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ACEP COVID-19 Field Guide

Table of Contents

Immunocompromised Patients

Special Populations

Authors: Christopher Payette, MD; and Aisha T. Terry, MD, MPH, FACEP

Data from China assert that elderly patients suffer from more severe cases of COVID-19. Given that aging is associated with a declining immune response, it may be plausible that all immunocompromised individuals carry higher risk relative to COVID-19. Many patients who regularly interact with the health care system and emergency department are immunocompromised. The CDC has identified immunocompromised patients as being at high risk of severe disease due to COVID-19. This group includes patients with cancer, HIV/AIDS, malnutrition, and other primary immunodeficiency disorders. It also encompasses those who are taking medications that suppress the immune system, which includes transplant patients and chronic steroid users. 

The pathophysiology of COVID-19 infection involves the angiotensin-converting enzyme 2 as the host cell-surface receptor. This receptor is expressed by cells in the blood vessels, heart, kidneys, GI tract, and lung alveolar epithelial cells. COVID-19 case reports describe an infection that can target the lungs, heart, GI tract, and CNS. In infected patients, cytokine release syndrome has been described with upregulation of proinflammatory cytokines and chemokines. Ultimately, this “cytokine storm” creates a hyperinflammatory syndrome, leading to multiorgan failure in infected patients. It appears that the primary driver of lung tissue damage, and ultimately the progression to a syndrome that some theorize is similar to acute respiratory distress syndrome (ARDS), is based on the activation of the host’s immune system. Another hypothesis around the pathophysiology of COVID-19 is that it results in a hemoglobinopathy that decreases oxygen carrying capacity and behaves in a manner similar to altitude sickness.

Patients taking corticosteroids

While studies have shown that over time low-dose corticosteroids do not seem to affect the incidence of serious infections in patients, there is concern for a dose-dependent relationship that may affect patients taking higher doses. Although there is a concern for increased risk of viral infections in patients on corticosteroids, there are also theories about potential corticosteroid benefit in patients with viral illnesses. While corticosteroids may blunt or inhibit the immune response, the pathogenesis of lung damage associated with COVID-19 appears to be host inflammatory-response mediated, which suggests that tissue damage may be decreased by corticosteroid use. While some patients with MERS-CoV and SARS-CoV were treated with corticosteroids, however, the literature suggests an overall negative effect of corticosteroids in managing these particular viral infections. A recent meta-analysis reviewed the use of corticosteroids to treat influenza and found an association with increased mortality, an increased rate of secondary infection, and longer lengths of stay in the ICU. With regard to ARDS, there is insufficient evidence to suggest corticosteroids as a treatment. Therefore, in conjunction with WHO guidance, the use of corticosteroids should be avoided in COVID-19 patients unless there is another existing indication. 

Patients on immune-suppressing or immune-modulating therapy

The literature suggests that patients on immune-suppressing therapies may not actually be at increased risk for severe respiratory disease with COVID-19. Unlike other viral agents such as adenovirus, rhinovirus, norovirus, and influenza, coronavirus has not been shown to cause more severe disease in immunosuppressed patients. This is because the patient’s immune response drives the injury of lung tissue during infection, possibly leading to an ARDS-like syndrome. Other reports of patients on immune-modulating therapy describe significant clinical symptoms, such as GI symptoms and fever with associated respiratory symptoms developing with time. These reports suggest that immunosuppressed patients may require closer follow-up care over time. 

Oncologic patients

Cancer patients may be immunocompromised secondary to their underlying malignancy or due to anticancer therapy and are, therefore, at an increased risk of developing infections. This risk of infection is compounded by their frequent visits to the hospital or infusion centers to receive treatment and evaluation. As a result, cancer patients appear to have a twofold increased risk of contracting COVID-19 in comparison to the general population. Currently, there are no guidelines by the WHO or CDC regarding treatment specific to cancer patients with COVID-19. With regard to emergency department care, there should be an emphasis on strict and safe triaging of these patients in order to ensure appropriate precautionary room assignment and to determine disposition relative to hospitalization versus discharge expeditiously. Overall, minimizing their exposure to patients with COVID-19 should be a goal, with an avoidance of placing these patients in grouped COVID-19 areas, particularly prior to having their test results confirmed. 

