Differential Activation of Programmed Cell Death in Patients with Severe SARS-CoV-2 Infection Article Swipe
Ashligh Riegler
,
Paul Benson
,
Kenneth D. Long
,
Sixto M. Leal
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3059466/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3059466/v1
SARS-CoV-2 (SARS-2) causes severe lower airway disease and death in a subset of patients. Knowledge on the relative contribution of programmed cell death (PCD) to lung pathology is limited to few human autopsy studies with small sample size/scope, in vitro cell culture, and experimental model systems. In this study, we sought to identify, localize, and quantify activation of apoptosis, ferroptosis, pyroptosis, and necroptosis in FFPE lung tissues from patients that died from severe SARS-2 infection (n=28) relative to uninfected controls (n=13). Immunofluorescence (IF) staining, whole-slide imaging, and Image J software was used to localize and quantify expression of SARS-2 nucleoprotein and the following PCD protein markers: cleaved Caspase-3, pMLKL, cleaved Gasdermin D, and CD71, respectively. IF showed differential activation of each PCD pathway in SARS-2 infected lungs and dichotomous staining for SARS-2 nucleoprotein enabling distinction between high (n=9) vs low viral burden (n= 19). No differences were observed in apoptosis and ferroptosis in SARS-2 infected lungs relative to uninfected controls. However, both pyroptosis and necroptosis were significantly increased in SARS-2 infected lungs. Increased pyroptosis was observed in SARS-2 infected lungs, irrespective of viral burden, suggesting an inflammation-driven mechanism. In contrast, necroptosis exhibited a very strong positive correlation with viral burden (R2=0.9925), suggesting a direct SARS-2 mediated effect. These data indicate a possible novel mechanism for viral-mediated necroptosis and a potential role for both lytic programmed cell death pathways, necroptosis and pyroptosis, in mediating infection outcome.
Related Topics
Concepts
Necroptosis
Pyroptosis
Programmed cell death
Apoptosis
Biology
AIM2
Immunology
Virology
Inflammation
Inflammasome
Biochemistry
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3059466/v1
- https://www.researchsquare.com/article/rs-3059466/latest.pdf
- OA Status
- green
- Cited By
- 2
- References
- 82
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4382197730
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4382197730Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3059466/v1Digital Object Identifier
- Title
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Differential Activation of Programmed Cell Death in Patients with Severe SARS-CoV-2 InfectionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-06-27Full publication date if available
- Authors
-
Ashligh Riegler, Paul Benson, Kenneth D. Long, Sixto M. LealList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-3059466/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3059466/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-3059466/latest.pdfDirect OA link when available
- Concepts
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Necroptosis, Pyroptosis, Programmed cell death, Apoptosis, Biology, AIM2, Immunology, Virology, Inflammation, Inflammasome, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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82Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W3003217347, https://openalex.org/W3009912996, https://openalex.org/W3127420938, https://openalex.org/W3165479483, https://openalex.org/W4205129832, https://openalex.org/W4207080708, https://openalex.org/W3205662191, https://openalex.org/W4205944693, https://openalex.org/W4205970115, https://openalex.org/W3135019488, https://openalex.org/W6787532220, https://openalex.org/W3134078202, https://openalex.org/W3087274635, https://openalex.org/W3168768836, https://openalex.org/W6754814001, https://openalex.org/W6779756488, https://openalex.org/W3118873013, https://openalex.org/W6791513857, https://openalex.org/W3185624356, https://openalex.org/W3203016970, https://openalex.org/W6776583185, https://openalex.org/W3016538467, https://openalex.org/W3042427