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JHLT: COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal

sharon sanders

Editor-in-Chief & President
COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal

Hasan K. Siddiqi, MD, MSCR
,
Mandeep R. Mehra, MD, MSc[SUP]
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[/SUP][SUP],[/SUP]Correspondence information about the author MD, MSc Mandeep R. MehraEmail the author MD, MSc Mandeep R. Mehra
Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal
DOI: https://doi.org/10.1016/j.healun.2020.03.012

Article Info
The onslaught of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) has gripped the world in a pandemic and challenged the culture, economy and healthcare infrastructure of its population. It has become increasingly important that health systems and their clinicians adopt a universal consolidated framework to recognize the staged progression of COVID-19 illness in order to deploy and investigate targeted therapy likely to save lives. The largest report of COVID-19 from the Chinese Centers for Disease Control and Prevention summarized findings from 72, 314 cases and noted that while 81% were of a mild nature with an overall case fatality rate of 2.3%, a small sub-group of 5% presented with respiratory failure, septic shock and multi-organ dysfunction resulting in fatality in half of such cases, a finding that suggests that it is within this group that the opportunity for life saving measures may be most pertinent.

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Stage III (severe) – Systemic Hyperinflammation


A minority of COVID-19 patients will transition into the third and most severe stage of illness, which manifests as an extra-pulmonary systemic hyperinflammation syndrome. In this stage, markers of systemic inflammation appear to be elevated. COVID-19 infection results in a decrease in helper, suppressor and regulatory T cell counts.[SUP]9[/SUP] Studies have shown that inflammatory cytokines and biomarkers such as interleukin (IL)-2, IL-6, IL-7, granulocyte-colony stimulating factor, macrophage inflammatory protein 1-α, tumor necrosis factor-α, C-reactive protein, ferritin, and D-dimer are significantly elevated in those patients with more severe disease.[SUP]10[/SUP] Troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) can also be elevated. A form akin to hemophagocytic lymphohistiocytosis (sHLH) may occur in patients in this advanced stage of disease.[SUP]11[/SUP] In this stage, shock, vasoplegia, respiratory failure and even cardiopulmonary collapse are discernable. Systemic organ involvement, even myocarditis, would manifest during this stage.

Tailored therapy in stage III hinges on the use of immunomodulatory agents to reduce systemic inflammation before it overwhelmingly results in multi-organ dysfunction. In this phase, use of corticosteroids may be justified in concert with the use of cytokine inhibitors such as tocilizumab (IL-6 inhibitor) or anakinra (IL-1 receptor antagonist).[SUP]11[/SUP] Intravenous immune globulin (IVIG) may also play a role in modulating an immune system that is in a hyperinflammatory state. Overall, the prognosis and recovery from this critical stage of illness is poor, and rapid recognition and deployment of such therapy may have the greatest yield.

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https://www.jhltonline.org/article/S...473-X/abstract
 
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