It’s certainly an understatement to say that there is so much that we don’t yet understand about COVID-19 or the virus that causes this illness (technically referred to as SARS-COV-2, but we’ll use term COVID-19 here for ease). Given how quickly the virus spreads and takes hold in our communities, we have had little time to study its impact on specific populations and explore potential treatments. As a healthcare marketing firm working with companies promoting pharmaceutical therapies, our staff often reviews clinical studies to better understand the meaning of this research in terms of patient health outcomes and risks. At no time has this been more valuable—on a personal level— than it is right now during the pandemic. Yet the lack of proven clinical evidence and clinical trials means that even those of us who work in healthcare are often trying to project and predict the potential impact of this virus with largely anecdotal reports.
However, there is still some exciting, emerging COVID-19 research going on right now, and new reports and studies are being initiated and examined every day. Given the vast amount of information being disseminated, we’ve tried to summarize what we feel are some of the most interesting areas of study, theory and research for you here. Below are some of the early insights and data points we’ve collected amidst this rapidly-changing crisis. They represent just a few key areas that are important for anyone in healthcare to follow.
What we do know: Risk factors, illness progression and how the virus takes hold.
We do have some understanding of how this virus attacks our cells and impacts our organs and body, thanks to research on similar illnesses like SARS, as well as our knowledge from studying other types of flus and coronaviruses. And we also know a lot about the risk factors that seem to predispose people to more serious illness.
And in fact, to understand the risks and comorbidities that can lead to more severe illness or even death in those infected, it helps to understand how COVID-19 replicates itself and how that impacts the body. The novel coronavirus latches on to a common receptor—ACE2—found in human lungs and the small intestine as well as in other organs like the kidneys and heart. (These organs are frequently damaged in more serious COVID-19 cases leading to issues like heart attacks and kidney disease.) ACE2 receptors are a part of the sympathetic nervous system, and their job is to bind to the ACE2 hormone as part of the body’s overall response to stress. The ACE2 hormone helps constrict blood vessels, which then raise our blood pressure.
In fact, COVID-19 research has shown that high blood pressure is one of the most prominent risk factors for the progression of the virus, so that’s certainly something that researchers and clinicians will be examining closely. This relationship between the ACE2 receptors, blood pressure and certain comorbidities may give us a clue about what’s really going on in some patients with severe illness. For example, people with diabetes and high blood pressure often take drugs called ACE inhibitors. These drugs actually make our bodies create more ACE2 receptors. Some scientists are looking at whether this is why people with these conditions have more severe cases of COVID-19. However, this is just a theory and it’s important to note that US heart groups have issued guidance telling patients NOT to discontinue these drugs.
Additionally, it’s useful to note that inhaling nicotine has an impact on ACE2 receptors in the lungs, which is also being studied right now. This is especially important in light of the vaping epidemic in young Americans, as it’s expected that vaping has the same impact on these receptors as smoking regular cigarettes. Interestingly, some studies have noted that smokers are actually under-represented in COVID-19 cases, especially in China. However, smokers who were infected had more severe disease progression. (With all of the other risk factors associated with smoking and vaping, now may end up being a good time to encourage people to quit the habit regardless!)
We also understand a lot about the course the illness takes from recent COVID-19 research. For most people (approximately 80 percent), the virus will not take hold aggressively in the lungs and they will not experience the more serious form of infection. Calling this illness “mild” may be a misnomer, as many individuals still feel like they have a serious case of the flu. They will likely experience the most common symptoms—fever, cough, body aches and shortness of breath—for some time. (A few interesting studies are showing that even with the mildest form of the illness, the loss of a sense of taste or smell may be one of the most common symptoms.) It can still take days, or even weeks, to recover from COVID-19, but these individuals won’t require oxygen supplementation, or even worse, ventilator support, which has been associated with poor outcomes in certain patients.
For those that do progress to more serious illness, this typically happens in the second week, after experiencing milder symptoms along with more concerning ones like significant trouble breathing. Many clinicians tell COVID-19 patients who are isolating at home that keeping an eye out for this particular symptom, and that testing their oxygen levels with a pulse oximeter daily is a great way to ensure that they don’t need hospitalization. Some people decompensate very quickly once they reach this point. Because by now, acute pneumonia has taken hold, making it more difficult for their body to get oxygen to cells, all while the immune system is trying to mount a strong defense to attack the virus. (In fact, an overresponse by the immune system is one theory why, in rare cases, younger people seem to succumb to the virus.)
Unfortunately, for the 20 percent of individuals who do need to be hospitalized, around five percent will require intensive care and many of those will be sedated and placed on ventilators. According to some early studies from China, nearly half of those critically ill patients may not survive. (Obviously this data from Wuhan may not apply within our healthcare system, but it’s troubling nonetheless.) Most of those individuals will be older, although as we mentioned, in very rare cases the virus has led to severe illness and even death in those far younger.
