9bd6a53f02f24494c29d9d40e251289b 296655.pdf 7cbc7e3172873b03c94a62554db6b4e9ba74d6f5 296655.pdf 1b9fb220bc4a3ffa8d6ecf35e31d0997d95ab5fbe6a2603163f3c95bbe7649a3 296655.pdf Title: Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients Subject: The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination. Keywords: COVID-19; solid organ transplant recipients; vaccination; humoral immunity; cellular; immunity Author: Bernardo Ayala-Borges, Miguel Escobedo, Natalia Egri, Sabina Herrera, Marta Crespo, Sonia Mirabet, Carlos Arias-Cabrales, Anna Vilella, Eduard Palou, María M. Mosquera, Mariona Pascal, Jordi Colmenero, Marta Farrero and Marta Bodro Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Dec 14 03:25:29 2023 CET ModDate: Thu Dec 14 03:30:53 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 860393 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GKDRGE+VnURWPalladioL Type 1 Custom yes yes no 10 0 IFZPXH+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 YLPRYZ+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 RVLWCX+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 NWYVYM+CMSY10 Type 1 Builtin yes yes no 68 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes no 72 0 ZXDKIP+EURM10 Type 1 Builtin yes yes no 76 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 83 0 KLMOKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 94 0 KLMOKM+PalatinoLinotype TrueType WinAnsi yes yes no 97 0 KLMOKO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 100 0 KLMOKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 123 0 KLMOKM+PalatinoLinotype TrueType WinAnsi yes yes no 126 0 KLMOKO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 129 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-07-27 02:45:58 CEST RepresentationInformation: 296655.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-07-26 11:59:22 CEST Size: 860393 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 288 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patient Information Destination: subsection.2.1 Item: Title: Detection of Antibodies to SARS-CoV-2 Destination: subsection.2.2 Item: Title: Detection of Cellular Response by IFN- ELISpot Destination: subsection.2.3 Item: Title: Detection of Anti-HLA Donor-Specific HLA Antibodies Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Characteristics Destination: subsection.3.1 Item: Title: Antobody and Cell Response to the mRNA-1273 Vaccine Destination: subsection.3.2 Item: Title: Factors with Association to Vaccine Unresponsiveness Destination: subsection.3.3 Item: Title: SARS-CoV-2 Infection Destination: subsection.3.4 Item: Title: Safety Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients Author: Bernardo Ayala-Borges, Miguel Escobedo, Natalia Egri, Sabina Herrera, Marta Crespo, Sonia Mirabet, Carlos Arias-Cabrales, Anna Vilella, Eduard Palou, María M. Mosquera, Mariona Pascal, Jordi Colmenero, Marta Farrero and Marta Bodro Subject: The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination. Keywords: COVID-19; solid organ transplant recipients; vaccination; humoral immunity; cellular; immunity Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Dec 14 03:25:29 CET 2023 ModDate: Thu Dec 14 03:30:53 CET 2023 ID: 0x2e73cf1a600702a01efb51f6ed20ef37, 0x2e73cf1a600702a01efb51f6ed20ef37 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: YLPRYZ+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: YLPRYZ+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: NWYVYM+CMSY10 FontSubset: true FirstChar: 2 LastChar: 21 FontDescriptor: FontName: NWYVYM+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: RVLWCX+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: RVLWCX+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GEWEQC+PazoMath-Italic