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24 March 2020
Let history tell us who is most at risk of contracting COVID-19

(Published - 24 March 2020)

There is concern and alarm among officials, as well as the medical and scientific communities, about the possible impact the coronavirus disease COVID-19 could have should it spread among the most overcrowded and poorest areas in South Africa.

Why the anxiety? It points to the fact that these areas typically have the highest incidence of immuno-compromised individuals – malnutrition, tuberculosis and HIV are commonly rife in these areas.

Some coronavirus history is required. We currently know of seven coronaviruses that affect humans, in addition to the +30 that circulate among animals. Four of these seven human coronaviruses, or hCoVs – known as hCoV-229E, hCoV-NL63, hCoV- OC43 and hCoV-HKU1 – are community-acquired and have circulated through the human population continually for a very long time, and are among the numerous viruses responsible for the common cold.

These community-acquired coronaviruses have been shown to affect the immuno-compromised and the elderly, resulting in more severe symptoms. Then we know of three more pathogenic coronaviruses. These are the Severe Acute Respiratory Syndrome coronavirus (Sars-CoV), which caused an outbreak of the disease “severe acute respiratory syndrome” (Sars) in mainland China and Hong Kong in 2003; the Middle East Respiratory Syndrome coronavirus (Mers-CoV) that led to an outbreak of “Middle East Respiratory Syndrome” (Mers) in, among other countries, Saudi Arabia, the United Arab Emirates, and the Republic of Korea in 2012; and now, Severe Acute Respiratory Syndrome Coronavirus (Sars-CoV-2), which causes the outbreak of “Coronavirus Disease 2019”, aka COVID-19.

For all three deadly human coronaviruses, advanced age, being a male, and the presence of other pre-existing medical conditions - including obesity, diabetes, heart disease, lung disease, kidney disease - are the major factors linked to severe disease and death. This is not to suggest that the young, youth and women are immune to the disease. In coronavirus and other infections, the infected person’s innate immune system - consisting of physical, chemical and cellular defences against disease-causing pathogens - provides the defence against the pathogen or germ.

Once the pathogen manages to evade the physical barriers and enters the body, an immune response is triggered, which involves the release of, among other things, inflammatory proteins known as cytokines, whose job it is to regulate the immune response. The main purpose of the innate immune response is to stop the spread of the pathogen in the body.

Unfortunately, researchers are showing that this immune response to the coronavirus could be the main reason for lung tissue damage during coronavirus infections. Research suggests that, with conditions like COVID-19, in a small number of people, the immune system “overreacts” or overcompensates. This leads to the overproduction and release of cytokines, which can lead to organ failure and death. The implications are complex and still not well understood.

Could this mean, for instance, that someone with a weaker immune system could be at lower risk of developing severe COVI-19? Sars-CoV and Mers-CoV have never been reported to cause a more severe disease in immunosuppressed patients. Data for Sars-CoV-2 is currently less conclusive. Some researchers, looking at a small group of cancer patients with immuno-suppression, reported a higher risk of developing adverse effects. Other COVID-19 research is showing that patients with cancer and post-transplant immunosuppression are at similar, lower risk as the non-immuno-compromised to develop severe COVID-19.

To my knowledge, no death has yet been linked to Sars-CoV, Mers-CoV and Sars-CoV-2 in patients undergoing chemotherapy, transplantation, or other immunosuppressive treatments – all conditions that lower the body’s immune system – regardless of their age.

So what does this mean for someone with immunodeficiency, such as HIV-Aids, but taking anti-HIV treatment? To speculate, we need to look at history and the most studied human coronavirus to date. I know of only one reported case of an HIV-positive person infected with Sars during the 2003 outbreak. This person recovered fully from Sars. During the same period, another study reported the connection between HIV and Sars. Interestingly, despite contact between the 95 patients confirmed positive for Sars and 19 HIV-positive individuals in a hospital ward, none of the HIV-positive patients became infected with the Sars-CoV.

Also interestingly, six of 28 medical personnel who worked in the ward were infected with the Sars virus. Researchers speculated that the anti-HIV treatment provided some protection against SarsCoV infection. It is too early to tell if we will see the same for Sars-CoV-2, but does this provide us with hope? With COVID-19, we are beginning to identify those most at risk, based on early findings in many countries, including China and Italy. One of the pressing questions on people’s lips is why do we see the high numbers of infected and deaths in a developed country such as Italy?

Studies would suggest that the highest fatality rates are among the elderly – some 23% of Italy’s population is aged 65 and older, compared to around 6% in South Africa – and those with pre-existing medical conditions, known as comorbidity. These comorbidities included heart disease, stroke, hypertension, diabetes, dementia and chronic lung disease. A study that came out over the last few days reports that up to 85% of COVID-19 fatalities in Italy were in older patients with multiple comorbidities.

There is another group at risk. Lessons learnt from Sars and Mers show us that this is the world’s healthcare workers. With Sars, for instance, over 8 000 cases and about 800 deaths were reported from 29 countries, and healthcare workers comprised 21% of these cases. Likewise, a study on Mers infections found that healthcare workers made up nearly 19% of cases. There is a similar concern in Italy, where 8.3% of healthcare workers and 20% of family doctors were infected with COVID-19 as reported on March 17 and 18, respectively.

It would be interesting to see how many of the COVID-19 positive patients were infected by these medical personnel. So, will we see the same happening in South Africa? The scientific answer is that it is too early to tell. But what can we learn from Italy? Adequate training of medical staff to effectively handle this pandemic, without placing themselves at risk, is crucial. Protective measures, such as gloves and masks, should be mandatory for all medical staff seeing any patient, with or without obvious respiratory symptoms, during this period.

For the elderly, on the other hand, minimising exposure to any respiratory disease threat is essential. In nursing homes, this means that strict hygiene precautions should be implemented and that any residents showing any flu-like symptoms should be quarantined immediately.

Concern over immuno-compromised patients is understandable, but past experiences with Sars and Mers suggests that they are not an at-risk group. Questions remain, of course, and only time will tell whether COVID-9 will behave similarly. What is clear, however, is that we should be putting in place the means to protect our elderly and those with pre-existing medical conditions. And, critically, our healthcare workers. Our health systems are notoriously frail. Without our healthcare workers, it will be even more so.

Professor Fielding is the University of the Western Cape’s Research Development director and the lead researcher at the Molecular Biology and Virology Research Laboratory at UWC.