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1. SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Author

Banco Santander, Consejo Superior de Investigaciones Científicas (España), Conferencia de Rectores de las Universidades Españolas, Xunta de Galicia, Álvarez, Hortensia [0000-0002-5002-1737], Ruiz-Mateos, Ezequiel [0000-0001-6747-7813], Vitallé, Joana [0000-0002-5292-1851], Vieitez, Irene [0000-0001-9241-0207], Pérez-Gómez, Alberto [0000-0002-3644-2914], Gallego-García, Pilar [0000-0001-8531-9851], Chiara , Loretta de [0000-0001-7700-6417], Poveda, Eva [0000-0003-4835-9875], Posada, David [0000-0003-1407-3406], Llibre, Josep María [0000-0002-7158-6753], Álvarez, Hortensia, Ruiz-Mateos, Ezequiel, Juiz-González, Pedro Miguel, Vitallé, Joana, Vieitez, Irene, Vázquez-Friol, María del Carmen, Torres-Beceiro, Isabel, Pérez-Gómez, Alberto, Gallego-García, Pilar, Estévez-Gómez, Nuria, Chiara , Loretta de, Poveda, Eva, Posada, David, Llibre, Josep María, Banco Santander, Consejo Superior de Investigaciones Científicas (España), Conferencia de Rectores de las Universidades Españolas, Xunta de Galicia, Álvarez, Hortensia [0000-0002-5002-1737], Ruiz-Mateos, Ezequiel [0000-0001-6747-7813], Vitallé, Joana [0000-0002-5292-1851], Vieitez, Irene [0000-0001-9241-0207], Pérez-Gómez, Alberto [0000-0002-3644-2914], Gallego-García, Pilar [0000-0001-8531-9851], Chiara , Loretta de [0000-0001-7700-6417], Poveda, Eva [0000-0003-4835-9875], Posada, David [0000-0003-1407-3406], Llibre, Josep María [0000-0002-7158-6753], Álvarez, Hortensia, Ruiz-Mateos, Ezequiel, Juiz-González, Pedro Miguel, Vitallé, Joana, Vieitez, Irene, Vázquez-Friol, María del Carmen, Torres-Beceiro, Isabel, Pérez-Gómez, Alberto, Gallego-García, Pilar, Estévez-Gómez, Nuria, Chiara , Loretta de, Poveda, Eva, Posada, David, and Llibre, Josep María

Abstract

Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.

Published
2022

2. SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Author

Hortensia Álvarez, Ezequiel Ruiz-Mateos, Pedro Miguel Juiz-González, Joana Vitallé, Irene Viéitez, María del Carmen Vázquez-Friol, Isabel Torres-Beceiro, Alberto Pérez-Gómez, Pilar Gallego-García, Nuria Estévez-Gómez, Loretta De Chiara, Eva Poveda, David Posada, Josep M. Llibre, Banco Santander, Consejo Superior de Investigaciones Científicas (España), Conferencia de Rectores de las Universidades Españolas, Xunta de Galicia, Álvarez, Hortensia [0000-0002-5002-1737], Ruiz-Mateos, Ezequiel [0000-0001-6747-7813], Vitallé, Joana [0000-0002-5292-1851], Vieitez, Irene [0000-0001-9241-0207], Pérez-Gómez, Alberto [0000-0002-3644-2914], Gallego-García, Pilar [0000-0001-8531-9851], Chiara , Loretta de [0000-0001-7700-6417], Poveda, Eva [0000-0003-4835-9875], Posada, David [0000-0003-1407-3406], Llibre, Josep María [0000-0002-7158-6753], Álvarez, Hortensia, Ruiz-Mateos, Ezequiel, Vitallé, Joana, Vieitez, Irene, Pérez-Gómez, Alberto, Gallego-García, Pilar, Chiara , Loretta de, Poveda, Eva, Posada, David, and Llibre, Josep María

Subjects
Microbiology (medical), CD4+ T cell response, 2412 Inmunología, 3202 Epidemiología, QH301-705.5, SARS-CoV-2, viruses, fungi, virus diseases, HIV, Case Report, Microbiology, body regions, Virology, 2420.08 Virus Respiratorios, Biology (General), skin and connective tissue diseases
Abstract

Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence., This work was partially funded by grant EPICOVIGAL from FONDO SUPERA-COVID19 from Banco Santander-CSIC-CRUE and grant CT850A-2 from ACIS SERGAS from the Consellería de Sanidade of Xunta de Galicia, Spain, to D.P.

