Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illness Article Swipe
Eric D. Morrell
,
Pavan K. Bhatraju
,
Neha A. Sathe
,
J. Lawson
,
L. Mabrey
,
Sarah E. Holton
,
Scott Presnell
,
Alice Wiedeman
,
Carolina Acosta‐Vega
,
Mallorie A. Mitchem
,
Ted Liu
,
Xin-Ya Chai
,
Sharon K. Sahi
,
Carolyn Brager
,
Marika Orlov
,
Sana Sakr
,
Anthony Sader
,
Dawn M. Lum
,
Neall Koetje
,
A. Garay
,
Elizabeth Barnes
,
Gail Cromer
,
Mary K. Bray
,
Sudhakar Pipavath
,
Susan L. Fink
,
Laura Evans
,
S. Alice Long
,
T. Eoin West
,
Mark M. Wurfel
,
Carmen Mikacenic
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00049.2022
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00049.2022
Critically ill patients manifest many of the same immune features seen in coronavirus disease 2019 (COVID-19), including both “cytokine storm” and “immune suppression.” However, direct comparisons of molecular and cellular profiles between contemporaneously enrolled critically ill patients with and without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited. We sought to identify immune signatures specifically enriched in critically ill patients with COVID-19 compared with patients without COVID-19. We enrolled a multisite prospective cohort of patients admitted under suspicion for COVID-19, who were then determined to be SARS-CoV-2-positive ( n = 204) or -negative ( n = 122). SARS-CoV-2-positive patients had higher plasma levels of CXCL10, sPD-L1, IFN-γ, CCL26, C-reactive protein (CRP), and TNF-α relative to SARS-CoV-2-negative patients adjusting for demographics and severity of illness (Bonferroni P value < 0.05). In contrast, the levels of IL-6, IL-8, IL-10, and IL-17A were not significantly different between the two groups. In SARS-CoV-2-positive patients, higher plasma levels of sPD-L1 and TNF-α were associated with fewer ventilator-free days (VFDs) and higher mortality rates (Bonferroni P value < 0.05). Lymphocyte chemoattractants such as CCL17 were associated with more severe respiratory failure in SARS-CoV-2-positive patients, but less severe respiratory failure in SARS-CoV-2-negative patients ( P value for interaction < 0.01). Circulating T cells and monocytes from SARS-CoV-2-positive subjects were hyporesponsive to in vitro stimulation compared with SARS-CoV-2-negative subjects. Critically ill SARS-CoV-2-positive patients exhibit an immune signature of high interferon-induced lymphocyte chemoattractants (e.g., CXCL10 and CCL17) and immune cell hyporesponsiveness when directly compared with SARS-CoV-2-negative patients. This suggests a specific role for T-cell migration coupled with an immune-checkpoint regulatory response in COVID-19-related critical illness.
Related Topics
Concepts
Immune system
Immunology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Chemokine
Critical illness
Coronavirus disease 2019 (COVID-19)
2019-20 coronavirus outbreak
Virology
Medicine
Disease
Critically ill
Pathology
Intensive care medicine
Infectious disease (medical specialty)
Outbreak
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1152/ajplung.00049.2022
- OA Status
- green
- Cited By
- 25
- References
- 79
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4282940772
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4282940772Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1152/ajplung.00049.2022Digital Object Identifier
- Title
-
Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illnessWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-05-24Full publication date if available
- Authors
-
Eric D. Morrell, Pavan K. Bhatraju, Neha A. Sathe, J. Lawson, L. Mabrey, Sarah E. Holton, Scott Presnell, Alice Wiedeman, Carolina Acosta‐Vega, Mallorie A. Mitchem, Ted Liu, Xin-Ya Chai, Sharon K. Sahi, Carolyn Brager, Marika Orlov, Sana Sakr, Anthony Sader, Dawn M. Lum, Neall Koetje, A. Garay, Elizabeth Barnes, Gail Cromer, Mary K. Bray, Sudhakar Pipavath, Susan L. Fink, Laura Evans, S. Alice Long, T. Eoin West, Mark M. Wurfel, Carmen MikacenicList of authors in order
- Landing page
-
https://doi.org/10.1152/ajplung.00049.2022Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/9208434Direct OA link when available
- Concepts
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Immune system, Immunology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Chemokine, Critical illness, Coronavirus disease 2019 (COVID-19), 2019-20 coronavirus outbreak, Virology, Medicine, Disease, Critically ill, Pathology, Intensive care medicine, Infectious disease (medical specialty), OutbreakTop concepts (fields/topics) attached by OpenAlex
- Cited by
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25Total citation count in OpenAlex
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2025: 2, 2024: 8, 2023: 11, 2022: 4Per-year citation counts (last 5 years)
