The History of Coronaviruses
Human coronaviruses have long been considered inconsequential pathogens causing the "common cold" in otherwise healthy people. However in the past 20 years, to the highly pathogenic new coronaviruses have emerged – severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-Cov). They both emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality.
Coronaviruses are large, envelopes, RNA viruses that can be divided into four genera, alpha, beta, Delta and Gamma. Alpha and beta coronaviruses are known to infect humans. Coronaviruses are ecologically diverse with the greatest variety seen in bats, suggesting that they are the reservoirs for many of these viruses. Domestic animals may serve as intermediate hosts, facilitating recombination and mutation events that allow them to jump species to humans.
In early December 2019, a patient in China was diagnosed with an unusual pneumonia. By December 31, the WHO (World Health Organization) had received notification of a cluster of pneumonia cases of unknown cause from the same city of Wuhan China. This is a city with 11 million people.
Within a few days, researchers at Wuhan Institute of Virology identified a novel coronavirus they called COVID-19.
By February 4, 2020, more than 20,000 cases were reported with almost all of them in China with over 400 deaths. Since then estimates suggest that the size of the epidemic in China began doubling every 6 days. By early March there were only 180 cases reported outside of China including on 11 cases in the United States. At the current time there are cases and ongoing epidemics in every continent on earth except Antarctica. In fact, the number of cases and deaths outside of China is now far greater than the number of reported cases within China.
This has now qualified to be the definition of a pandemic of major proportions.
This is not the first time in the last 20 years that we have been faced with the possibility of a pandemic from novel coronaviruses. SARS in China in 2002 and MERS in Saudi Arabia in 2012 are the other 2 zoonotic coronaviruses that were feared to have the potential to become pandemic.
In 2002 SARS spread from China to two dozen countries via international travel. As the viral genetic sequencing data became available, consensus emerged that bats were the natural hosts and palm civets the intermediate host. The overall mortality rate was 10% and there were higher fatality rates in older patients and those with medical comorbidities. Ultimately classic public health measures brought the SARS pandemic to an end but not until over 8000 individuals were infected and nearly 800 died.
In 2012 MERS was identified in a man in Saudi Arabia who died from respiratory failure. MERS was contained and eliminated in relatively short order; however, sporadic outbreaks probably from repeated zoonotic transmission continue to the present time. It has not caused an epidemic outside of the Middle East. However, during the past 10 years it is caused almost 2500 cases and nearly 900 deaths (case fatality rate of 36%). Again the natural reservoir for MERS is presumed to be bats with the intermediate host being the dromedary camel.
For now it appears as though COVID-19 has a much higher infectivity rate than the other two zoonotic coronaviruses as evidenced by the rapid spread throughout the world but a significantly lower case fatality rate of approximately 2%.
From data generated from genetic sequencing of the COVID-19 virus, it appears that there was a single introduction into humans followed by human-to-human spread. It has 96% myology to a bat coronavirus and therefore bats are thought to be the source of the virus. The intermediate host has not been identified. The epicenter of the epidemic seems to be the Huanan Seafood Wholesale Market in Wuhan where there is the illegal sale of bats for human consumption.
The incubation period for this virus has been reported to be 5.2 days although it is unclear when transmission begins and there is some evidence that virus shedding may begin during the asymptomatic early phase of the disease. Nevertheless, it is likely that most of the secondary infections come from symptomatic individuals not asymptomatic individuals.
The clinical syndrome is nonspecific but characterized by fever and dry cough in the majority of patients with about a third experiencing shortness of breath. Much less frequent symptoms include myalgias, headache, sore throat, diarrhea and rhinorrhea. Cases and children are rare; however, as testing becomes more frequent, the true number of cases and the full spectrum of the disease will become clearer. It is probable that the majority of cases are mild but as many as a third of patients may develop acute respiratory distress syndrome type and require intensive care including respirators. The likelihood of severe cases is increased in persons over 60 and those with comorbid conditions such as heart disease, diabetes or hypertension.
