at UQ-Diamantina Institute. She did her PhD and first postdoc at the University College London in membrane protein trafficking. Her current work is highly translational and is based at the Translational Research Institute in collaboration with the PA hospital.


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