Published
2022

3. Elevated Anti-SARS-CoV-2 Antibodies and IL-6, IL-8, MIP-1β, Early Predictors of Severe COVID-19

Author

Vasso Skouridou, Ana Serna-Gallego, Manuel Crespo, Ezequiel Ruiz-Mateos, Alexandre Pérez, Alicia Gutierrez-Valencia, Esperanza Muñoz-Muela, Ciara K. O'Sullivan, Maria Trujillo-Rodriguez, María M Bobillo, Cristina Martínez, Jorge Julio Cabrera-Alvar, Lucia Patiño, Irene Vieitez, Eva Poveda, Mariluz Botero-Gallego, Helena Codina, [Codina,H, Patiño,L, Bobillo,MM, Pérez,A, Poveda,E] Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVigo, Vigo, Spain. [Vieitez,I] Rare Diseases & Pediatric Medicine Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-Uvigo, Vigo, Spain. [Gutierrez-Valencia,A, Serna-Gallego,A, Trujillo-Rodríguez,M, Muñoz-Muela,E, Ruiz-Mateos,E] Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain. [Skouridou,V, Botero-Gallego,M, O’Sullivan,CK] INTERFIBIO Consolidated Research Group, Departament d’ Enginyeria Quimica, Universitat Rovira i Virgili, Tarragona, Spain. [Martínez,C] Methodology and Statistics Unit, Galicia Sur Health Research Institute (IIS Galicia Sur)-Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, Vigo, Spain. [Pérez,A, Crespo,M] Infectious Diseases Unit, Department of Internal Medicine, Complexo Hospitalario Universitario de Vigo, IIS Galicia Sur, SERGAS-UVigo, Vigo, Spain. [Cabrera-Alvar,JJ] Microbiology Service, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-Uvigo, Vigo, Spain. [O'Sullivan,CK] Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain., This work was supported by the Plan Estatal de I+D+I 2013-2016 and 2017–2020 and cofinanced by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la investigación del Fondo Europeo de Desarrollo Regional (FEDER), Fondo COVID19 of Instituto de Salud Carlos III (COV20/00698), RETICS, Red de Investigación en SIDA [RD16/0025/0026], and Fundación Biomédica Galicia Sur. E.R-M. was supported by the Spanish Research Council (CSIC) and by the research grant CV20-85418 from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades (Junta de Andalucía). A.P. was supported by the Instituto de Salud Carlos III, Subprograma Rio Hortega (CM20/00243). A.G.-V. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund ('A way to achieve Europe'), Subprograma Miguel Servet (CP19/00159). E.M.M. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund ('A way to achieve Europe'), Subprogram PFIS (FI19/00304). C.K. was supported by Fondo COVID19 of Instituto de Salud Carlos III (COV20/00823)., Instituto de Salud Carlos III, European Commission, Fundación Biomédica Galicia Sur, Consejo Superior de Investigaciones Científicas (España), Junta de Andalucía, Vieitez, Irene [0000-0001-9241-0207], Poveda, Eva [0000-0003-4835-9875], Vieitez, Irene, Poveda, Eva, Red Española de Investigación en SIDA, Martínez, Cristina, Trujillo-Rodríguez, María, Muñoz-Muela, Esperanza, Pérez-González, Alexandre, Cabrera-Alvar, Jorge Julio, Martínez, Cristina [0000-0002-9073-3464], Trujillo-Rodríguez, María [0000-0002-4716-4294], Muñoz-Muela, Esperanza [0000-0002-5432-986X], Pérez-González, Alexandre [0000-0003-4836-6768], and Cabrera-Alvar, Jorge Julio [0000-0002-0397-0868]

Subjects
Phenomena and Processes::Physical Phenomena::Mechanical Phenomena::Kinetics [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [Medical Subject Headings], severe COVID-19, Disease, Gastroenterology, law.invention, Persistence (computer science), Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], law, Diagnosis, Viral load, Biology (General), Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-8 [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin M [Medical Subject Headings], biology, Diagnóstico, Anti-SARS-CoV-2 antibodies, Citocinas, Intensive care unit, viral load, Cytokines, Antibody, anti-SARS-CoV-2 antibodies, Microbiology (medical), medicine.medical_specialty, Anticuerpos, QH301-705.5, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1 [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Microbiology, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care Units [Medical Subject Headings], Article, Proinflammatory cytokine, Immune system, Virology, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Viral [Medical Subject Headings], Interleukin 8, Interleukin 6, Beta (finance), Severe COVID-19, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin A [Medical Subject Headings], business.industry, SARS-CoV-2, COVID-19, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], cytokines, Carga viral, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], biology.protein, RNA, business, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G [Medical Subject Headings]
Abstract

Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels’ decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity., This work was supported by the Plan Estatal de I+D+I 2013-2016 and 2017–2020 and cofinanced by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la investigación del Fondo Europeo de Desarrollo Regional (FEDER), Fondo COVID19 of Instituto de Salud Carlos III (COV20/00698), RETICS, Red de Investigación en SIDA [RD16/0025/0026]; and Fundación Biomédica Galicia Sur. E.R-M. was supported by the Spanish Research Council (CSIC) and by the research grant CV20-85418 from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades (Junta de Andalucía). A.P. was supported by the Instituto de Salud Carlos III, Subprograma Rio Hortega (CM20/00243). A.G.-V. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (CP19/00159). E.M.M. was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprogram PFIS (FI19/00304). C.K. was supported by Fondo COVID19 of Instituto de Salud Carlos III (COV20/00823).

Published
2021

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