There is no known treatments for on Covid-19. There are numerous agents that are in clinical trials but none of them have been yet shown to reduce the morbidity or mortality of the infection.
Currently the major efforts for controlling this disease are social distancing along with improved personal hygiene particularly handwashing and quarantine of known cases along with personal quarantine by staying at home if you have any respiratory symptoms.
A vaccine against COVID-19 is being pursued by the National Institute of Allergy and Infectious Diseases Vaccine Research Center. During the SARS epidemic, researchers were able to develop a vaccine in 20 months and have since then compressed that timeline to 3.25 months for other viral diseases. Although they hope to move even faster with COVID-19, it may be months or many months before an effective vaccine is developed.
Why Has Covid-19 Become a Pandemic?
COVID-19 reached pandemic status within months of the first recognized case in early December 2019. This occurred because of the high infectivity rate of this novel coronavirus.
Ro pronounced “R naught” is a mathematical term to indicate how contagious an infectious disease is. As an infection spreads to new people, it reproduces itself and Ro tells you the average number of people who will catch a disease from any person who is actively contagious.
If a disease has an Ro of 18, a person who has the disease will transmit it to an average of 18 other people. If the Ro is less than 1, each existing person with an infection will cause less than 1 new infection and the disease will rapidly decline in numbers and eventually died out. If the Ro equals 1, each existing infection will cause 1 new infection. The disease will stay alive and stable but there generally will not be epidemics or pandemics.
If the Ro is greater than 1, each existing infection causes more than 1 new infection and therefore the disease will spread between people. This may result in a significant outbreak, epidemic or pandemic.
The Ro is calculated based on several factors including the infectious period and the contact rate as well as the mode of transmission. The infectious period is the length of time that an individual would typically shed the infectious agent. The contact rate is the frequency with which the contagious individual comes into contact with people who are susceptible. The mode of transmission may be by aerosol (through the air) or by direct contact with bodily fluids. With aerosol transmission, it is not necessary for direct physical contact with the infected person. You can catch the disease by breathing air that has aerosolized infectious agents such as from sneezing and coughing. Diseases that require direct contact are easier to avoid because you need to come into direct contact with an infected person or infected blood, saliva or other bodily fluids to contract them. Therefore, diseases that are airborne tend to have a higher Ro value than those that are spread by direct contact.
Many infectious agents such as the influenza virus are in a very high concentration in the biological fluids such as saliva and nasal discharge and are spread by aerosol from coughing and sneezing; however, if an infected individual touches their nose and then articles around them such as handrails and doorknobs, the virus will be on those areas and a susceptible individual can pick up the virus by "indirect contact" with an infected individual. If the susceptible individual then touches their nose, mouth or eyes, the virus can be easily transmitted to their mucous membranes. This is the strongest argument for frequent and thorough handwashing. In today’s society we have become accustomed to using hand sanitizers; however, old-fashioned soap and water probably work as well if not better.
The science behind the control of a disease is related to these issues. With airborne diseases, “social distancing” is important to try to minimize the likelihood of encountering aerosolized virus. Quarantine of infected individuals prevents them from coming in to contact or close proximity with susceptible persons. "Shelter in place" means that susceptible individuals stay at home and avoid travel to public places as much as possible in order to avoid encounters with anyone who may be actively infected. Sneezing and coughing into the elbow or a tissue can help reduce the amount of aerosol produced. Frequent handwashing is important for both the infected individual to reduce the spread of the infectious agent and for susceptible individuals to reduce the contact with the infectious agent.
It is important to realize that the Ro value applies only when a population is completely vulnerable to the disease. This would occur when no one has been vaccinated, and no one has had the disease before, therefore, no one has natural immunity. This combination of conditions is rare in infectious disease because most diseases have been around for many years and therefore many people have natural immunity and for many infectious diseases, we have available vaccines that give people immunity.
The value of Ro for the influenza virus in the 1918 Spanish flu epidemic has been calculated to be 2.8. When this virus came back in 2009, its Ro value was estimated at 1.5 because of the existence of natural immunity and the influenza vaccine that is encouraged every year.
