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There is significant controversy about the source of the COVID-19 outbreak. Currently, the earliest known existence of a virus resembling SARS-CoV-2 came from samples harvested from Dead Pangolins brought to the Guangdong Wildlife Rescue Center of China on Oct 24th, 2019. The government of China monitors wildlife to sound the alarm if a potential pandemic strain is detected. Patients ill with viral pneumonia of no known cause began to appear in December in Wuhan, China. The first case was diagnosed on Dec 1st in China and had no apparent link to the market. There were another 41 cases, with 28 associated with the wet market in the city. However, 13 of 41 did not visit the market.
Bats are a known reservoir for these types of viruses. Pangolins are probably not the original source of the virus but were an intermediary host that was infected both with a pangolin coronavirus and a bat coronavirus. As these viruses grew in the pangolin, there was a chance to exchange genetic material in a recombination event, creating the deadly pandemic strain. How did this then make the jump to humans? It appears that the genetic changes to the spike protein of coronavirus made SARS-CoV-2 able to bind to the ACE2 receptor of humans where the parent strains it arose from could not. One hypothesis is that the virus made the jump to humans from a dead pangolin, bat, or other animal. A person that was then ill with COVID-19 entered the market and spread it to others.
The first infection was probably a poor fit between the SARS-CoV-2 strain and the ACE2 receptor of the human host. But, as the virus grew, mutations in the spike protein would occur. Those that had a better fit to ACE2 would have a selective advantage. Thus, the more the virus grew in humans, the more adept it became at infecting them. As it moved from host to host, the efficiency of transmission and replication probably increased. This adaptation of SARS-CoV-2 is not unique. All viruses change and sometimes these changes allow them to infect new hosts.
Coronaviruses have infected humans for millennia, typically causing a mild upper respiratory infection we refer to as a cold. (There are several classes of viruses that cause cold-like symptoms, coronaviruses are just one of them.) Why is SARS-CoV-2 different? In contrast to many viruses, the receptor used and the binding process of coronaviruses vary considerably across each coronavirus variant. The receptor target dictates the host range and tissue specificity. SARS-CoV-2 uses the ACE2 receptor where other, less damaging coronaviruses do not. Using ACE2 gives the virus access to the lungs, heart, kidneys, brain, and gut. As the body fights the infection, it will cause inflammation and damage wherever the virus is growing. As the lungs are damaged, they fill with fluid, causing pneumonia and shortness of breath. If the heart is involved, heart failure and cardiovascular events occur. Infections in the gut cause diarrhea. COVID-19 can cause all of these symptoms.
Everyone appears to be a target for the virus. Recent statistics from the Wisconsin Department of health show the breakdown of infection rates for every age group (Figure 14-2) Not everyone who has COVID-19 is going to experience life-threatening symptoms. Results from an analysis of over 72,000 cases in China paints a clearer picture of the risks of COVID-19 illness. The majority of people (81%) who get infected with COVID-19 will have mild disease, about 14% of cases will cause severe disease, and 5% of cases result in critical infection. Half of the patients who become critically ill do not survive. The death rate of diagnosed cases appears to be between 2.5-5%. Still, most countries are probably undercounting the number of actual cases, either because people are not seeking medical attention or from a lack of testing capacity.
Figure 14.2. Age distribution of those infected by SARS-CoV-2 in Wisconsin. Anyone can contract COVID-19. The higher rates of infection in those older than 20 years old is probably because the illness can be more severe and those patients will seek treatment. Those younger than 20 were probably not as readily tested for the illness. Data taken from the Wisconsin Department of Health.
Why do some people appear to have little to no symptoms, and others struggle with this disease to such a large degree? We are getting a better understanding of important factors that affect the outcome. Your risk of dying from COVID-19 depends significantly on your general health. First and foremost, no one's risk is zero. Previously it was thought that children under the age of 9 did not develop severe illness. However, the state of New York has identified 102 cases of pediatric multi-system inflammatory syndrome caused by SARS-CoV-2 that can be fatal if left untreated. As age increases, the death rates increases, Figure 14-3, but this has more to do with the accumulation of health problems.
The strength of your immune system and its ability to get the infection under control also seems to play an important role. If the virus can replicate to high numbers, it can spread systemically. Viral sepsis, probably by COVID-19, is a strong predictor of adverse outcomes. It appears that if the virus spreads into the cardiovascular system, it may cause damage to the heart and to blood vessels since these cells have the ACE2 receptor. Inadequate organ function due to the infection or pre-existing health conditions is a strong predictor of poor outcomes.
Figure 14.3. Who dies from COVID-19. The figure shows deaths for each age group and the increase in risk for each pre-existing condition. As age increases the death rate also increases. This has more to do with how many preexisting conditions a person has than their age.
The US is at greater risk for complications from COVID-19 infections because the CDC estimates that 45% of the population has at least one of the pre-existing conditions mentioned above. Seven behaviors contribute to the likelihood of complications: smoking, sedentary lifestyle, obesity, diabetes, hypertension, high cholesterol, and inadequate fruit and vegetable consumption. In other words, our bad habits as a society are about to exact their revenge on the population as a whole thanks to COVID-19. If you have one or more of these pre-existing conditions you need to be extra careful to try to avoid COVID-19.
Due to the lack of testing and the inexperience of health professionals dealing with a pandemic, it is highly likely that the number of COVID-19 deaths early in the pandemic was inaccurate. Some argue deaths are being incorrectly attributed to COVID-19, while others claim the situation is leading to an undercount. To answer this question, the CDC did a study of excess mortality in New York City. NYC was an early epicenter of the epidemic, having thousands of active cases. The NYC health department previously developed an electronic vital statistics reporting system that provides a rapid and nearly complete count of all deaths in the city. Using this database, researchers were able to compare the all-cause mortality in NYC in previous years with mortality in the current year. By subtracting a baseline expected death rate, it is possible to calculate the number of excess deaths in 2020. From March 11–May 2, 2020, a total of 32,107 deaths were reported in NYC, which is 24,172 deaths above the expected baseline. Subtracting all reported COVID-19 deaths during this period leaves 5,293 excess deaths. Most of these are probably due to COVID-19, but not all. Some may be from patients who fear or could not seek medical attention due to the epidemic but were not infected with the virus (for example, someone having a heart attack). The large number of excess deaths is compelling evidence that health departments were underestimating the death rate from the epidemic by up to 22%.
Since vaccinations have become available, the situation has probably resolved, and COVID-19 deaths are now being accurately recorded. This is partly due to a better understanding of COVID, but also due to the lower death rate since more of the population is vaccinated. However, far too many people (379 a day in the US in July 2022) are still dying of COVID.