Journal
NATURE MEDICINE
Volume -, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-022-02107-4
Keywords
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Funding
- Mount Sinai COVID-19 Informatics Center
- Department of Genetics and Genomic Sciences
- Human Immune Monitoring Center
- Program for the Protection of Human Subjects
- Department of Psychiatry
- Department of Medicine
- Department of Oncological Sciences
- Department of Pediatrics
- Precision Immunology Institute
- Tisch Cancer Institute
- Icahn Institute for Data Science and Genomic Technology
- Friedman Brain Institute
- Charles Bronfman Institute of Personalized Medicine
- Hasso Plattner Institute for Digital Health
- Mindich Child Health and Development Institute
- Black Family Stem Cell Institute
- National Cancer Institute U24 grant [CA224319, U01 DK124165, U24 CA196521]
- Swiss National Science Foundation grants [4078P0-198431, 310030-200669]
- National Institute of Allergy and Infectious Diseases [3R01AI141953-02S1, 3R01AI141953-02S2]
- Swiss National Science Foundation (SNF) [4078P0_198431] Funding Source: Swiss National Science Foundation (SNF)
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The post-acute sequelae of SARS-CoV-2 infection are already detectable during the acute phase and are associated with specific gene expression patterns and immune response, including antibody levels.
Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
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