Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

By E. Giamarellos‐Bourboulis, Mihai G. Netea, N. Rovina, K. Akinosoglou, A. Antoniadou, N. Antonakos, G. Damoraki, T. Gkavogianni, M. Adami, P. Katsaounou and 18 more. Cell Host and Microbe, 2020

1,950 citations recorded by the source corpus.

Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.

Subfields: Infectious Diseases, Neurology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/2c6ba8d8d1f583c2366f7f5f9e840aa55275cf7d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. A. Aschenbrenner
2. Alessandro Sette
3. Shane Crotty
4. E. Wherry
5. F. Krammer
6. J. Ziebuhr

In Neurology

1. A. Aschenbrenner
2. Shane Crotty
3. Florent Ginhoux

Citations in the corpus

• Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19 (2020, positive): “, 2009), expression of HLA-DR on CD14High circulating monocytes is low in severe COVID-19, which correlates with, and could be mediated by, IL-6 overproduction (Giamarellos-Bourboulis et al., 2020).”
• Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications (2020, result): “Together, these data indicate that T cell activation in COVID-19 patients is similar to what has been observed in other acute infections or vaccinations (37, 39, 40) and identify patients with high, low, or essentially no T cell response on the basis of KI67 or CD38HLA-DR expression compared with co”
• Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals (2020, positive): “Critical (ICU) and fatal COVID-19 (and SARS) outcomes are associated with elevated levels of inflammatory cytokines and chemokines, including interleukin-6 (IL-6) (Giamarellos-Bourboulis et al., 2020; Wong et al., 2004; Zhou et al., 2020) Vaccine development against acute viral infections classicall”
• Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, positive): “have come to the conclusion that two patterns of immune dysfunction exist in worsening COVID-19: (i) one pattern highly suggestive of macrophage activation syndrome (hyperferritinemia and elevated H score : 25% of patients), which is driven by IL-1β; and (ii) one pattern with immune dysregulation dr”
• Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment (2020, positive): “Patients with severe COVID-19 have high systemic levels of inflammatory cytokines, particularly interleukin (IL)-6 and IL-1b (Chen et al., 2020; Giamarellos-Bourboulis et al., 2020; Lucas et al., 2020;Onget al., 2020),whereas interferon (IFN) responses appear blunted, as shown by whole blood transcr”