532, https://openalex.org/W4282984390, https://openalex.org/W3088808621, https://openalex.org/W3086155175, https://openalex.org/W4281642119, https://openalex.org/W4323565685, https://openalex.org/W3092245820, https://openalex.org/W4210866043, https://openalex.org/W3033966010, https://openalex.org/W4225340317, https://openalex.org/W4226413268, https://openalex.org/W4318705692, https://openalex.org/W3046768549, https://openalex.org/W2916224930, https://openalex.org/W4286513839, https://openalex.org/W4284703904, https://openalex.org/W2889848040, https://openalex.org/W4323067152, https://openalex.org/W2799493433, https://openalex.org/W3007474161, https://openalex.org/W3186709926, https://openalex.org/W4220909825, https://openalex.org/W3200053343, https://openalex.org/W2049537492, https://openalex.org/W4317717850, https://openalex.org/W3099019571, https://openalex.org/W3195205912, https://openalex.org/W4221000296, https://openalex.org/W3136955306, https://openalex.org/W3046661760, https://openalex.org/W2139552156, https://openalex.org/W4282575739, https://openalex.org/W3081487801, https://openalex.org/W3159095745, https://openalex.org/W3015772943, https://openalex.org/W2560541542, https://openalex.org/W3036178624, https://openalex.org/W2892710900, https://openalex.org/W3164928292, https://openalex.org/W3158998799, https://openalex.org/W3008452791, https://openalex.org/W4318984320, https://openalex.org/W3018507926, https://openalex.org/W2968612009, https://openalex.org/W4241088937, https://openalex.org/W2008757142, https://openalex.org/W3098914336, https://openalex.org/W3059375228, https://openalex.org/W4226136174, https://openalex.org/W2078399145, https://openalex.org/W3109063130, https://openalex.org/W3208880459, https://openalex.org/W2937346106, https://openalex.org/W4220895238, https://openalex.org/W4225975018, https://openalex.org/W2977568416, https://openalex.org/W3189821197, https://openalex.org/W4288033466, https://openalex.org/W3012782412, https://openalex.org/W3198428298 |
| referenced_works_count | 82 |
| abstract_inverted_index.J | 89 |
| abstract_inverted_index.a | 11, 193, 203, 211, 219 |
| abstract_inverted_index.D, | 112 |
| abstract_inverted_index.IF | 116 |
| abstract_inverted_index.In | 47, 189 |
| abstract_inverted_index.No | 145 |
| abstract_inverted_index.an | 186 |
| abstract_inverted_index.in | 10, 39, 64, 124, 149, 153, 169, 177, 232 |
| abstract_inverted_index.is | 28 |
| abstract_inverted_index.of | 13, 20, 58, 98, 120, 182 |
| abstract_inverted_index.on | 16 |
| abstract_inverted_index.to | 25, 30, 52, 78, 93, 158 |
| abstract_inverted_index.vs | 139 |
| abstract_inverted_index.we | 50 |
| abstract_inverted_index.(n= | 143 |
| abstract_inverted_index.PCD | 104, 122 |
| abstract_inverted_index.and | 8, 43, 55, 62, 87, 95, 101, 113, 128, 151, 164, 218, 230 |
| abstract_inverted_index.few | 31 |
| abstract_inverted_index.for | 131, 215, 222 |
| abstract_inverted_index.low | 140 |
| abstract_inverted_index.the | 17, 102 |
| abstract_inverted_index.was | 91, 175 |
| abstract_inverted_index.(IF) | 83 |
| abstract_inverted_index.19). | 144 |
| abstract_inverted_index.FFPE | 65 |
| abstract_inverted_index.both | 162, 223 |
| abstract_inverted_index.cell | 22, 41, 226 |
| abstract_inverted_index.data | 209 |
| abstract_inverted_index.died | 71 |
| abstract_inverted_index.each | 121 |
| abstract_inverted_index.from | 68, 72 |
| abstract_inverted_index.high | 137 |
| abstract_inverted_index.lung | 26, 66 |
| abstract_inverted_index.role | 221 |
| abstract_inverted_index.that | 70 |
| abstract_inverted_index.this | 48 |
| abstract_inverted_index.used | 92 |
| abstract_inverted_index.very | 194 |
| abstract_inverted_index.were | 147, 166 |
| abstract_inverted_index.with | 35, 198 |
| abstract_inverted_index.(PCD) | 24 |
| abstract_inverted_index.(n=9) | 138 |
| abstract_inverted_index.CD71, | 114 |
| abstract_inverted_index.Image | 88 |
| abstract_inverted_index.These | 208 |
| abstract_inverted_index.death | 9, 23, 227 |
| abstract_inverted_index.human | 32 |
| abstract_inverted_index.lower | 5 |
| abstract_inverted_index.lungs | 127, 156 |
| abstract_inverted_index.lytic | 224 |
| abstract_inverted_index.model | 45 |
