DETECTION of CIRCULATING and AIRWAY AUTOANTIBODIES to IFN in SEVERE COVID-19 PATIENTS
Topics in Antiviral Medicine
; 30(1 SUPPL):117, 2022.
Article
in English
| EMBASE | ID: covidwho-1880227
ABSTRACT
Background:
Evidence suggest that critically ill COVID-19 patients have an impairment of IFN-I response. This defect in antiviral mechanisms is explained in some patients by the presence of anti IFN-alpha neutralizing autoantibodies (NAbs). However, whether NAbs fluctuate longitudinally during COVID-19, and what are their specificity toward IFN-I subtypes and consequences on the IFN response remain elusive.Methods:
Binding antibodies (BAbs) to IFN-alpha and IFN-beta were screened in serum samples (n=360) of COVID-19 patients using ELISA assays. All serum samples containing BAbs were processed to investigate NAbs using antiviral bioassay. Respiratory samples (n=17) were also included for the NAbs analysis. Transcript levels of IFN-alpha, IFN-beta, IFN-omega and IFN stimulated genes (ISGs) were analyzed through RT/Real Time PCR.Results:
Results showed that 16.94% (61/360) of COVID-19 patients had circulating BAbs against IFN-alpha and IFN-beta. Further, 21% (13/61) of critically ill subjects had NAbs with a variable titer against all the IFN-alpha subtypes (70-71680 TRU/ml) while only 1 patient had anti IFN-beta NAbs. About 70% of these serum samples showed cross reactivity to IFN-omega at different extent (27-106667 TRU/ml). Longitudinal evaluation at different time points after hospitalization indicate the persistence of high NAbs titer throughout the time. NAbs to IFN-alpha (10-20 TRU/ml) were also detected in 17.64% of respiratory samples. Patients with NAbs had severe disease and exhibited alterations in the levels of many hematological indicators [(white blood cells, neutrophils, platelets, neutrophils to lymphocytes ratio, platelets to lymphocytes ratio, D-dimer, C-reactive protein and lactate dehydrogenase;p<0.05)]. Transcriptomic analysis indicated that levels of IFN genes were lower in NAbs patients than in healthy donors (p≤0.05). However, only the ISGs levels were reduced compared to those found in the NAbs negative patients. Of note, expression of ISGs, was abolished during hospitalization in all patients with persistent high titer of NAbs.Conclusion:
Our finding demonstrate that NAbs with a broad specificity to IFN-I can be found in blood and respiratory samples from severe COVID-19 patients. NAbs detection was associated with a defective IFN response and with an increased levels of markers of disease severity.
alpha interferon; antivirus agent; autoantibody; beta interferon; C reactive protein; D dimer; endogenous compound; lactate dehydrogenase; adult; airway; bioassay; conference abstract; controlled study; coronavirus disease 2019; critically ill patient; cross reaction; enzyme linked immunosorbent assay; female; gene expression; genetic transcription; hospitalization; human; human cell; human tissue; leukocyte; longitudinal study; lymphocyte; major clinical study; male; neutrophil; protein expression; real time polymerase chain reaction; thrombocyte
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2022
Document Type:
Article
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