Policy Brief by Summer 2020 MPH Intern Emma Hymel

Text-only version below.

To access the fully formated version click here: Policy_Brief_Final_Draft_-_Emma_Hymel.pdf

 

Key Points:

  • The current pandemic caused by SARS-CoV-2 poses a large threat since not much is known about possible lasting effects of the virus.
  • Previous long-term studies on populations that had been infected with SARS, MERS, and H1N1 demonstrated increased risks of chronic diseases, including pulmonary fibrosis, cardiovascular complications, neurological and psychiatric morbidities, changes in metabolism, and possible autoimmune effects.
  • Possible policy changes include developing a national registry, updated surveillance systems, and creating funding opportunities to support further research endeavors.

Introduction:

Since the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the COVID-19 outbreak has developed into a worldwide pandemic. In addition to the primary and immediate health effects of the virus, not much is known of the long-term health effects of infection. Most people who have experienced COVID-19 believe that once they have recovered, there will be no lasting effects but there is limited data describing recovery. To assess the risks for developing chronic disease following the novel coronavirus outbreak, long-term follow-ups of severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza A (H1N1) can be examined. These widespread respiratory infections had a significant impact on the health of those infected, both during the initial stages of infection, as well as years later. Chronic diseases are already of particular concern as they contribute significantly to morbidity and mortality in the United States, as well as produce a significant economic burden on those affected.

Literature Review:

Respiratory Conditions

Studies of both H1N1 and SARS have demonstrated the lasting impairment of pulmonary function following infection. In a respiratory follow-up of H1N1, impairment, largely due to inflammation, lasted about 2 months (Zarogoulidis et al., 2011). Another study of H1N1 reported 54.2% of study participants had pulmonary dysfunction one year after initial infection, including small airway dysfunction and diffusion disorder (Liu et al., 2015). One year after infection, 28% of a cohort of SARS survivors had abnormal chest radiographs, and many experienced diminished lung capacity, lowered exercise capacity, as well as lowered quality of life (Hui et al., 2009). Furthermore, in a 15-year follow-up of SARS patients, pulmonary fibrosis was common among the cohort; pulmonary function was significantly impaired, although it did improve over many years (Zhang et al., 2020). Pulmonary dysfunction seemed to last longer with SARS than H1N1, although significant impairment was seen with both.

Cardiovascular Conditions

Cardiovascular complications of respiratory infections have been reported during infection, and cardiovascular abnormalities were even reported in a cohort of SARS survivors 12 years following initial infection (Wu et al., 2017). Although stroke in the context of viral infections is rare, deep vein thrombosis, pulmonary embolisms, and large artery cerebral infarctions were found among cases of SARS during periods of hospitalization (Umapathi et al., 2004). In a study of H1N1 conducted by Brown et al. (2011), the virus was shown to impair heart function and contributed tto heart dilation and heart failure in 23 severe cases within one month of infection; this may be more prevalent in cases that require mechanical ventilation.

Neuro/psychiatric Conditions

Previous studies have shown that four human coronaviruses have been associated with neurological diseases; small case studies of MERS also linked the virus to intracerebral hemorrhage and polyneuropathy (Algathani et al., 2016). In addition to these viruses possibly directly infecting the nervous system, the trauma surrounding experiencing these infections, including prolonged isolation, may contribute to psychiatric conditions. Mak et al. (2009) reported that in the 30 months past SARS infection, 58.9% of study participants had developed psychiatric disorders, predominately PTSD, depression, and anxiety, with 33% of the cohort reporting at least one psychiatric morbidity at the end of the study period; these were especially prevalent among health care workers. Another study of SARS patients observed chronic and persistent fatigue, myalgia, weakness, depression, and abnormal sleep patterns 1-3 years post infection (Moldofsky & Patcai, 2011).

Other Conditions

In a study by Wu et al. (2017), SARS survivors 12 years postinfection experienced metabolic disorders resulting from altered lipid metabolism, including hyperlipidemia and abnormal glucose metabolism. Significant differences were found in the level of metabolites between individuals that had been infected with SARS (Wu et al., 2017). Serum analyses identified disruption of levels of metabolomes, particularly phosphatidylinositol (PI) and lysophosphatidylinositol (LPI), two lipid metabolites, which could be due to high-dose steroid treatments used to treat the infection (Wu et al., 2017). SARS survivors also experienced lower quality of life 12 years after infection, as well as many different conditions, including tumors, cardiovascular disease, and increased susceptibility to infections (Wu et al., 2017). Epidemiologic studies have not found an association between SARS and leukemia or any effect on bone marrow cell proliferation (Li et al., 2007).