FontSubset: true FirstChar: 103 LastChar: 103 FontDescriptor: FontName: GEWEQC+PazoMath-Italic Flags: Symbolic FontBBox: -70, -277, 902, 733 FontFile: true Font: BaseFont: GKDRGE+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: GKDRGE+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WLENKM+VnURWPalladioL-Bold FontSubset: true FirstChar: 189 LastChar: 189 FontDescriptor: FontName: WLENKM+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZXDKIP+EURM10 FontSubset: true FirstChar: 11 LastChar: 22 FontDescriptor: FontName: ZXDKIP+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: IFZPXH+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: IFZPXH+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 82, 279, 152, 288 Annotation: Subtype: Link Rect: 34, 268, 117, 276 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 150, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 236, 642, 247, 655 Annotation: Subtype: Link Rect: 399, 642, 410, 655 Annotation: Subtype: Link Rect: 106, 629, 117, 643 Annotation: Subtype: Link Rect: 226, 629, 237, 643 Annotation: Subtype: Link Rect: 305, 629, 316, 643 Annotation: Subtype: Link Rect: 121, 617, 132, 630 Annotation: Subtype: Link Rect: 450, 617, 461, 630 Annotation: Subtype: Link Rect: 116, 17, 270, 28 Annotation: Subtype: Link Rect: 406, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 388, 87, 407 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 364, 707, 371, 716 ActionDest: 144 Annotation: Subtype: Link Rect: 372, 707, 379, 716 ActionDest: 144 Annotation: Subtype: Link Rect: 430, 670, 437, 679 ActionDest: 144 Annotation: Subtype: Link Rect: 248, 645, 255, 654 ActionDest: 144 Annotation: Subtype: Link Rect: 255, 644, 262, 654 ActionDest: 144 Annotation: Subtype: Link Rect: 414, 619, 421, 629 ActionDest: 144 Annotation: Subtype: Link Rect: 549, 582, 556, 591 ActionDest: 144 Annotation: Subtype: Link Rect: 396, 557, 403, 566 ActionDest: 144 Annotation: Subtype: Link Rect: 403, 557, 410, 566 ActionDest: 144 Annotation: Subtype: Link Rect: 522, 506, 534, 516 ActionDest: 144 Annotation: Subtype: Link Rect: 534, 507, 546, 516 ActionDest: 144 Annotation: Subtype: Link Rect: 237, 481, 249, 490 ActionDest: 144 Annotation: Subtype: Link Rect: 247, 431, 259, 440 ActionDest: 147 Annotation: Subtype: Link Rect: 260, 431, 272, 440 ActionDest: 147 Annotation: Subtype: Link Rect: 254, 218, 261, 227 ActionDest: 144 Page: Sequence: 3 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 276, 568, 283, 580 ActionDest: 80 Annotation: Subtype: Link Rect: 363, 556, 370, 568 ActionDest: 80 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 218, 315, 225, 327 ActionDest: 107 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 316, 251, 323, 263 ActionDest: 135 Annotation: Subtype: Link Rect: 212, 175, 219, 188 ActionDest: 135 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 328, 150, 335, 162 ActionDest: 138 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 385, 375, 392, 387 ActionDest: 135 Annotation: Subtype: Link Rect: 310, 362, 317, 374 ActionDest: 135 Annotation: Subtype: Link Rect: 327, 252, 339, 261 ActionDest: 147 Annotation: Subtype: Link Rect: 344, 126, 356, 135 ActionDest: 144 Annotation: Subtype: Link Rect: 357, 126, 369, 135 ActionDest: 147 Annotation: Subtype: Link Rect: 282, 88, 294, 97 ActionDest: 144 Annotation: Subtype: Link Rect: 257, 63, 269, 72 ActionDest: 147 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 302, 723, 314, 732 ActionDest: 147 Annotation: Subtype: Link Rect: 259, 698, 271, 707 ActionDest: 147 Annotation: Subtype: Link Rect: 453, 635, 460, 644 ActionDest: 144 Annotation: Subtype: Link Rect: 460, 635, 472, 644 ActionDest: 147 Annotation: Subtype: Link Rect: 473, 635, 485, 644 ActionDest: 147 Annotation: