Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis

Abstract

Background In some patients, symptoms may persist after COVID-19, defined as Long COVID. Its pathogenesis is still debated and many hypotheses have raised. Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing Post COVID-19 syndrome to detect any deficiencies that may explain Long COVID. Design A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a post-infection period of 3 months or less to 15 months, divided into two groups. The first group (G1) comprised of fully recovered patients, while the second group (G2) included patients experiencing Long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions. Results 64 patients were divided into two groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1(p = 0.045). For the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (p = 0.045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (p = 0.01). For the somatotroph axis, the IGF-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (p = 0.369). The peak GH level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (p = 0.041). Conclusions The results showed that Long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain the Long COVID.

Trends in Traumatic Brain Injuries During the COVID-19 Pandemic: A Single-Center Review of Patient Charts From Pakistan

“…Replicating such studies with a significantly larger sample size and involving multi-center reporting can add weight to the conclusions drawn above. In the post-COVID era, newer studies examine the implications, impact, and possible explanations (including Long-COVID) for shifts in TBI epidemiology worldwide [29,30].…”

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

“…( 27 ) observed reduced immunostaining of corticotropic, somatotropic, and thyrotropic cells in SARS-CoV-infected patients. In addition, given the high genetic similarity between SARS-CoV and SARS-CoV-2, adenohypophysitis has also been observed during the acute phase of COVID-19, with secondary adrenal insufficiency being higher in patients with long COVID (LC) ( 20 , 28 – 35 ).…”

“…Among the mechanisms associated with the development of LC and ME/CFS are viral persistence, immunological alteration, the appearance of autoimmune diseases and hormonal imbalances ( 129 , 273 – 275 ). Both exhibit CD8 T-cell hyperactivation, T-cell exhaustion, and hypopituitarism ( 28 , 30 , 52 , 53 , 273 , 276 – 279 ). In addition, decreased levels of DHEA-S in ME/CFS and testosterone in LC have been observed ( 280 – 287 ).…”