By contrast, mumps has an Ro value of 10 and measles a value of 18. These are extremely infectious agents spread primarily by aerosol. The Ro value of the influenza virus is approximately 1.5.
Although preliminary, the estimated Ro for the COVID-19 virus is thought to be between 1.4 and 6.5 with the best estimate at approximately 3.0. This makes it approximately twice as infectious as the influenza virus that we deal with every year but significantly less infectious than some of the childhood diseases that are now being well controlled by childhood vaccination.
Mortality Rate from Covid-19 Infection
COVID-19 virus and the current epidemic have certainly struck panic and fear in the hearts and minds of all Americans and probably the majority of the world. But are the dire death predictions on-track? There is certainly reason to think that we really do not know the true mortality rate from this infection and the rates that are being quoted may well be grossly inflated. The true mortality rate is calculated based upon the number of people developing the infection who die, not the deaths from identified positive cases. The latter rate is misleading because of selection bias in testing. The degree of bias is uncertain because available data are limited.
If the number of actual infections is much larger than the number of proven cases then the true fatality rate is much lower as well. That is not only plausible but likely based on what we know so far. Of course, the true numbers will not be known until all this is over.
In the meantime, one thing is certain: Health officials seem to be way more concerned about COVID-19 than they have been about other diseases that have had solid, known epidemic numbers for years. For example:
-Opioid Overdoses claim more than 130 people per day. If nothing else this is tantamount to mass homicide, and governments, health agencies and even insurance companies are complicit in this epidemic. Yet, aside from a bit of hand-wringing and lawsuits brought on by various state attorneys general, there are no panicked calls to shut down life as we know it to stop these deaths and address them head-on.
-Obesity is an epidemic. in the U.S. and in many developed countries worldwide, yet there has been no call for the research into the causes of this epidemic that is thought to affect the majority of Americans. 40% of Americans are obese with 8% morbidly obese. Another 32% are overweight. That leaves only 22% of American adults who are at a healthy weight. Obesity contributes significantly to an increase in mortality and a significant increase in the economic cost to the health care system. Obesity has been cited as a contributing factor to approximately 200,000-400,000 deaths in the United States per year and costs society and estimated $117 billion. It is my belief that obesity is rooted in inappropriate food choices, but the food industry has been permitted to confuse the issue by shifting the focus and discussion to exercise and faux fixes like low-fat options, completely omitting the importance of your specific food choices.
-Medical mistakes kill over 250,000 people in United States is is an epidemic that practically no one talks about. It is the third leading cause of death in the United States after heart disease and cancer. Interestingly, one of the top ways patients can be injured is from a hospital-acquired infection. This is why I would suggest that at this time with the viral pandemic, you should not go to the hospital or emergency room unless your situation is life-threatening. Because sick people are in the emergency room and hospital, you will be far more likely to be exposed in that setting then you will be at the supermarket.
-Influenza is a virus that has been with us for many years. The CDC estimates that in the 2019-2020 influenza season there will be 50,000,000 flu illnesses with 500,000 hospitalizations and 50,000 deaths. If we compare this to the number of known COVID-19 cases throughout the world and number of deaths throughout the world, I can only wonder why we have not had the same fear and panic about influenza that we now have about COVID-19. Worldwide, I can only wonder what the death rate is from influenza each year.
What is disturbing to me is the number of patients who tell me they do not want to get an influenza vaccination each year "because it doesn't work." The reality is that the influenza virus that we get this year is based upon the influenza that caused the epidemic last year and the predicted mutational changes that might occur in the virus for the coming year. Vaccine manufacturers are always one year out of sync with the influenza virus which is obviously smarter than we are.
In addition, a large percentage of people still go to work and do not shelter at home or practice social distancing and probably don't even practice good personal hand-washing hygiene to help reduce the transmission of this devastating disease.