Subtype: Link Rect: 304, 622, 316, 631 ActionDest: 147 Annotation: Subtype: Link Rect: 319, 623, 331, 631 ActionDest: 147 Annotation: Subtype: Link Rect: 479, 547, 491, 556 ActionDest: 147 Annotation: Subtype: Link Rect: 491, 547, 503, 556 ActionDest: 147 Annotation: Subtype: Link Rect: 295, 522, 302, 531 ActionDest: 144 Annotation: Subtype: Link Rect: 302, 522, 314, 531 ActionDest: 147 Annotation: Subtype: Link Rect: 315, 522, 327, 531 ActionDest: 147 Annotation: Subtype: Link Rect: 361, 434, 373, 443 ActionDest: 147 Annotation: Subtype: Link Rect: 373, 434, 385, 443 ActionDest: 147 Annotation: Subtype: Link Rect: 393, 422, 405, 431 ActionDest: 144 Annotation: Subtype: Link Rect: 406, 422, 418, 431 ActionDest: 147 Annotation: Subtype: Link Rect: 418, 422, 430, 431 ActionDest: 147 Annotation: Subtype: Link Rect: 431, 422, 443, 431 ActionDest: 147 Annotation: Subtype: Link Rect: 443, 422, 455, 431 ActionDest: 147 Annotation: Subtype: Link Rect: 456, 422, 468, 431 ActionDest: 147 Annotation: Subtype: Link Rect: 416, 309, 428, 318 ActionDest: 147 Annotation: Subtype: Link Rect: 456, 283, 468, 293 ActionDest: 151 Annotation: Subtype: Link Rect: 469, 283, 481, 293 ActionDest: 151 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 144, 404, 182, 414 Annotation: Subtype: Link Rect: 188, 404, 224, 414 Annotation: Subtype: Link Rect: 478, 380, 515, 391 Annotation: Subtype: Link Rect: 521, 380, 557, 391 Annotation: Subtype: Link Rect: 259, 311, 296, 322 Annotation: Subtype: Link Rect: 303, 311, 339, 322 Annotation: Subtype: Link Rect: 157, 288, 365, 299 Annotation: Subtype: Link Rect: 175, 253, 212, 264 Annotation: Subtype: Link Rect: 218, 253, 254, 264 Annotation: Subtype: Link Rect: 285, 219, 322, 230 Annotation: Subtype: Link Rect: 328, 219, 364, 230 Annotation: Subtype: Link Rect: 340, 196, 377, 207 Annotation: Subtype: Link Rect: 59, 162, 96, 172 Annotation: Subtype: Link Rect: 206, 127, 243, 138 Annotation: Subtype: Link Rect: 140, 93, 177, 103 Annotation: Subtype: Link Rect: 286, 69, 324, 80 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 59, 699, 96, 710 Annotation: Subtype: Link Rect: 519, 676, 557, 687 Annotation: Subtype: Link Rect: 59, 665, 95, 675 Annotation: Subtype: Link Rect: 519, 629, 557, 640 Annotation: Subtype: Link Rect: 59, 619, 95, 629 Annotation: Subtype: Link Rect: 515, 595, 553, 606 Annotation: Subtype: Link Rect: 59, 550, 96, 560 Annotation: Subtype: Link Rect: 397, 514, 434, 525 Annotation: Subtype: Link Rect: 441, 514, 477, 525 Annotation: Subtype: Link Rect: 485, 457, 522, 468 Annotation: Subtype: Link Rect: 163, 434, 200, 445 Annotation: Subtype: Link Rect: 364, 399, 402, 410 Annotation: Subtype: Link Rect: 408, 365, 446, 376 Annotation: Subtype: Link Rect: 452, 365, 488, 376 Annotation: Subtype: Link Rect: 390, 330, 427, 341 Annotation: Subtype: Link Rect: 434, 330, 470, 341 Annotation: Subtype: Link Rect: 198, 296, 235, 307 Annotation: Subtype: Link Rect: 242, 296, 278, 307 Annotation: Subtype: Link Rect: 306, 261, 343, 272 Annotation: Subtype: Link Rect: 519, 238, 557, 249 Annotation: Subtype: Link Rect: 59, 228, 95, 238 Annotation: Subtype: Link Rect: 223, 193, 261, 203 Annotation: Subtype: Link Rect: 286, 158, 323, 169 Annotation: Subtype: Link Rect: 346, 135, 383, 146 Annotation: Subtype: Link Rect: 342, 100, 379, 111 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 519, 722, 557, 733 Annotation: Subtype: Link Rect: 59, 711, 95, 721 Annotation: Subtype: Link Rect: 127, 676, 164, 687 Annotation: Subtype: Link Rect: 170, 676, 206, 687 Checksum: d4a3663f Type: CRC32 Checksum: 9bd6a53f02f24494c29d9d40e251289b Type: MD5 Checksum: 7cbc7e3172873b03c94a62554db6b4e9ba74d6f5 Type: SHA-1 Checksum: 1b9fb220bc4a3ffa8d6ecf35e31d0997d95ab5fbe6a2603163f3c95bbe7649a3 Type: SHA-256