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79Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.immune | 8, 52, 227, 239 |
| abstract_inverted_index.levels | 102, 132, 152 |
| abstract_inverted_index.plasma | 101, 151 |
| abstract_inverted_index.sPD-L1 | 154 |
| abstract_inverted_index.severe | 40, 182, 190 |
| abstract_inverted_index.sought | 49 |
| abstract_inverted_index.CXCL10, | 104 |
| abstract_inverted_index.IFN-γ, | 106 |
| abstract_inverted_index.between | 31, 143 |
| abstract_inverted_index.coupled | 256 |
| abstract_inverted_index.disease | 13 |
| abstract_inverted_index.exhibit | 225 |
| abstract_inverted_index.failure | 184, 192 |
| abstract_inverted_index.groups. | 146 |
| abstract_inverted_index.illness | 123 |
| abstract_inverted_index.protein | 109 |
| abstract_inverted_index.sPD-L1, | 105 |
| abstract_inverted_index.without | 39, 65 |
| abstract_inverted_index.COVID-19 | 61 |
| abstract_inverted_index.However, | 23 |
| abstract_inverted_index.admitted | 75 |
| abstract_inverted_index.cellular | 29 |
| abstract_inverted_index.compared | 62, 217, 244 |
| abstract_inverted_index.critical | 264 |
| abstract_inverted_index.directly | 243 |
| abstract_inverted_index.enriched | 55 |
| abstract_inverted_index.enrolled | 33, 68 |
| abstract_inverted_index.features | 9 |
| abstract_inverted_index.identify | 51 |
| abstract_inverted_index.illness. | 265 |
| abstract_inverted_index.limited. | 47 |
| abstract_inverted_index.manifest | 3 |
| abstract_inverted_index.patients | 2, 36, 59, 64, 74, 98, 116, 195, 224 |
| abstract_inverted_index.profiles | 30 |
| abstract_inverted_index.relative | 113 |
| abstract_inverted_index.response | 261 |
| abstract_inverted_index.severity | 121 |
| abstract_inverted_index.specific | 251 |
| abstract_inverted_index.storm” | 19 |
| abstract_inverted_index.subjects | 210 |
| abstract_inverted_index.suggests | 249 |
| abstract_inverted_index.syndrome | 43 |
| abstract_inverted_index.-negative | 92 |
| abstract_inverted_index.COVID-19, | 79 |
| abstract_inverted_index.COVID-19. | 66 |
| abstract_inverted_index.adjusting | 117 |
| abstract_inverted_index.contrast, | 130 |
| abstract_inverted_index.different | 142 |
| abstract_inverted_index.including | 16 |
| abstract_inverted_index.migration | 255 |
| abstract_inverted_index.molecular | 27 |
| abstract_inverted_index.monocytes | 207 |
| abstract_inverted_index.mortality | 166 |
| abstract_inverted_index.multisite | 70 |
| abstract_inverted_index.patients, | 149, 187 |
| abstract_inverted_index.patients. | 247 |
| abstract_inverted_index.signature | 228 |
| abstract_inverted_index.subjects. | 220 |
| abstract_inverted_index.suspicion | 77 |
| abstract_inverted_index.“immune | 21 |
| abstract_inverted_index.C-reactive | 108 |
| abstract_inverted_index.Critically | 0, 221 |
| abstract_inverted_index.Lymphocyte | 173 |
| abstract_inverted_index.associated | 158, 179 |
| abstract_inverted_index.critically | 34, 57 |
| abstract_inverted_index.determined | 83 |
| abstract_inverted_index.lymphocyte | 232 |
| abstract_inverted_index.regulatory | 260 |
| abstract_inverted_index.signatures | 53 |
| abstract_inverted_index.(Bonferroni | 124, 168 |
| abstract_inverted_index.(COVID-19), | 15 |
| abstract_inverted_index.Circulating | 203 |
| abstract_inverted_index.comparisons | 25 |
| abstract_inverted_index.coronavirus | 12 |
| abstract_inverted_index.interaction | 200 |
| abstract_inverted_index.prospective | 71 |
| abstract_inverted_index.respiratory | 42, 183, 191 |
| abstract_inverted_index.stimulation | 216 |
| abstract_inverted_index.“cytokine | 18 |
| abstract_inverted_index.(SARS-CoV-2) | 45 |
| abstract_inverted_index.demographics | 119 |
| abstract_inverted_index.specifically | 54 |
| abstract_inverted_index.coronavirus-2 | 44 |
| abstract_inverted_index.significantly | 141 |
| abstract_inverted_index.hyporesponsive | 212 |
| abstract_inverted_index.suppression.” | 22 |
| abstract_inverted_index.ventilator-free | 161 |
| abstract_inverted_index.COVID-19-related | 263 |
| abstract_inverted_index.chemoattractants | 174, 233 |
| abstract_inverted_index.contemporaneously | 32 |
| abstract_inverted_index.immune-checkpoint | 259 |
| abstract_inverted_index.hyporesponsiveness | 241 |
| abstract_inverted_index.interferon-induced | 231 |
| abstract_inverted_index.SARS-CoV-2-negative | 115, 194, 219, 246 |
| abstract_inverted_index.SARS-CoV-2-positive | 86, 97, 148, 186, 209, 223 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 95 |
| corresponding_author_ids | https://openalex.org/A5076303643 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 30 |
| corresponding_institution_ids | https://openalex.org/I4391012615 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8899999856948853 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.9174746 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |