Long-Term Complications of COVID-19
Emerging evidence suggests COVID-19 can manifest as more than just acute respiratory illness. Several articles have reported cases of lung injury, cardiac injury, and cardiovascular complications associated with COVID-19.1,2,3 Neurocognitive and mental health impacts are another area of concern.2 Cases of severe inflammation with unknown long-term implications have also been reported in both adults and children.4 Below is a brief summary of the current understanding of COVID-19 related complications:
Studies in China suggest that a high percentage of hospitalized COVID-19 patients exhibit signs of lung damage.2 Some of this damage may develop into pulmonary fibrosis, accompanied by lung function decline. The burden of pulmonary fibrosis after COVID-19 recovery could be substantial as pulmonary fibrosis is a recognized sequela of acute respiratory distress syndrome (ARDS), and 40% of COVID-19 patients develop ARDS according to current data.1
Although the long-term consequences of COVID-19 related lung damage is yet to be determined, the time to recovery of lung function is likely to be long when looking at SARS and MERS as past examples. In SARS patients, declined lung function took over two years to recover, and 4.6% of patients still show lung abnormality after 15 years.1 In MERS, about a third of patients showed signs of pulmonary fibrosis after about 40 days following hospital discharge.1
Initial studies suggest up to one in five hospitalized COVID-19 patients exhibits signs of cardiac damage.2,5 The damage may be due to the body’s overwhelming systemic immune response, known as cytokine storm, but it could also be due to the virus directly infecting the heart.5,6,7 The heart has many ACE2 receptors, which have been identified as a cellular entry point for the SARS-CoV-2 virus. Cardiac damage can have a lasting impact. There is evidence that COVID-19 patients develop cardiomyopathy or myocarditis, reducing the heart’s ability to circulate blood around the body.8
Due to the inflammatory response to the infection, some COVID-19 patients have coagulation abnormalities, which elevates the risk of lung blockages, strokes, and heart attacks.2 Venous thromboembolism is seen in up to one-third of acutely ill patients with COVID-19.9 Two studies in France suggest that 23-30% of severe COVID-19 patients also have pulmonary embolisms.2
These cardiovascular complications are serious and can have lasting impact. To this, the American College of Cardiology has updated their guidance regarding use of anticoagulation therapy and management of venous thromboembolism (VTE) in response to COVID infection and complications.10
Neurocognitive and Mental Health Impacts
It is not uncommon for severely ill patients to experience neurological symptoms such as dizziness, headaches, vision, taste/smell impairment, etc. Past SARS and MERS epidemics suggest COVID-19 could also cause long-term neurocognitive problems. Research shows one in five ARDS survivors experiences long-term cognitive impairment, including short-term memory problems and difficulty with learning and executive function even five years after discharged.2
Additionally, ARDS survivors have increased rates of depression, anxiety, and PTSD long after the acute phase of the disease.2,3 Furthermore, a recent British study provided direct evidence that COVID-19 leads to acute neurological and psychiatric complications, especially in younger patients.11 Longer-term surveillance will provide additional insights into potential chronic impact.
Although children have been the minority of COVID-19 cases, there are new concerns of a novel, severe inflammatory response similar to Kawasaki disease.4 Affected children experience persistent fever, rash, and swollen extremities. It is unclear if the COVID-19 related Kawasaki-like disease will have any long-term impact, but a past study on Kawasaki disease indicates patients can suffer myocardial and vascular complications in adulthood.2
COVID-19 Impact on Biopharma R&D
R&D Unmet Needs due to COVID-19 Sequela
Although it is too early to determine the true magnitude of the long-term complications among COVID-19 survivors, the scale of the pandemic would suggest that there is an elevated level of unmet need to manage COVID-19 associated long-term complications in the years to come. For perspective, there were approximately 8,000 cases during the SARS epidemic and approximately 2,000 MERS cases to date, worldwide. In comparison, we have over 26 MM confirmed COVID-19 cases worldwide and over 6 MM cases in the US as of September 4, 2020.12 This suggests there will be a significant number of patients experiencing long-term complications even if the incidence rate is low. Although there are existing treatments to manage various COVID-19 related complications, the increased demand presents an opportunity for the biopharma industry and should motivate the research and development of novel therapies to manage these complications more effectively.
