Author: Abinaya Arulalagan

COVID-19 is the disease caused by SARS-CoV-2 which can vary in severity greatly between patients, as is common with respiratory diseases.  With no known pre-existing immunity against COVID-19 in humans, the World Health Organisation (WHO) has stated that everyone is at risk of infection. This is supported by the epidemiologic characteristics of the spread of COVID-19 in China. Certain risk factors, however, increase susceptibility to infection. Although the most crucial morbidity factor is exposure to an infection source, underlying health issues, age, and even gender could influence our susceptibility. Misinformation has blurred the line between science and fiction; it is time to understand what truly causes an increased risk of contracting COVID-19.

AGE OF THE POPULATION

As the epidemic unfolds, it has been noted that the elderly are particularly prone to developing an acute form of COVID-19. With more than 50% of deaths being in those aged 80 and over, many theories have been developed. One is that their immune system cannot control its response to SARS-CoV-2 which triggers an overproduction of immune cells and cell signalling molecules [11]. The cytokine storm that follows [11] is what triggers severe inflammatory diseases such as pneumonia. This “aggressive reaction” can also be seen when the virus replicates faster than the response of the immune system. Hence, 70+-year-olds have been placed in the highly-vulnerable sector and are encouraged to self-isolate for up to 4 months in the UK [10].

Fig 1: The death rate of COVID-19 by age group [11]

Whilst children can also be infected with COVID-19, they appear to have significantly milder symptoms or even be asymptomatic (where an infected person who doesn’t display symptoms).

This is one of the many attributes that set SARS-Cov-2 apart from other viruses. Conceivably due to a different mechanism of attack, it tends to flourish in developing or underdeveloped immune systems [8]. There is speculation that antibodies (which are proteins produced by leukocytes or white blood cells) are transferred to the baby via breast milk during breastfeeding which may play a role in providing a form of unknown immunological protection. There is no scientific evidence however to support the involvement of natural passive immunisation, which lasts until children reach 4-months, in COVID-19 [1].

PREGNANCY AND NEWBORN

The potential risk of vertical transmission of COVID-19 has become a major concern. Through homology modelling [10], it has been uncovered that SARS-CoV-2 and SARS-Cov-1 have similar receptor-binding domain structures and possibly a similar invasion stage. This, alongside the study by Chen and colleagues, which did not find SARS-CoV-2 viral particles either in the conception products or in neonates, the theory was supported that there is limited risk of vertical transmission of SARS-Cov-2 from mother to baby. It is critical to remember that the brief duration of Chen’s study and the inadequate sample size may limit the reliability of the data. With only 3 neonatal cases so far in the pandemic and an undetermined source of infection, there is currently no scientific evidence to suggest that SARS-CoV-2 causes problems with fetal development or delivery, or can even be transmitted across the placenta.

Also, a clinical study by the WHO in which only 1% of 148 pregnant women with suspected or confirmed cases of COVID-19 participants in the 3rd trimester were in critical condition. Yet, pregnant women tend to be more susceptible to typical respiratory pathogens and the development of severe pneumonia [10]. Thus, pregnant women and newborn babies are still considered to be key at-risk populations in mitigation and management strategies of COVID-19 infection.

The casted fatality rate in a clinical study for Severe Acute Respiratory disease (SARS) stood at 15% whilst. No pregnant woman suffering from COVID-19 in the clinical study had died. This distinct difference in severity in pregnant women between SARS-Cov-2 and other respiratory pathogens may imply a mechanistic difference in terms of attack.

GENDER

With the death rate in China in mid-February of 2.8% for men and 1.7% for women, women have a slightly lower risk of becoming infected due to a more resistant immune system. This is attributed to the presence of steroid hormone estrogen which stimulates the immune system, which testosterone inhibits [8].  Some speculate that a mutant variant of the ACE-2 gene on the 'X' chromosome (a receptor-coding gene which allows SARS-Cov2 to enter host cells) may increase susceptibility to COVID-19. As women have two 'X' chromosomes, females would still be able to produce one functional copy of the gene, compensating for the mutant variant, unlike men, who have one 'X' and one 'Y' chromosome. Yet, scientists have been quick to point out that this observation has been noted in a sample of only 45,000 patients; the sample is not large enough to suggest a gender disparity.

UNDERLYING HEALTH ISSUES

WHO-recognised independent risk factors include cardiovascular disease, diabetes, hypertension, chronic respiratory disease, and cancer. Although some may be surprised to consider diabetes as a risk factor for COVID-19, it is a metabolic disorder: accumulation of activated immune cells in tissues leads to the release of inflammatory mediators, which promotes insulin resistance. This not only reduces the function of white blood cells but also causes multiple complications once infected with COVID-19 such as highly fluctuating blood sugar levels [2]. Importantly, patients suffering from diabetes and hypertension are often treated with ACE inhibitors or angiotensin II type-I receptor blocker (ARBs), which increases the expression of the ACE-2 gene (angiotensin-converting enzyme 2) in lungs, facilitating infection of the cells by SARS-Cov-2.

