Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies

• Published in: Journal of translational medicine Vol. 19; no. 1; p. 139
• Main Authors: Sciacchitano, Salvatore, De Vitis, Claudia, D'Ascanio, Michela, Giovagnoli, Simonetta, De Dominicis, Chiara, Laghi, Andrea, Anibaldi, Paolo, Petrucca, Andrea, Salerno, Gerardo, Santino, Iolanda, Amodeo, Rachele, Simmaco, Maurizio, Napoli, Christian, Tafuri, Agostino, Di Napoli, Arianna, Sacconi, Andrea, Salvati, Valentina, Ciliberto, Gennaro, Fanciulli, Maurizio, Piaggio, Giulia, de Latouliere, Luisa, Ricci, Alberto, Mancini, Rita
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.04.2021; BioMed Central; BMC
• Subjects: Aged; Aged, 80 and over; Blood diseases; CD3 antigen; CD38 antigen; CD4 antigen; CD8 antigen; Chronic lymphocytic leukemia; Coronavirus disease (COVID-19); Coronaviruses; COVID-19; COVID-19 - complications; Creatinine; Cytokines; Cytometry; Differentially expressed genes; Euthyroid Sick Syndromes - complications; Female; Gene expression; Genetic aspects; Health aspects; Hematologic Neoplasms - complications; Hematologic Neoplasms - genetics; Hematological malignancies; Hematology; Hodgkin's lymphoma; Humans; Immunoassay; Immunology; Intensive care units; Interleukin 6; IP-10 protein; Italy; Laboratories; Leukemia; Leukocytes (neutrophilic); Leukocytes, Mononuclear; Low T3 syndrome; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Lymphoma; Male; Malignancy; Measurement; Middle Aged; NanoString; Neutrophils; Patients; Peripheral blood mononuclear cells; Risk factors; Serum levels; Severe acute respiratory syndrome coronavirus 2; Single-Cell Analysis; Thyroid function; Thyroid gland; Triiodothyronine; Triiodothyronine - blood; Italy; United States > US; Differentially expressed genes; Thyroid function; Coronavirus disease (COVID-19); NanoString; CyTOF; Hematological malignancies; Low T3 syndrome
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-021-02805-6

Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies. Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC). Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3. Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.