| abstract_inverted_index.novel | 213 |
| abstract_inverted_index.small | 36 |
| abstract_inverted_index.viral | 141, 183, 199 |
| abstract_inverted_index.vitro | 40 |
| abstract_inverted_index.(n=28) | 76 |
| abstract_inverted_index.SARS-2 | 74, 99, 125, 132, 154, 170, 178, 205 |
| abstract_inverted_index.airway | 6 |
| abstract_inverted_index.burden | 142, 200 |
| abstract_inverted_index.causes | 3 |
| abstract_inverted_index.direct | 204 |
| abstract_inverted_index.lungs, | 180 |
| abstract_inverted_index.lungs. | 172 |
| abstract_inverted_index.pMLKL, | 109 |
| abstract_inverted_index.sample | 37 |
| abstract_inverted_index.severe | 4, 73 |
| abstract_inverted_index.showed | 117 |
| abstract_inverted_index.sought | 51 |
| abstract_inverted_index.strong | 195 |
| abstract_inverted_index.study, | 49 |
| abstract_inverted_index.subset | 12 |
| abstract_inverted_index.(n=13). | 81 |
| abstract_inverted_index.autopsy | 33 |
| abstract_inverted_index.between | 136 |
| abstract_inverted_index.burden, | 184 |
| abstract_inverted_index.cleaved | 107, 110 |
| abstract_inverted_index.disease | 7 |
| abstract_inverted_index.effect. | 207 |
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| abstract_inverted_index.pathway | 123 |
| abstract_inverted_index.protein | 105 |
| abstract_inverted_index.studies | 34 |
| abstract_inverted_index.tissues | 67 |
| abstract_inverted_index.(SARS-2) | 2 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.However, | 161 |
| abstract_inverted_index.controls | 80 |
| abstract_inverted_index.culture, | 42 |
| abstract_inverted_index.enabling | 134 |
| abstract_inverted_index.imaging, | 86 |
| abstract_inverted_index.indicate | 210 |
| abstract_inverted_index.infected | 126, 155, 171, 179 |
| abstract_inverted_index.localize | 94 |
| abstract_inverted_index.markers: | 106 |
| abstract_inverted_index.mediated | 206 |
| abstract_inverted_index.observed | 148, 176 |
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| abstract_inverted_index.possible | 212 |
| abstract_inverted_index.quantify | 56, 96 |
| abstract_inverted_index.relative | 18, 77, 157 |
| abstract_inverted_index.software | 90 |
| abstract_inverted_index.staining | 130 |
| abstract_inverted_index.systems. | 46 |
| abstract_inverted_index.Gasdermin | 111 |
| abstract_inverted_index.Increased | 173 |
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| abstract_inverted_index.contrast, | 190 |
| abstract_inverted_index.controls. | 160 |
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| abstract_inverted_index.pathways, | 228 |
| abstract_inverted_index.patients. | 14 |
| abstract_inverted_index.potential | 220 |
| abstract_inverted_index.staining, | 84 |
| abstract_inverted_index.Caspase-3, | 108 |
| abstract_inverted_index.SARS-CoV-2 | 1 |
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| abstract_inverted_index.apoptosis, | 59 |
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| abstract_inverted_index.suggesting | 185, 202 |
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| abstract_inverted_index.dichotomous | 129 |
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| abstract_inverted_index.distinction | 135 |
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| abstract_inverted_index.pyroptosis, | 61, 231 |
| abstract_inverted_index.size/scope, | 38 |
| abstract_inverted_index.whole-slide | 85 |
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| abstract_inverted_index.respectively. | 115 |
| abstract_inverted_index.significantly | 167 |
| abstract_inverted_index.viral-mediated | 216 |
| abstract_inverted_index.Immunofluorescence | 82 |
| abstract_inverted_index.inflammation-driven | 187 |
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| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5045967076 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 4 |
| corresponding_institution_ids | https://openalex.org/I32389192 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8500000238418579 |
| sustainable_development_goals[0].display_name | Good health and well-being |
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| citation_normalized_percentile.is_in_top_10_percent | False |