As companies work on novel therapies to address COVID, and its many severe complications, there is promising news of use of existing therapies offering life-saving benefits, but when used with caution and care. Beyond the now approved Remdesivir from Gilead, and case reports showing benefit from dexamethasone,13 Regeneron and Lilly are testing REGN COV2 and LY-CoV555, respectively – both monoclonal antibody approaches to neutralizing and possibly treating the SARS-CoV-2 coronavirus itself.14,15
Additionally, leading biotechs and pharma are working on immune-mediated approaches with long-approved medicines. Roche’s Actemra, targeting IL-6, has recently posted generally negative results, while SOBI’s Anakinra targeting IL-1, and Lilly’s Olumiant targeting JAK 1/2 are still being studied.16
Beyond these well-known and available therapies, many biotechs and pharmaceuticals, large and small, are conducting studies of novel molecules in a global and urgent effort to address the virus.
Greater Demand for Infectious Disease Drugs
Beyond the COVID-19 related complications, the pandemic has generated an unprecedented level of public awareness of infectious diseases, which is likely to have a lasting impact on patients’ healthcare-seeking behavior. As a result, we expect the infectious disease therapeutic category to be poised for growth. There will be greater recognition of the burden of disease for infectious diseases, particularly respiratory illnesses such as influenza, RSV, and human metapneumovirus. Patients are more likely to seek care when experiencing symptoms and request testing, resulting in an increased level of diagnosis of other infectious diseases following the pandemic. Additionally, recognizing that we currently have a weakness in our response to infectious disease, governments may look to reduce development barriers, increase commercial incentives, and invest in innovation to combat infectious disease. These factors should collectively incentivize biopharma companies to increase their R&D efforts in infectious disease, which has traditionally been a therapeutic area with fewer development activities.
COVID-19 has put a tremendous amount of strain on the U.S. healthcare system. As we slowly start to shift our attention away from treating the acute symptoms, we are only beginning to understand the scale of the long-term complications from COVID-19 survivors. The biopharma industry has an opportunity here to help society transition back to normal by conducting studies to understand the scope of the COVID-19 related complications, developing novel treatments that can manage the complications more effectively, and investing in R&D for infectious disease, so we could better respond to a future outbreak.
|About the Authors|
Steven Chang, Ph.D. is a Senior Analyst in the Health Advances Newton office.
Yinzi Liu, Ph.D. is an Engagement Manager in the Health Advances San Francisco office.
Doug Mullen, Ph.D. is a Director in the Health Advances Newton office.
Wyatt Gotbetter is a Partner in the Health Advances Newton office.
 Spagnolo et al., 2020, Lancet Respir Med, 8(8): 750-752.
 Parshley, Vox, published Jun 12, 2020, accessible at: https://www.vox.com/2020/5/8/21251899/coronavirus-long-term-effects-symptoms.
 Klitzman, New York Times, published Jun 4, 2020, accessible at: https://www.nytimes.com/2020/06/04/opinion/covid-19-survivors-effects.html?searchResultPosition=6.
 Viner et al., 2020, Lancet, 395(10239): 1741-1743.
 Hawryluk, Scientific American, published Apr 6, 2020, accessible at: https://www.scientificamerican.com/article/heart-damage-in-covid-19-patients-puzzles-doctors/.
 Siripanthong et al., 2020, Heart Rhythm, 17(9): 1463–1471.
 Pesheva, Harvard Gazette, published Apr 14, 2020, accessible at: https://news.harvard.edu/gazette/story/2020/04/covid-19s-consequences-for-the-heart/.
 Pizada et al., 2020, CJC Open, 2(4): 278–285.
 WebMD, accessible at: https://www.webmd.com/lung/coronavirus-complications#1.
 Bikdeli et al., 2020, J Am Coll Cardiol, 75(23): 2950-2973.
 Varatharaj et al., 2020, Lancet Psychiatry, S2215-0366(20)30287-X.
 John Hopkins University Coronavirus Resource Center, accessible at: https://coronavirus.jhu.edu/map.html.
 RECOVERY Collaborative Group, 2020 N Engl J Med, NEJMoa2021436.
 Regeneron Press Release, published Jul 6, 2020, accessible at: https://investor.regeneron.com/index.php/news-releases/news-release-details/regeneron-announces-start-regn-cov2-phase-3-covid-19-prevention.
 Lilly Press Release, published Aug 3, 2020, accessible at: https://investor.lilly.com/news-releases/news-release-details/lilly-initiates-phase-3-trial-ly-cov555-prevention-covid-19-long.
 Roche Press Release, published Jul 29, 2020, accessible at: https://www.roche.com/investors/updates/inv-update-2020-07-29.htm.