People often say that practising medicine is an art as much as it is a science. In a utopia of health, we would have data from the most rigorous diagnostic and prognostic studies, randomized trials would be conducted for every therapeutic and prophylactic intervention, and all clinical decisions would be evidence based. In reality, however, we practise medicine in an environment far from utopia – one of heterogeneity and uncertainty. No situation illustrates this better than the current COVID-19 pandemic.
In a short amount of time and under very stressful conditions, health care workers, researchers and scientists across the globe have made significant progress in our understanding of the novel coronavirus, SARS-CoV-2, and the COVID-19 illness it causes.
Here are five research discoveries affecting clinical care of patients with COVID-19:
1. Rapid sequence analysis and data sharing help expedite development of diagnostic reagents and vaccines
Within 10 days of the initial report describing a pneumonia of unknown origin in Wuhan, China, the novel coronavirus had been sequenced and its genome was shared on the Internet. Clinical researchers and pharmaceutical companies began developing diagnostic reagents and vaccine candidates immediately. According to the International Society for Infectious Diseases resource ProMED, the first diagnostic test was made available on Jan. 19 — just nine days after the genomic sequence was disseminated. Many more tests were developed and validated for clinical use in the following months; nearly 100 molecular tests are available now. Production and testing of vaccines occurred on a similar timeline. As of mid-July, 163 vaccine candidates are being evaluated and 23 of them are in clinical trials: large-scale phase III trials have been initiated for three of these. If the technology to rapidly isolate and sequence the novel coronavirus had not been available and if researchers had not selflessly shared the genomic sequence, the ability to identify and track infections would have been reduced, possibly resulting in greater spread of the virus and more deaths, and efforts to design vaccines would have been delayed.
2. Proning improves oxygen saturation and reduces the need for mechanical ventilation
Evidence is accumulating to support early anecdotal reports that proning —the process of precisely and safely turning a patient from their back onto their abdomen — helps patients with COVID-19. A study published in JAMA Internal Medicine showed that prone positioning for one hour improved oxygen saturation in 19 of 25 patients with COVID-19 who had severe hypoxemic respiratory failure. Fewer patients with improved oxygenation required intubation compared with patients who did not improve with prone positioning. Randomized trials are still needed to evaluate the efficacy of proning, particularly to determine whether it reduces mortality, but as a relatively safe physical manoeuvre, a trial of awake prone positioning is recommended for patients with persistent hypoxemia if intubation is not otherwise indicated.
3. Identification of coagulopathy markers and recommendations for thromboprophylaxis
Early in the pandemic, patients with COVID-19 underwent a gamut of testing to better understand this new disease. One notable finding was elevated D-dimer and fibrinogen levels, which are more commonly associated with thrombotic complications including disseminated intravascular coagulation (DIC) and venous thromboembolism (VTE). Further, it became evident that abnormal coagulopathy markers were associated with admission to critical care units and increased mortality. This discovery led several hematology groups to recommend routine thromboprophylaxis at the time of hospital admission for all patients with COVID-19 as well as careful monitoring and prompt treatment for sepsis-induced coagulopathy (SIC), DIC and VTE. The pathophysiology of hypercoagulability hasn’t yet been fully elucidated, although tissue damage induced by a cytokine storm in these patients is a likely possibility.
4. New-onset loss of smell or taste is a useful clinical pearl
Many respiratory infections clinically mirror each other, and often it isn’t necessary to identify the causative agent in mild, self-limited illnesses. However, because of the severity of COVID-19 in some patients and the public health impact of the pandemic, diagnosing and tracking COVID-19 is paramount. When testing is limited, focusing testing efforts on patients who are most likely to have the disease may be critical. A few anecdotes about patients with olfactory and gustatory dysfunction led to the inclusion of questions about these symptoms in patient history and observational studies to evaluate the prevalence of these unique features. It is now clear that ageusia (loss of taste) and anosmia (loss of smell) occur in about 80 percent of patients with COVID-19. Since these symptoms are not common in other respiratory infections, ageusia and anosmia have become clinical pearls in the decision to test for SARS-CoV-2.
5. Effective therapies for severe cases
While a cure for COVID-19 remains elusive, two therapies have shown promise for the most severe cases. In two randomized trials, the RNA inhibitor remdesivir shortened the time to clinical improvement in patients admitted to hospital with COVID-19; however, there is insufficient evidence to date that remdesivir improves mortality. These data have led the Public Health Agency of Canada (PHAC) to recommend remdesivir for adults with COVID-19 pneumonia requiring supplemental oxygen. The second therapy recommended by the PHAC for patients with severe COVID-19 requiring supplemental oxygen is the steroid dexamethasone. In one large randomized trial, dexamethasone reduced 28-day mortality among patients receiving supplemental oxygen or mechanical ventilation.
BONUS discovery:
6. Elucidating the crystal structure of the SARS-CoV-2 spike protein
In March, research groups from the University of Texas at Austin and the National Institutes of Health published the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike protein. Because the spike protein is used by the virus to enter human cells, it is a key target for vaccines, therapeutic antibodies, small molecule therapies and diagnostic reagents. Therefore, knowledge of its structure is integral to fighting this pandemic.
There is still so much we need to learn about this novel coronavirus that will affect how we manage the care of patients with COVID-19, including the pathophysiology of severe disease, coagulopathy and multisystem inflammatory syndrome in children (MIS-C). Better understanding the type and durability of immunity to natural infection will also help guide our vaccine strategies. Finally, we must remember that basic research in virology and microbiology is essential, as microorganisms don’t just exist in our world — we live in theirs.
For more information, see the topic COVID-19 (Novel Coronavirus) in DynaMed.
Original article published on EBSCO Health Notes. Written by:
- Vito Iacoviello, MD, Deputy Editor for Infectious Disease, Allergy, and Immunology at DynaMed; and
- Heather D. Marshall, PhD, Senior Medical Writer in Infectious Disease, Allergy, and Immunology and Digital Media Specialist at DynaMed.
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This material is for informational purposes only. It is not intended to be a substitute for professional medical advice and should not be relied on as health or personal advice. The opinions stated by the authors are made in a personal capacity and do not necessarily reflect those of the Canadian Medical Association and its subsidiaries including Joule.