In my previous article on this subject, I asked the question: COVID-19: Pandemic or Paranoia? Well, time has definitely brought clarity. The WHO declared on March 12, 2020, that COVID-19 is a pandemic. What this statement does is to provide public health officials guidance regarding the rate of contagion. It is a validation of the lived situation on the ground, and it provides a realistic assesment of the global condition without the myopia of politics. But the extreme containment measures put in place by public health authorities should not make us resentful; they are a consequence of them stepping up to do their job of keeping the population safe. The biggest concern for health providers is that a lot of very sick people will show up all at once, and that equipment like ventilators, hospital beds, personal protective equipment, and even personnel become the limiting factors for care. That would trigger the nightmare scenario of existential triaging – providing the younger most likely to recover with care, and precluding others because they are too sick or too old. The term “flattening the curve” means managing the contagion so that facilities will outnumber the sick, so everyone can have access to care.
The self-protective impulse is a good thing, and paranoia plays an important part in the social reaction to disease. When humans first started agricultural settlements and grew enough food to trigger a population explosion, previously unknown and lethal diseases emerged. Airborne, waterborne, vector-borne and contact pathogens exploded with so many fresh and immunologically naïve bodies to infect. In response, sequestering oneself away from infected people became a natural and protective reaction. Over time, a prophylactic impulse also was triggered. Thucydides, circa 430 BCE, recognized that people who had recovered from smallpox did not contract it again. The Chinese were among the first, over one thousand years ago, to use the crusts of smallpox to inoculate previously uninfected people, and this practice spread to India and Turkey, and later to Europe and to the Americas. In 1777, George Washington ordered mass inoculation of his Continental troops against smallpox. In 1796, Edward Jenner used cowpox to cross-protect against smallpox since both the deadly smallpox and the benign cowpox are members of the same family of viruses called “Vaccinia”. Thus was the term “vaccination” born. A vaccine for COVID-19, the disease caused by the coronavirus SARS-CoV-2, is in the works, but unlike the ancient practice of variolation, vaccination in these modern, litigious times requries a robust program of testing for efficacy and safety, followed by scale-up, formulation, and delivery. Extensive testing is important. A lyme vaccine, LYMErix, which was eventually removed from market had adverse effects in some people in the long term but the vaccine had only been tested for one year before approval. Long term effects could not have been predicted, and nobody wants that repeated for COVID-19. The one good thing that has come from this pandemic is that the protective public health role of vaccination has finally been acknowledged, even by skeptics.
Much new information has emerged in the last month regarding this coronavirus. This article will be a collection of random facts. I will provide a short background to the history of this infection and coronaviruses in general. Then I will review some of the new information regarding how the virus crosses species barriers, causes infections, and the treatment and outcomes of infections. Note that the term SARS-CoV-2 refers to the virus, and COVID-19 to the disease.
Cast your mind back to the days leading up to New Year 2020. A novel coronavirus that caused a SARS-like acute respiratory distress had been identified. It had seemingly originated in a live animal market in Wuhan in Hubei province of China. Coronaviruses are not new to science. They were first described in 1963, and are exclusively associated with warm-blooded animals: birds and mammals. There are four types of coronaviruses, alpha-, beta-, gamma- and delta-coronaviruses, of which only alpha- and beta-coronaviruses infect humans, usually producing mild upper respiratory symptoms such as colds. Their genetic material is a 30,000-base long ribonucleic acid (RNA), which encodes a shell made of protein with a halo of spikes (see Figure 1). These spikes are docking molecules that target them to bind to surface molecules on human cells. Other coronaviruses including the alpha and beta varieties circulate in animals such as civet cats, camels, bats, and pangolins, and their spikes dock with surface molecules of that species. Random mutations in the genetic material can cause a related shapeshifting of the docking molecules, and cause them to shift in species specificity. This happens a lot with viruses with an RNA genome because RNA mutates very easily compared to DNA. This is why we have to take an annual shot for influenza, an RNA virus, but only an occasional shot for chickenpox, a DNA virus.
