biostudies-literatureThompson RCNCATS NIH HHSSwiss National Science FoundationNIDDK NIH HHSNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSNIH HHS236-246https://www.ebi.ac.uk/biostudies/studies/S-EPMC9873574biostudies-literatureUnknown29(1)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 independentlyNature medicineMolecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae.PMC9873574U24 CA224319S10 OD030463S10 OD026880UL1 TR004419CA224319310030P30 CA196521R01 AI141953NRP 781984313R01AI141953-02S1310030-200669CA1965213R01AI141953-02S2U01 DK124165DK1241654078P0-198431Agashe CSerrano SMount Sinai COVID-19 Biobank TeamVaninov NXue LPatel MMarvin RWalker LWang YCKim-Schulze SArgueta KPatel VSilva PYuan DBailey RYoung SRodrigues AStefanos HLe Berichel JCosgrove DLiharska LEFeng SVan Der Heide VHochman AZaks NJaladanki SReyes-Torres ITuballes KMerad MSebra RHeath JRBoyman OBeckmann AGMoya EMouskas KKelly GJohnson JSCossarini FGlicksberg BSMerzier ETyler SRChung JGyimesi GLeventhal MBYu AGeanon DRedes JDel Valle DMEber NMachado RDayal BThompson RCNadkarni GAkyatan AAscolillo SOnel KCedillo MAWilson KMHorta LMeyer DWacker DChien JChen STEllis EFernandes MGnjatic SDawson TDul KFishman NMaskey STin MDave AHumblin EGelb BDComella PHCimen Bozkus CJamal HJordan DSoares Schanoski AZaki NScott IMorris SSloofman LGonzalez-Kozlova EMollaoglu GAlvarez KVlachos KNisenholtz MBuckup MLee GHSweeney RHarris JCambron LArgmann CSridhar SHLacunza JBose SShervey MAlibo EYishak MRoudko VWilson JShah HHatem SMartin GWalsh HLebovitch DHartnett MBegani PWilkins LHoffman GEMahmood ZMatthews PBrown SACarrara GBarcessat VCharney AWFabris FUpadhyaya BAlesso-Carra KGangadharan SLindblad KAmabile ALee JElaiho CKim JLeech JLee GLee BPruitt CSimons NWOunadjela MDhainaut MChang CHamdani MZha RCheng EKarim SMehandru SBravo PChang SSchadt EEHerbinet MYi NRuiz EWilk CMLansky ACervia CAgrawal PStraw MHook JMar KOfori-Amanfo GWang BHandler DTeague CVaid AKang GCalorossi SHerrera ESoto JXie HLepow LWang WBurka LMeckel KRahman ARoussos PRathi SHuckins LMarron TUEaton MGrabowska JCarbonell GTabachnikova ABeckmann NDYeboah NAChowdhury MKarekar NRodriguez AFrancoeur NJMadrid KBogunovic DDornfeld RFalci DCotter LNie KBatchelor CFennessy BSmith MFaith JMercedes CScalzo PKumar ALivanos AfalseMolecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae.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 independently2023-01-01T00:00:00Z2023 Jan2026-07-14T19:09:41.473Z2025-04-04T13:37:07.465ZS-EPMC98735743648210110.1038/s41591-022-02107-4