Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 8; pp. 2243 - 2253
• Main Authors: Poma, Anello Marcello, Proietti, Agnese, Macerola, Elisabetta, Bonuccelli, Diana, Conti, Marco, Salvetti, Alessandra, Dolo, Vincenza, Chillà, Andrea, Basolo, Alessio, Santini, Ferruccio, Toniolo, Antonio, Basolo, Fulvio
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.08.2022
• Subjects: Adrenocorticotropic hormone; Anopheles; Antigens; Biological response modifiers; Cell activation; Clinical; Coronaviruses; COVID-19; Cytotoxicity; Disease transmission; Electrons; Epstein-Barr virus; Gene expression; Genes; Genomes; Genomics; Health aspects; Heart; Hospital patients; Hybridization; Immunohistochemistry; Interferon; Leukocytes (neutrophilic); Medical equipment and supplies industry; Medical test kit industry; Pituitary; Pituitary (posterior); Pituitary gland; Pituitary hormones; Polymerase chain reaction; Reverse transcription; RNA; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Transcription activation; Transmission electron microscopy; Tropism; Viral infections; Viruses; United States; COVID-19; SARS-CoV-2; hypophysis; pituitary gland; gene expression; pituitary hormones
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgac312

Abstract Context Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum adrenocorticotropic hormone (ACTH) levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated. Objective To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes. Methods SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time reverse transcription polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry, and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay. Results The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2–positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization, and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus positivity. Conclusion Our study supports the tropism of SARS-CoV-2 for human pituitary and encourages exploration of pituitary dysfunction after COVID-19.