-Polio has been a disease that has been with us for many years; however, in 1916 a polio epidemic started in New York City and raged across the country. Many people were affected by this. We all remember Pres. Franklin D Roosevelt who was afflicted by polio. Closer to home, my great uncle died from this disease as a child and my great aunt was left crippled for the rest of her life. Polio epidemics continue to occur sporadically in the United States until the Salk vaccine was developed in 1954. The last polio case in the United States was reported in 1979. Worldwide vaccination efforts have greatly reduced the frequency of this disease in the rest of the world, although it is not yet completely eradicated. The frequency of polio has decreased by over 99% since 1988 when there were more than 350,000 cases worldwide. In 2017 there were only 22 cases reported. Today only three countries still have occasional sporadic cases of polio (Pakistan, Afghanistan and Nigeria). These countries have not been effectively compliant at mass vaccinations of the population particularly the children. Until this occurs, polio will remain a potential threat to the world and particularly the children. Currently in the United States, polio vaccinations are required of school-aged children. This requirement needs to continue until polio has been eradicated worldwide. If the polio virus was imported back into the United States, it could spread rapidly among the un-immunized population.
-Smallpox is a disease that has probably been around for at least 3000 years but one of the first recorded epidemics was in Rome in A.D. 165 when returning soldiers brought smallpox back to Rome from the wars against the "barbarians". It is thought to have killed 5 million Romans. Smallpox continued to be a problem however the death rate in Europeans was only 30%. On the other hand when Europeans came to the Americas smallpox and other illnesses contributed to the collapse of the Inca and Aztec civilizations. Some estimates suggest that 90% of the indigenous population in the Western Hemisphere was killed off by European diseases.
Smallpox once one of the world's most feared diseases was eradicated by a collaborative global vaccination program led by the WHO. The last known case was in some only in 1977. Smallpox was officially declared eradicated in 1979. This eradication was due to a massive vaccination program worldwide. This effort underscores the importance that vaccinations have played in making the world a safer place.
-Measles is experiencing significant increase in cases worldwide this year. WHO estimates that there are already close to 500,000 confirmed cases throughout the world including the United States. Unfortunately even with the implementation of routine immunization, measles continues to circulate globally due to sub-optimal vaccination coverage. Any community with less than 95% immunity is at risk for an outbreak. This is why it is so important for everyone to comply with immunization recommendations. Measles is a highly contagious agent. Remember from the information above, the Ro is 18 which is essentially off the scale.
In the United States between 1985 and 1992, the case fatality rate was 0.2%; however, in countries where malnutrition is a problem, the fatality rate in children can be as high as 25%.
In 2018, there were more than 140,000 measles deaths globally. This was mostly among children under the age of five. The WHO estimates that between 2000 and 2018, more than 23 million deaths were prevented by measles vaccinations. This makes measles vaccination one of the "best buys" in public health history. Currently in the United States, school-age children are required to have MMR (measles mumps and rubella) vaccinations in order to attend school. Unfortunately in some groups there is a resistance to complying with this rule because of the fear of causing autism in their children. There is absolutely no credible scientific evidence that vaccinations cause autism and overwhelming evidence that vaccinations prevent devastating diseases with the accompanying morbidity and mortality.
There are some interesting historical facts about measles. It probably first emerged in A.D. 500 and probably emerged as a zoonotic disease from rinderpest a disease in cattle called cattle plague. When measles was first imported to the Americas in the 1500s, an outbreak in Cuba killed two thirds of the natives and half the population in Honduras and Mexico. Between 1855 and 2005, measles has been estimated to have killed over 200 million people worldwide. In the United States, measles was eliminated in 2000 but unfortunately continues to begin to reintroduced by international travelers.
-Rubella is a preventable disease with the rubella vaccination creating protection and more than 95% of individuals with a single dose. Although the case fatality rate from rubella is low, the big concern is that if women reach the childbearing age without developing community there is the possibility of developing infection during pregnancy. The miscarriage rate is extremely high and the pregnancies that do not miscarry are at risk of developing congenital rubella syndrome. Nearly 50% of women who develop rubella in the first trimester and do not miscarry will have an infant with congenital rubella syndrome. Symptoms of congenital rubella syndrome include congenital cataracts, deafness, heart and brain defects. Infections contracted in the second half of pregnancy are generally not affected.
