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What we know, what we still don’t and why there is reason to be hopeful
By Adarsh Bhimraj, MD
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COVID-19, the infectious disease caused by the SARS CoV-2 virus, needs no introduction. Within a span of a few months, it has become a pandemic that has spread around the world like wildfire. Along with the pandemic has also spread panic, fears and fictions. Indeed, there is still much we need to learn about this virus, its biology, clinical features and treatments, but it is also true that we have learned a great deal about the virus in the last several months.
It’s well understood that the SARS-CoV-2 virus is highly effective in its ability to spread from human-to-human. Some early studies estimate that the reproduction number (R0) is likely between 2 to 2.5.1 R0 is the number of cases, on average, an infected person will cause during their infectious period. Simply put, one person with the infection can spread it to 2-3 people.2
However, what clinicians and researchers are working to piece together are the clinical predictors of severe disease, and how to prevent and treat it. At this point, we just don’t have good evidence about which patient characteristics, especially those that can be modified, are more likely to lead to acute, life-threatening disease. In response however, some smaller studies examining patients infected early on in the outbreak are examining comorbidities and other patient demographics that may affect disease pathology.
One study examined 139 patients in Wuhan, China, hospitalized with COVID-19. Of these patients, 46.4% had one or more coexisting comorbidities. Among the most common included, hypertension (43 [31.2%]), diabetes (14 [10.1%]), cardiovascular disease (20 [14.5%]), and malignancy (10 [7.2%]).3 This study also found that the median age of infection was 56 (IQR, 42-68; range, 22-92 years) and that the majority of patients infected were men (75 [54.3%]). Anecdotally, these findings have been somewhat consistent with the patients whom I’ve treated, but there are still outliers — and, of course, this varies by location.
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The virus carries RNA and is enveloped in a membrane. It is killed by the use of soap, detergents and water. Because of its spread via respiratory droplets, social distancing is an effective strategy to reduce person-to-person transmission. Researchers are also learning more about SARS-CoV-2 and its viral entry point via angiotensin converting enzyme II (ACE2) receptors. By way of its characteristic spike proteins, the virus gains access to host cells in the human respiratory tract, thus initiating the pathogenesis. Analysis has shown that this binding process of the SARS-CoV-2 to the ACE2 is 10 to 20 times more likely to occur than that of SARS-CoV, which explains the comparatively higher R0 of the novel virus.4
These early discoveries about the disease pathogenesis establish a framework for therapeutic development that may lead to treatment for infected patients or a vaccine to prevent transmission of the virus. Right now, there are no proven therapies to treat COVID-19, but there are some existing drugs being administered through clinical trials and through compassionate use protocols. Still, safety and efficacy profiles remain unknown at this time.
Though still theoretical, it’s important to mention two aspects of the treatment paradigm. There are antiviral drugs like hydroxychloroquine, remdesivir, and lopinavir/ritonavir that are thought to kill the virus, as well as drugs like tocilizumab, sarilumab (Interleukin 6 receptor blockers) and steroids, that are presumed to help control a patient’s inflammatory response caused by the virus, as some of the damage could be from excessive inflammation. These medications are not entirely benign and have adverse effects that may harm patients. We currently don’t know if the benefits of using these medications outweigh potential harms. While in some cases, these efforts are already underway, the quicker we, as the medical community, can enroll these patients in clinical trials and start getting data, the quicker we can deliver evidence-based treatments.
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The outbreak of the SARS-CoV-2 virus is likely to fundamentally alter aspects of the healthcare system. The allocation and supply of personal protective equipment is a big part of the equation in the discussion of global pandemic preparedness, but considerations will likely be made around local preparedness policy, inventories and cross-training primary care physicians and emergency room staff — not just infectious disease specialists. Even interpersonal interactions in healthcare settings, like shaking hands with your physician or in-person visits might look different in the future.
In Albert Camus’ 1947 novel The Plague he writes, “What’s true of all the evils in the world is true of plague as well. It helps men to rise above themselves.” While the COVID-19 outbreak has been, and continues to be, a calamitous global health event, as clinicians we should be heartened by the strides we’ve made in a relatively short period of time to understand the disease and conduct accelerated trials to find effective and safe therapies. While this pandemic may forever shift some aspects of our lives, certainly within the healthcare system, there is still reason to be hopeful. The pace at which research and guidance are emerging, with people across disciplines and countries coming together to combat the pandemic — is truly remarkable.
Dr. Bhimraj is a staff physician in the Department of Infectious Disease at Cleveland Clinic, and is also section head of Neurologic Infectious Diseases.
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