Furthermore, Ibuprofen boosts the expression of ACE inhibitors, which may explain why some are declaring that Ibuprofen [5] can cause symptoms to worsen. This is why medical health organisations have stated that whilst there is no definite evidence to suggest that it is threatening to take Ibuprofen whilst infected with COVID-19, Paracetamol should be taken instead. Patients taking Ibuprofen for other conditions should not stop without consulting a doctor.

Cancer patients - those both suffering from cancer and those receiving treatment - are considered to be one of the most vulnerable groups due to their highly immunocompromised state, making the severe acute respiratory disease a more likely occurrence. How high this risk is, varies by individual too: the type of cancer, patient history, treatment, and pre-existing chronic conditions. It is vital to note that those who are in survivorship care or those who have finished chemotherapy treatment are not at risk. Local GPs have advised them, however, to remain inside.

CHILDREN AND YOUNG ADULTS

Yet, even young, healthy people die from the disease. For example, the death of Li Wenliang, a Chinese 34-year-old doctor, could be attributed to both genetic and environmental factors. Rasmussen’s work proved that genetic factors are key in viral infections, but the specific genetic variants have not yet been identified. In respect to potential environmental factors, the expression of symptoms and disease may be linked to viral load [9] -  how much virus is replicating in a tissue. If you are infected with a high viral load, perhaps due to someone persistently coughing in your face, your immune system is less likely to be able to cope. Unfortunately, it is not known whether the asymptomatic person carries a high or low viral load. Although it may be easy to speculate, more clinical studies need to be done to understand the implications of viral load.

Recognising trends in increased severity of the disease within subsets of the whole population is crucial for both individuals and the community to take the necessary precautions. Strong scientific evidence is needed to support this and, thus, consistent funding for long-term studies is pivotal in implementing effective mitigation strategies. Everyone, especially those identified in key-risk groups must follow national guidelines by authorised medical bodies and stop misinformation.


Biography: Abinaya Arulalagan is a 17 year old student from London, England. She loves to try new things whenever she can and binge-watch documentaries. With a passion for all things neuroscience-related, she hopes to study Medicine at University.


References:

  1. Baxter, D. 2007. “Active and Passive Immunity, Vaccine Types, Excipients and Licensing.” Occupational Medicine 57 (8): 552–56. https://doi.org/10.1093/occmed/kqm110.
  2. “Coronavirus and Diabetes | What to Know.” 2020. Lark Health. March 10, 2020. https://www.lark.com/blog/coronavirus-and-diabetes/.
  3. cinj.org. (n.d.). COVID-19: What Cancer Patients Need to Know | Rutgers Cancer Institute of New Jersey.https://cinj.org/patient-care/covid-19-what-cancer-patients-need-know [Accessed 5 Apr. 2020].
  4. Fang, Lei, et al. “Are Patients with Hypertension and Diabetes Mellitus at Increased Risk for COVID-19 Infection?” The Lancet Respiratory Medicine, vol. 8, no. 4, 2020, doi:10.1016/s2213-2600(20)30116-8.
  5. March 2020, J.B.-L.S.E.-C. 15 (n.d.). Newborn tests positive for COVID-19 in London. [online] livescience.com. https://www.livescience.com/newborn-has-coronavirus-london.html [Accessed 5 Apr. 2020].
  6. Monitoring, R.C. team and B. (2020). Coronavirus and ibuprofen: Separating fact from fiction. BBC News. [online] 17 Mar.https://www.bbc.co.uk/news/51929628 [Accessed 5 Apr. 2020].
  7. Mullins, E., D. Evans, R. M. Viner, P. O’Brien, and E. Morris. 2020. “Coronavirus in Pregnancy and Delivery: Rapid Review.” Ultrasound in Obstetrics & Gynecology, March. https://doi.org/10.1002/uog.22014.
  8. Qiao, Jie. “What Are the Risks of COVID-19 Infection in Pregnant Women?” The Lancet, vol. 395, no. 10226, 2020, pp. 760–762., doi:10.1016/s0140-6736(20)30365-2.
  9. The Scientist Magazine®. (n.d.). Why Some COVID-19 Cases Are Worse than Others. [online] Available at: https://www.the-scientist.com/news-opinion/why-some-covid-19-cases-are-worse-than-others-67160
  10. TODAY.com. (n.d.). Who is exposed to high “viral load” of COVID-19 and why does it matter? [online] .https://www.today.com/health/coronavirus-what-does-viral-load-mean-when-it-comes-covid-t177438
  11. Vally, H. (n.d.). Why are older people more at risk of coronavirus? [online] The Conversation. http://theconversation.com/why-are-older-people-more-at-risk-of-coronavirus-13377011.
  12. Yang, Jing, et al. “Prevalence of Comorbidities in the Novel Wuhan Coronavirus (COVID-19) Infection: A Systematic Review and Meta-Analysis.” International