Autoimmune Conditions

Although many of the exact mechanisms are unknown, many studies have demonstrated an association between viral infections and the development of autoimmune conditions. Respiratory infections during early life have been associated with an increased risk of development of Type 1 diabetes in genetically predisposed children (Beyerlein et al., 2013). In a larger study, Lönnrot et al. (2017) reported that this risk of developing persistent islet autoimmunity increased with an increasing number of respiratory infections in early life. Furthermore, in a study of the effect of pandemic H1N1 on the development of diabetes, there was a twofold excess of incident diabetes in a subgroup with lab-confirmed H1N1, which could suggest that more severe infections may pose a greater risk in the development of autoimmunity (Ruiz et al. 2018). 

Among 39 follow-up SARSpatients, 6 had diabetes at the time of discharge and 2 still had diabetes after 3 years; acute diabetes appeared to be more prevalent than chronic diabetes (Yang et al., 2010). ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2 was found to be expressed in pancreatic islet cells, alveolar cells, myocardium of the heart, and parietal epithelial cells of the kidney, which is consistent with reports of multi-organ damage with SARS (Yang et al., 2010; Perrotta et al., 2020). This receptor is a homologue of ACE, a regulator of blood pressure, and has been implicated in hypertension, heart function, and diabetes (Yang et al., 2010).

The connection between viral infections and the development of autoimmunity has been studied with Epstein-Barr virus and cytomegalovirus. Epidemiologic studies have identified associations between Epstein-Barr and cytomegalovirus with systemic sclerosis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and systemic lupus erythematosus (Harley et al. 2018; Halenius & Hengel, 2014). These infections can trigger autoimmunity or are involved in exacerbations of autoimmunity through complex mechanisms, usually in genetically susceptible individuals (Sener & Afsar, 2012).

Conclusion

Previous long-term follow-up studies of severe respiratory infections suggest that a variety of symptoms may continue for months, or even years following infection. These symptoms, ranging from pulmonary fibrosis, chronic pain or fatigue, and even the development of autoimmunity have been shown to impair quality of life in those affected. With the lasting effect of these infections, it can be inferred that similar problems will be seen with infections of SARS-CoV-2.

Current Policy

Federal funding in the form of the Coronavirus Relief Fund and the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) has provided states and public and medical systems with support in their handling of the COVID-19 pandemic (HHS, 2020). Like with what was seen in China following SARS, the current pandemic will likely have many health policy implications. Public health surveillance is key in informing public health practice. COVID-19 is already a national notifiable condition, however, many of the possible long-term effects of the virus are not mandatory to report. States exercise the right to decide which conditions must be reported to state and local agencies (Roush et a., 1999). There are already COVID-19-related disease registries, including Caring for COVID-19 Transplant Patients and PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) (NIH, 2020).

Next Steps

Secure funding to follow-up on cases of COVID-19 longterm. In order to properly monitor cases over many years, funding is needed. Funding at the federal level would provide the necessary resources to provide for the following recommendations.

Create a national registry dedicated to long-term health outcomes of COVID-19. To collect information about chronic diseases following COVID-19 infections, a national registry would be beneficial. This voluntary registry would support medical and public health professionals, as well as researchers, in monitoring possible health outcomes as they appear and in tracking treatments. This registry should monitor the pulmonary, cardiovascular, neurological, psychiatric, and autoimmune effects, as well as any additional disorders that may arise.

Support healthcare systems in monitoring and treating the mental and physical effects in frontline healthcare workers. In addition to shortages of personal protection equipment, medical equipment, and staff, those working on the frontline must endure caring for severely ill patients, the fear of becoming infected with the virus, and many other circumstances that could lead to long-term psychological distress. Combined with the health effects of those that had COVID-19, healthcare workers are experiencing many occupational hazards that healthcare systems should monitor and provide services for when needed.

Begin long-term prospective research studies. The COVID19 pandemic has already proven to have a substantial effect on the world’s population. Those affected, particularly those with severe infections, should be properly monitored for any longterm effects. There is evidence to suggest that enrolling COVID19 patients in follow-up studies with pulmonary function tests and imaging may be informative. The many possible mental health side effects should also be monitored. These conditions may likely be more prevalent among health care workers. With what is known of the effect of viruses on the development of autoimmunity, large prospective studies of these effects could be done.

Study effects that were not monitored after previous pandemics. Generally, there have not been many studies on the development of chronic conditions following other pandemic respiratory viruses. Greater attention will likely be placed on the current pandemic and potential long-term effects should not be ignored. There is a need for further research on long-term cardiovascular effects and chronic lung disease. Few studies have been done on the risk for cancer following these infections.

Standardize treatments. Many studies conducted after the SARS outbreak called for the standardization of treatment to manage any long-term side effects of these treatments. Highdose steroid treatments used to treat SARS were associated with many issues, including femoral head osteonecrosis and chronic fatigue and sleep problems (Moldofsky & Patcai, 2011). Although steroid treatments for COVID-19 are not as prevalent, the long-term effects of all current treatments should be monitored.

