f13be9503e75e7c89cb00db8739276c5 pmc_10047501.pdf fe6b33829cca50b9f62b60c9624c547bef39d59b pmc_10047501.pdf d39f5e192ada9abd12079d796b74df371409600f4ef7f0331eef60afc2e7720e pmc_10047501.pdf Title: Biomarker Profiles Associated with COVID-19 Severity and Mortality Subject: Introduction: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. Methods: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-ɣ, MCP-1, MIP-1, and TNF-) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. Results: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). Conclusions: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients. Keywords: COVID-19; cytokines; serum; lung fibrosis Author: Silvia Sánchez-Díez, Carlos Gómez-Ollés, María-Jesús Cruz, Miquel de Homdedeu, David Espejo, Jaume Ferrer, Oriol Roca, Andrés Pacheco and Xavier Muñoz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Mar 1 09:25:43 2023 CET ModDate: Wed Mar 1 09:29:08 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2845988 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QDCWHF+EURM10 Type 1 Builtin yes yes no 10 0 IBAVXE+TeX-tipa9 Type 1 Builtin yes yes no 14 0 LTOCFS+URWPalladioL-Bold Type 1 Custom yes yes no 18 0 RORASQ+URWPalladioL-Roma Type 1 Custom yes yes no 23 0 ODNKPB+URWPalladioL-Ital Type 1 Custom yes yes no 27 0 DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 31 0 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BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 280 0 BCDIEE+MS-Gothic CID TrueType Identity-H yes yes yes 286 0 AXGJOC+VnURWPalladioL Type 1 Custom yes yes no 308 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-01-24 02:36:08 CET RepresentationInformation: pmc_10047501.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-07-28 02:24:08 CEST Size: 2845988 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 476 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Material and Methods Destination: section.2 Children: Item: Title: Study Population Destination: subsection.2.1 Item: Title: Pulmonary Function Testing Destination: subsection.2.2 Item: Title: Chest HRCT Scanning Destination: subsection.2.3 Item: Title: Cytokine Analysis Destination: subsection.2.4 Item: Title: YKL-40 and KL-6 Analysis Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Study Population Destination: subsection.3.1 Item: Title: Cytokine Expression Profiles Destination: subsection.3.2 Item: Title: Levels of Pulmonary Fibrosis Biomarkers