In 1965 in the United States, an estimated 12.5 million people got rubella, 11,000 pregnant women lost their babies, 2100 newborns died, and 20,000 babies were born with congenital rubella syndrome. Currently WHO reports that there are approximately 100,000 cases of congenital rubella syndrome in the world each year. In the United States, there are fewer than 10 people each year that are reported to have rubella. The last baby born with congenital rubella syndrome was over 25 years ago. Mass immunization programs with MMR are the reason for this dramatic decrease in this potentially devastating disease.
The Ro for rubella is estimated to be 6.
-The Black death is caused by the bacterium Yersinia pestis that was spread by fleas that infested rats and other rodents in the cities of Europe. Over the centuries, there have been many epidemics of bubonic and pneumonic plague. Probably the most important factor that has controlled this disease is public hygiene with your local trash and garbage man being the current day warriors against this disease.
-Alcohol. In 2016, nearly 11,000 people died in alcohol impaired driving accidents. This represented nearly a third of all traffic related deaths in the United States. Nearly 100,000 people in the United States die annually from alcohol-related causes. Over 25% of Americans engage in binge drinking and nearly 10% are consistent heavy drinkers. Both of these groups would be classified as having an alcohol use disorder. When I was growing up the name for these people were "drunks."
-Tobacco. Cigarette smoking is responsible for nearly 500,000 deaths per year in the United States including 50,000 deaths resulting from secondhand smoke exposure. This represents approximately 20% of the death toll in the United States annually. This is 1300 deaths every day. On average, cigarette smokers die 10 years earlier than non-smokers. It is reassuring that the percent of adults currently smoking is less than in the past; however, there is currently an epidemic of "vaping" which may be equally as bad as cigarette smoking.
I am not trying to trivialize the death toll from COVID-19, and I certainly am not saying say that COVID-19 is something to ignore, but I am trying to point out that there are many things that we have already come to accept and live with that are also killing humans. In the same fashion, we will need to learn to accept and live with COVID-19.
Dr. Albrecht's Perspective
We need to be prepared for the likelihood that COVID-19 will be with us forever. Given the Ro infectivity number and how fast and far it has spread already, the best that we could hope for is that we will find ways to deal with it in the near future.
There are theoretical reasons to think that it may become a seasonal disease similar to the influenza virus. It is interesting to note that the number of cases in the Southern Hemisphere is less than in the northern hemisphere and the rate of increase in the number of cases has been slower; however, if indeed it is a seasonal disease, we can anticipate that the Southern Hemisphere will start to see an increase in the rate of new cases as they transition into the colder seasons.
One of the reasons that influenza is so persistent is that even when the rates of influenza are high in the Northern Hemisphere and low in the southern hemisphere as the seasons change, the virus is imported into the opposite hemisphere by international travelers. Therefore, influenza always makes a comeback every year even when the seasonal epidemic seems to be stopped.
There are new studies show that warm, humid weather might slow the virus which could mean the pandemic will ease in the coming summer months in North America and Europe; however, we need to be ready as I predict that it will come back in the fall and winter.
In the meantime, we do need to continue to think about social distancing and shelter in place. More importantly if we are ill, we should consider it our responsibility to stay at home to avoid exposing other people to our colds, influenza or COVID-19.
There are experimental vaccines that will soon be ready and offered to hospital staff and first responders. The speed with which these have become available is astonishing. Whether they will be effective or not remains to be determined. Our healthcare workers and first responders on the front line of the COVID-19 crisis will be the "guinea pigs" for this experiment. Our thanks need to go out to them for so many reasons.
As we move forward, I want to encourage everyone to take seriously their responsibility at protecting themselves and their community by taking advantage of an annual influenza vaccination as well as an annual COVID-19 vaccination should it become available.