In the twenty first century, three beta-coronaviruses, named SARS-CoV (2003), MERS-CoV (2013), and SARS-CoV-2 (2019) randomly mutated their spike protein and crossed the species barrier into humans. Their spike proteins docked with a cell surface enzyme called angiotensin converting enzyme 2 (ACE2). ACE2 is present in lung alveoli, the cardiovascular system and the kidney. Further, these viruses could be efficiently transmitted between humans through respiratory droplets, with SARS-CoV-2 binding to ACE2 ten times more strongly than SARS-CoV, and consequently transmitting more efficiently between people. Then there is another complication. It turns out that the coronavirus spike protein is processed by an enzyme called furin which is present on many visceral organs such as lungs, liver, and small intestine. This may enhance viral binding to other organs and exacerbate the severity of the disease [1].
The death rate from SARS-CoV (10%) and MERS-CoV (30%) were higher than COVID-19 (estimated around 2-4%). But both MERS-CoV and COVID-19 are more severe in people with preexisting cardiovascular damage (CVD). Symptoms of COVID-19 are not merely respiratory; several of the patients later diagnosed with COVID-19 initally went to hospital with heart palpitations and chest tightness. From the data, seems that COVID-19 is particularly serious in people with CVD, although it is not clear if lack of oxygen following pneumonia is the cause of cardiovascular symptoms [2]. Other comorbidities may exacerbate COVID-19’s symptoms. Poor immune function means that the virus gets to replicate without the body fighting back. One of the reasons why this particular virus is much more dangerous for frail or elderly people is because the immune system also becomes less robust as it ages.
Treatment for COVID-19 is symptom-based and scales in severity from barely experiencing discomfort to fever and aches to respiratory collapse. Antivirals have been suggested to mitigate the infection, and over a hundred trials are currently underway around the world. Treatment of fever with ibuprofen (such as Advil) has been discouraged by the World Health Organization, because ibuprofen upregulates the ACE2 enzyme that helps the virus enter cells, potentially exacerbating the infection. Acetaminophen (such as Tylenol) is apparently okay to use instead. The use of ACE inhibitors and angiotensin II type-1 inhibitors or angiotensin receptor blockers (ARBs) also are reported to increase ACE2 enzyme levels. These drugs are often used to treat diabetes and hypertension and may increase potential for infection [3]. Seek professional medical advice before self-medicating with painkillers. The CDC and Surgeon General
recommend to avoid aspirin for virus-related fevers such as influenza and chickenpox as it can potentially cause Reye’s Syndrome (https://www.cdc.gov/mmwr/preview/mmwrhtml/00001108.htm). And remember to avoid alcohol when using acetaminophen – taken together they may cause liver failure.
In terms of long-term outcomes, a follow up of patients who had survived SARS-CoV found significantly higher levels of cardiovascular disease, hyperlipidemia and glucose metabolic disease [2]. Since SARS-CoV and SARS-CoV-2 have a similar structure, recovery from COVID-19 may still predispose to these chronic diseases as well. Thus, it is probably wise to avoid infection regardless of age, despite the apparent protective effects of being young and healthy. Thus, following CDC guidelines for social distancing, washing hands frequently, avoiding gatherings and touching one’s face are important for everyone.
Finally, Figure 1 is a scientifically accurate painting of SARS-CoV-2 entering the lungs. This virus may be dangerous, but it’s beautiful.
Figure 1: This painting depicts a coronavirus just entering the lungs, surrounded by mucus secreted by respiratory cells, secreted antibodies, and several small immune systems proteins. The virus is enclosed by a membrane that includes the S (spike) protein, which will mediate attachment and entry into cells, M (membrane) protein, which is involved in organization of the nucleoprotein inside, and E (envelope) protein, which is a membrane channel involved in budding of the virus and may be incorporated into the virion (an infective virus particle) during that process. The nucleoprotein inside includes many copies of the N (nucleocapsid) protein bound to the genomic RNA.
Acknowledgement: Illustration by David S. Goodsell, RCSB Protein Data Bank; doi: 10.2210/rcsb_pdb/goodsell-gallery-019. URL link at: https://pdb101.rcsb.org/sci-art/goodsell-gallery/coronavirus
References:
1. Mallapaty, S., Why does the coronavirus spread so easily between people? Nature, 2020. 579(7798): p. 183.
2. Zheng, Y.-Y., et al., COVID-19 and the cardiovascular system. Nature Reviews Cardiology, 2020: p. 1-2.
3. Fang, L., G. Karakiulakis, and M. Roth, Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet Respiratory Medicine, 2020.
