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A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce.
Laudanski, Krzysztof; Okeke, Tony; Siddiq, Kumal; Hajj, Jihane; Restrepo, Mariana; Gullipalli, Damodar; Song, Wen-Chao.
  • Laudanski K; Department of Anesthesiology and Critical Care, The University of Pennsylvania, JMB 127, 3620 Hamilton Walk, Philadelphia, PA, 19146, USA. klaudanski@gmail.com.
  • Okeke T; Leonard Davis Institute for Health Economics, The University of Pennsylvania Colonial Penn Center, 3641 Locust Walk, Philadelphia, PA, 19104, USA. klaudanski@gmail.com.
  • Siddiq K; School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA.
  • Hajj J; College of Arts and Sciences, Drexel University, Philadelphia, PA, USA.
  • Restrepo M; School of Nursing, Widener College, Chester, PA, USA.
  • Gullipalli D; College of Arts and Sciences, The University of Pennsylvania, Philadelphia, PA, USA.
  • Song WC; Department of Systems Pharmacology and Translational Therapeutics, The University of Pennsylvania, Philadelphia, PA, USA.
Sci Rep ; 12(1): 13658, 2022 08 11.
Article in English | MEDLINE | ID: covidwho-1991658
ABSTRACT
A complement effect on homeostasis during infection is determined by both cytotoxic (activate complement component 5 (C5a) terminal cytotoxic complex (TCC)), and cytoprotective elements (complement factor H (FH), as well as apolipoprotein E (ApoE)). Here, we investigated the gap in knowledge in their blood milieu during SARS-CoV-2 infection with respect to the viral burden, level of tissue necrosis, and immunological response. 101 patients hospitalized with a PCR-confirmed diagnosis of COVID-19 had blood collected at H1 (48 h), H2 (3-4 Days), H3 (5-7 days), H4 (more than 7 days up to 93 days). Pre-existing conditions, treatment, the incidence of cerebrovascular events (CVA), a history of deep venous thrombosis (DVT) and pulmonary embolism (PE), and mortality was collected using electronic medical records. Plasma C5a, TCC, FH, and ApoE were considered as a complement milieu. Tissue necrosis (HMGB1, RAGE), non-specific inflammatory responses (IL-6, C-reactive protein), overall viral burden (SARS-CoV-2 spike protein), and specific immune responses (IgG, IgA, IgM directed αS- & N-proteins) were assessed simultaneously. C5a remained elevated across all time points, with the peak at 5-7 days. Studied elements of complement coalesced around three clusters #0 (↑↑↑C5a, ↑↑TCC, ↓↓ApoE), #1 ↑C5a, ↑TCC, ↑↑↑FH); #2 (↑C5a, ↑TCC, ↑FH, ↑↑↑ApoE). The decline in FH and ApoE was a predictor of death, while TCC and C5a correlated with patient length of stay, APACHE, and CRP. Increased levels of C5a (Δ = 122.64; p = 0.0294; data not shown) and diminished levels of FH (Δ = 836,969; p = 0.0285; data not shown) co-existed with CVA incidence. C5a correlated storngly with blood RAGE and HMGB1, but not with viral load and immunological responsiveness. Remdesivir positively affected FH preservation, while convalescent plasma treatment elevated C5a levels. Three clusters of complement activation demonstrated a various milieu of ApoE & FH vs C5a & TCC in COVID-19 patients. Complement activation is linked to increased necrosis markers but not to viral burden or immune system response.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: HMGB1 Protein / COVID-19 Type of study: Etiology study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-17011-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: HMGB1 Protein / COVID-19 Type of study: Etiology study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-17011-7