For those with a more aggressive form of infection, the illness results in severe pneumonia and even organ involvement, which can lead to failure of the kidneys and even heart attacks. This is also why certain chronic conditions are more serious risk factors. According to many early studies and the CDC, the highest level of risk is found in individuals over 70 and those with heart disease, diabetes and obesity, as well as individuals receiving steroids and other immunosuppressants (including transplant patients), and to a lesser extent, those with asthma, COPD and cancer.
What we will know: Clinical trials and studies in progress.
As we write this, there are countless researchers applying their collective brainpower across the globe. As a result, there are some really exciting COVID-19 research studies and trials in progress, as well as some very interesting theories being tested that may tell us a lot about what we can expect—even if we can’t predict the future with absolute certainty.
For example, we’re currently working with largely incomplete data about potential therapies, but never before have researchers been so focused on a single mission. This means some incredible work is being done in the field and in labs simultaneously. Certainly, the hydroxychloroquine/chloroquine anecdotal evidence is particularly compelling, especially given the fact that China ordered a huge supply of the drug several weeks ago and countries around the globe have added it to their treatment protocols. In addition, while a first study out of France was maligned by many as less than rigorous in its research methods, a second report authored by a French infectious disease specialist has shown promising results for hydroxychloroquine used in combination with a common antibiotic. While there was no control group in the research, the author continues to document clinical improvements in patients given both hydroxychloroquine and azithromycin. As a result of this early research and other anecdotal reports from the field, the FDA has just issued an emergency authorization which will allow the dissemination of millions of doses of these drugs for use in treating COVID-19.
Chloroquine has been used for decades to prevent malaria, and hydroxychloroquine is commonly used in treating many autoimmune conditions. Both may have antiviral properties as well as immune-modulating effects. (Chloroquine has been studied as a potential therapy against other coronaviruses including SARS.) Both have been proven to be fairly safe, even with long-term use. Some potential side effects of hydroxychloroquine include an impact on the retina—and less so—issues with heart arrhythmias. Chloroquine must be administered carefully, however, because there is a very small difference between a therapeutic and toxic dose. In addition, Remdesivir, another antiviral, is showing some early promise. Still, it is not yet in widespread use, so less is known about its safety profile.
As all of these drugs are antivirals, we can assume they may need to be administered fairly early to be most effective. (For example, in commonly-used antivirals like Tamiflu, they must be taken within the first day or two of illness to shorten both its duration and severity, which may hold true in the case of COVID-19 as well.) However, getting these drugs to patients quickly during a shortage of testing and supplies is challenging for even the most advanced healthcare systems.
As interesting as these early anecdotes may be in theory, we still need some stronger data from COVID-19 research to support these ideas. That’s exactly why the World Health Organization (WHO) is developing a large-scale clinical trial of hydroxychloroquine, Remdesivir and two other therapies. These trials will study their impact in patients around the globe.
Because WHO realizes that doctors on the front lines don’t have the time or energy to collect a massive amount of data in the midst of this crisis, they are studying just a few potential outcomes and measurements. Physicians will record the day the patient left the hospital or died, the duration of the hospital stay and whether the patient required oxygen or ventilation. Another exciting facet of this clinical trial is the fact that governing bodies will allow for some early release of data, meaning we won’t have to wait months to see the impact.
At the same time, hydroxychloroquine and Remdesivir are the subject of COVID-19 research and clinical trials in the US, including one interesting trial testing post-exposure administration of the drug in healthcare workers. Another promising trial is testing the use of antibodies from the plasma of people who have recovered, which was a strategy used in China. In the coming weeks, we should start to see some evidence out of clinical trials taking place in China. The country has thus far conducted around 500 clinical trials, including more than 20 analyzing chloroquine’s efficacy, with the remaining looking at antivirals, HIV drugs and even treatments derived from the practice of Chinese medicine.
What we don’t know (but may be interesting in theory).
Especially interesting are various studies about certain vitamins, minerals and enzymes in terms of their immune-modulating effects, including vitamin D, zinc and an antioxidant and potential lung function precursor called N-Acetyl-L-Cysteine. In the case of vitamin D, researchers have long wondered if the low levels of vitamin D most people have in the winter may predispose them to colds and flu. Interestingly, Italy, which has been particularly hard-hit by the virus, does not generally fortify its food supply—like milk and other dairy—with vitamin D.
Zinc has been shown to reduce respiratory illness in some studies. WHO acknowledges that zinc-deficient children are at increased risk of respiratory tract infections including those affecting the acute lower respiratory tract. Again, these are not proven treatments for COVID-19, but may be useful sources of study for boosting immune function. Much more evidence is needed before anyone knows whether these will be useful in preventing infection or duration/severity of illness.
Stay tuned for more data.
In summary, the COVID-19 landscape is rapidly evolving and just trying to keep pace with the sheer amount of theories, clinical studies and trials can be overwhelming. We hope that our summary helped separate at least some of the current theory from evidence, and we’ll keep you apprised of new data points from COVID-19 research as they emerge!