Destination: subsection.3.3 Item: Title: Relation between Mortality and Cytokines or Pulmonary Fibrotic Biomarkers Destination: subsection.3.4 Item: Title: Predictive Value of Cytokines and Pulmonary Fibrotic Biomarkers Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Biomarker Profiles Associated with COVID-19 Severity and Mortality Author: Silvia Sánchez-Díez, Carlos Gómez-Ollés, María-Jesús Cruz, Miquel de Homdedeu, David Espejo, Jaume Ferrer, Oriol Roca, Andrés Pacheco and Xavier Muñoz Subject: ぉのぴひはつふっぴどはの〺〠ごとづ〠ちどね〠はて〠ぴとどび〠びぴふつべ〠ぷちび〠ぴは〠ちのちぬべぺづ〠ぢどはねちひにづひび〠ぴとちぴ〠ねどでとぴ〠ばひづつどっぴ〠ぴとづ〠びづぶづひどぴべ〠ちのつ〠ばひはでひづびびどはの〠はて〠ぴとづ〠こぁげこ〭ぃはざ〭〲〠どのてづっぴどはの〬〠ぢはぴと〠どの〠ぴとづ〠ちっふぴづ〠ばとちびづ〠ちのつ〠ちてぴづひ〠ひづっはぶづひべ〮〠きづぴとはつび〺〠さのぶちっっどのちぴづつ〠ばちぴどづのぴび〠どのてづっぴづつ〠ぷどぴと〠ぴとづ〠はひどでどのちぬ〠びぴひちどの〠はて〠ぃくざぉい〭〱〹〠ひづぱふどひどので〠ぷちひつ〠〨ぇひはふば〠〱〬〠の〠〽〠〴〸〩〠はひ〠ぉぃさ〠〨ぇひはふば〠〲〬〠の〠〽〠〴〱〩〠ちつねどびびどはの〠ぷづひづ〠どのっぬふつづつ〮〠ぁぴ〠ぴとづ〠ぴどねづ〠はて〠ちつねどびびどはの〠〨ぶどびどぴ〠〱〩〬〠ち〠っぬどのどっちぬ〠とどびぴはひべ〠ぷちび〠ちっぱふどひづつ〬〠ちのつ〠ぢぬははつ〠びちねばぬづび〠ぷづひづ〠はぢぴちどのづつ〮〠くのづ〠ちのつ〠びどへ〠ねはのぴとび〠ちてぴづひ〠つどびっとちひでづ〠てひはね〠ぴとづ〠とはびばどぴちぬ〠〨ぶどびどぴび〠〲〠ちのつ〠〳〬〠ひづびばづっぴどぶづぬべ〩〬〠ち〠っぬどのどっちぬ〠とどびぴはひべ〬〠ぬふので〠てふのっぴどはの〠ぴづびぴび〬〠ちのつ〠ぢぬははつ〠びちねばぬづび〠ぷづひづ〠っちひひどづつ〠はふぴ〮〠ぁぴ〠ぶどびどぴ〠〲〬〠ばちぴどづのぴび〠ちぬびは〠ふのつづひぷづのぴ〠ち〠っとづびぴ〠ぃご〠びっちの〮〠いどててづひづのぴ〠っべぴはにどのづび〠〨ぉが〭〱〬〠ぉが〭〲〬〠ぉが〭〴〬〠ぉが〭〵〬〠ぉが〭〶〬〠ぉが〭〷〬〠ぉが〭〸〬〠ぉが〭〱〰〬〠ぉが〭〱〲ば〷〰〬〠ぉが〭〱〳〬〠ぉが〭〱〷ぁ〬〠ぇ〭ぃこう〬〠ぇき〭ぃこう〬〠ぉうぎ〭㉣〬〠きぃぐ〭〱〬〠きぉぐ〭〱〬〠ちのつ〠ごぎう〭〩〠ちのつ〠ぬふので〠てどぢひはびどび〠ぢどはねちひにづひび〠〨すかが〭〴〰〠ちのつ〠かが〭〶〩〠ぷづひづ〠ねづちびふひづつ〠どの〠ぢぬははつ〠びちねばぬづび〠はぢぴちどのづつ〠ちぴ〠ぶどびどぴび〠〱〬〠〲〬〠ちのつ〠〳〮〠げづびふぬぴび〺〠ぁぴ〠ぶどびどぴ〠〱〬〠ぉが〭〴〬〠ぉが〭〵〬〠ちのつ〠ぉが〭〶〠ぬづぶづぬび〠ぷづひづ〠とどでとづひ〠どの〠ぇひはふば〠〲〠〨ば〠〽〠〰〮〰〳〹〬〠〰〮〰〱〱〬〠ちのつ〠〰〮〰〴〵〬〠ひづびばづっぴどぶづぬべ〩〬〠ちのつ〠ぉが〭〱〷〠ちのつ〠ぉが〭〸〠ぬづぶづぬび〠ぷづひづ〠とどでとづひ〠どの〠ぇひはふば〠〱〠〨ば〠〽〠〰〮〰〲〶〠ちのつ〠〰〮〰〰〱〬〠ひづびばづっぴどぶづぬべ〩〮〠ごとづ〠のふねぢづひ〠はて〠ばちぴどづのぴび〠どの〠ぇひはふばび〠〱〠ちのつ〠〲〠ぷとは〠つどづつ〠つふひどので〠とはびばどぴちぬどぺちぴどはの〠ぷちび〠〸〠ちのつ〠〱〱〬〠ひづびばづっぴどぶづぬべ〮〠すかが〭〴〰〠ちのつ〠かが〭〶〠ぬづぶづぬび〠ぷづひづ〠とどでとづひ〠どの〠ばちぴどづのぴび〠ぷとは〠つどづつ〮〠こづひふね〠すかが〭〴〰〠ちのつ〠かが〭〶〠ぬづぶづぬび〠つづぴづひねどのづつ〠ちぴ〠ぶどびどぴ〠〲〠っはひひづぬちぴづつ〠のづでちぴどぶづぬべ〠ぷどぴと〠うざぃ〠〨ば〠〽〠〰〮〰〲〲〠ちのつ〠ば〠〽〠〰〮〰〲〴〬〠ひづびばづっぴどぶづぬべ〩〠ちのつ〠うぅざ〱〠〨ば〠〽〠〰〮〰〱〲〠ちのつ〠ば〠〽〠〰〮〰〳〲〬〠ひづびばづっぴどぶづぬべ〩〠ねづちびふひづつ〠ちぴ〠ぶどびどぴ〠〳〮〠かが〭〶〠ぬづぶづぬび〠ちぬびは〠っはひひづぬちぴづつ〠のづでちぴどぶづぬべ〠ぷどぴと〠ぴとづ〠つどててふびどので〠っちばちっどぴべ〠はて〠ぴとづ〠ぬふのでび〠てはひ〠っちひぢはの〠ねはのはへどつづ〠〨いがぃく〬〠ば〠〽〠〰〮〰〰〱〩〮〠ぃはのっぬふびどはのび〺〠ぐちぴどづのぴび〠ぷとは〠ひづぱふどひづつ〠ぉぃさ〠ちつねどびびどはの〠とちつ〠とどでとづひ〠ぬづぶづぬび〠はて〠ごと〲〠っべぴはにどのづび〬〠ぷとどぬづ〠ばちぴどづのぴび〠ちつねどぴぴづつ〠ぴは〠ぴとづ〠ぷちひつ〠びとはぷづつ〠ちの〠どののちぴづ〠どねねふのづ〠ひづびばはのびづ〠ちっぴどぶちぴどはの〬〠ぷどぴと〠ぉが〭〸〠ひづぬづちびづ〠ちのつ〠ごと〱〯ごと〱〷〠ぬべねばとはっべぴづ〠っはのぴひどぢふぴどはの〮〠ぉのっひづちびづつ〠ぬづぶづぬび〠はて〠すかが〭〴〰〠ちのつ〠かが〭〶〠ぷづひづ〠ちびびはっどちぴづつ〠ぷどぴと〠ねはひぴちぬどぴべ〠どの〠ぃくざぉい〭〱〹〠ばちぴどづのぴび〮 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