HIV/AIDS

While there are case reports of patients with HIV and COVID-19 coinfection, the effect of host immune status in COVID-19 is unknown. One case report suggests that HIV-induced immune dysfunction may affect immune response to COVID-19 and, ultimately, viral clearance. While the impact of HIV on the management of COVID-19 is still unclear, it is clear that COVID-19 has affected access to the HIV care continuum, which could negatively affect the disease course of HIV. With significant disruption in the way routine care is delivered during the COVID-19 pandemic, it will be most important for governments, community organizations, and international groups to partner together to maintain the HIV care continuum through telehealth innovations and optimal communication to ensure minimal disruption of routine HIV services. 

Quarantining recommendations

The CDC has delineated a test-based strategy for discontinuing home isolation for immunocompromised patients with COVID-19. They recommend that these patients maintain isolation until:

  1. Resolution of fever, without the use of antipyretics;
  2. Improvement in respiratory symptoms, including cough and shortness of breath; and
  3. Negative results of an FDA Emergency Use Authorized molecular assay for COVID-19 from at least two consecutive nasopharyngeal swab specimens collected at least 24 hours apart.

This aligns with recommendations based on case reports, which conclude that while these patients do not require significant differential treatment, they do warrant close follow-up care and close consideration for potential complications. 

Summary

While knowledge about COVID-19 in immunocompromised patients is evolving and there is still much unknown, the CDC currently recommends that immunocompromised patients undergo similar evaluation and treatment compared to nonimmunocompromised patients. However, there should be higher suspicion for complications, and closer follow-up care is a plausible approach. WHO does not currently recommend the use of corticosteroids in COVID-19–positive patients. It is unclear as to how the chronic use of immune-suppressing and immune-modulating therapies in patients who become infected with COVID-19 affects outcomes, but some reports suggest protection against severe complications. 

References

  1. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). CDC website. 2020 Apr 6. 
  2. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271‐280.e8. doi:10.1016/j.cell.2020.02.052
  3. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv website. 2020 Jan 26.
  4. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19 [published online ahead of print, 2020 Mar 5]. J Pharm Anal. 2020. doi:10.1016/j.jpha.2020.03.001
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  7. Wan S, Yi Q, Fan S, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv website. 2020 Feb 12.
  8. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034. doi:10.1016/S0140-6736(20)30628-0
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  10. Strehl C, Ehlers L, Gaber T, Buttgereit F. Glucocorticoids-all-rounders tackling the versatile players of the immune system. Front Immunol. 2019;10:1744. Published 2019 Jul 24. doi:10.3389/fimmu.2019.01744
  11. D'Antiga L. Coronaviruses and immunosuppressed patients: the facts during the third epidemic [published online ahead of print, 2020 Mar 20]. Liver Transpl. 2020;10.1002/lt.25756. doi:10.1002/lt.25756
  12. Al‐Shamsi HO, Alhazzani W, Alhuraiji A, et al. A practical approach to the management of cancer patients during the novel coronavirus disease 2019 (COVID‐19) pandemic: an international collaborative group [published online ahead of print, 2020 Apr 3]. Oncologist. 2020;10.1634/theoncologist.2020-0213. doi:10.1634/theoncologist.2020-0213
  13. Zhao J, Liao X, Wang H, et al. Early virus clearance and delayed antibody response in a case of COVID-19 with a history of co-infection with HIV-1 and HCV [published online ahead of print, 2020 Apr 9]. Clin Infect Dis. 2020;ciaa408. doi:10.1093/cid/ciaa408
  14. Jiang H, Zhou Y, Tang W. Maintaining HIV care during the COVID-19 pandemic [published online ahead of print, 2020 Apr 6]. Lancet HIV. 2020;S2352-3018(20)30105-3. doi:10.1016/S2352-3018(20)30105-3
  15. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Ending home isolation for immunocompromised persons with COVID-19. CDC website. Reviewed 2020 Mar 16.

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