Author

Emma Hymel is a Masters of Public Health student at the University of Alabama at Birmingham School of Public Health in the Department of Epidemiology. Any questions or commentary can be sent to: This email address is being protected from spambots. You need JavaScript enabled to view it.

Acknowledgements

The author would like to thank Dr. Suzanne Judd for her assistance in preparing this data brief.

The views and opinion expressed in this brief are those of the author and do not necessarily reflect the opinion of the UAB School of Public Health.

Suggestions for Further Reading

Perrotta, F., Matera, M. G., Cazzola, M., & Bianco, A. (2020). Severe respiratory SARS CoV2 infection: Does ACE2 receptor matter?. Respiratory Medicine, 168, 105996. https://doi.org/10.1016/j.rmed.2020.105996

Dasgupta, A., Kalhan, A., & Kalra, S. (2020). Long term complications and rehabilitation of COVID-19 patients. JPMA. The Journal of the Pakistan Medical Association, 70(Suppl 3)(5), S131–S135. https://doiorg.ezproxy3.lhl.uab.edu/10.5455/JPMA.32

Xie, M., & Chen, Q. (2020). Insight into 2019 novel coronavirus - An updated interim review and lessons from SARS-CoV and MERS-CoV. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 94, 119–124. https://doiorg.ezproxy3.lhl.uab.edu/10.1016/j.ijid.2020.03.

Sener, A. G., & Afsar, I. (2012). Infection and autoimmune disease. Rheumatology International, 32(11), 3331–3338. https://doi.org/10.1007/s00296-012-2451-z

References

Algahtani, H., Subahi, A., & Shirah, B. (2016). Neurological complications of middle east respiratory syndrome coronavirus: A report of two cases and review of the literature. Case Reports in Neurological Medicine, 2016, 3502683.

Beyerlein, A., Wehweck, F., Ziegler, A. G., & Pflueger, M. (2013). Respiratory infections in early life and the development of islet autoimmunity in children at increased type 1 diabetes risk: evidence from the BABYDIET study. JAMA Pediatrics, 167(9), 800–807.

Brown, S. M., Pittman, J., Miller Iii, R. R., Horton, K. D., Markewitz, B., Hirshberg, E., Jones, J., & Grissom, C. K. (2011). Right and left heart failure in severe H1N1 influenza A infection. The European Respiratory Journal, 37(1), 112–118.

Halenius, A., & Hengel, H. (2014). Human cytomegalovirus and autoimmune disease. BioMed Research International, 2014, 472978.

Harley, J. B., Chen, X., Pujato, M., Miller, D., Maddox, A., Forney, C., Magnusen, A. F., Lynch, A., Chetal, K., Yukawa, M., Barski, A., Salomonis, N., Kaufman, K. M., Kottyan, L. C., & Weirauch, M. T. (2018). Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nature Genetics, 50(5), 699–707.

Hui, D. S., Wong, K. T., Antonio, G. E., Tong, M., Chan, D. P., & Sung, J. J. (2009). Long-term sequelae of SARS: physical, neuropsychiatric, and quality-of-life assessment. Hong Kong Medical Journal = Xianggang yi xue za zhi, 15 Suppl 8, 21–23.

Li, C. K., Zee, B., Lee, J., Chik, K. W., Ha, S. Y., & Lee, V. (2007). Impact of SARS on development of childhood acute lymphoblastic leukaemia. Leukemia, 21(7), 1353–1356.

Liu, W., Peng, L., Liu, H., & Hua, S. (2015). Pulmonary function and clinical manifestations of patients infected with mild influenza A virus subtype H1N1: A one-year follow-up. PloS one, 10(7), e0133698.

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Perrotta, F., Matera, M. G., Cazzola, M., & Bianco, A. (2020). Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?. Respiratory Medicine, 168, 105996.

Roush, S., Birkhead, G., Koo, D., Cobb, A., & Fleming, D. (1999). Mandatory reporting of diseases and conditions by health care professionals and laboratories. JAMA, 282(2), 164-170.

Ruiz, P., Tapia, G., Bakken, I. J., Håberg, S. E., Hungnes, O., Gulseth, H. L., & Stene, L.C. (2018). Pandemic influenza and subsequent risk of type 1 diabetes: a nationwide cohort study. Diabetologia, 61(9), 1996–2004.

Sener, A. G., & Afsar, I. (2012). Infection and autoimmune disease. Rheumatology International, 32(11), 3331–3338. U.S. Department of Health and Human Services. (2020, June 02). HHS Provides an Additional $250 Million to Help U.S. Health Care Systems Respond to COVID-19. Retrieved July 22, 2020, from https://www.hhs.gov/about/news/2020/06/02/hhs-provides-additional250-million-help-us-health-care-systems-respond-covid-19.html.

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Yang, J. K., Lin, S. S., Ji, X. J., & Guo, L. M. (2010). Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetologica, 47(3), 193–199.

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