Tag: long covid hypothesis

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

Abstract:

Context: In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised.

Objective: 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.

Methods: A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised 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: A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P = .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 = .045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P = .01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P = .369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P = .041).

Conclusion: 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 long COVID.

Source: Taieb Ach, Nassim Ben Haj Slama, Asma Gorchane, Asma Ben Abdelkrim, Meriem Garma, Nadia Ben Lasfar, Foued Bellazreg, Widéd Debbabi, Wissem Hachfi, Molka Chadli Chaieb, Monia Zaouali, Amel Letaief, Koussay Ach, Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis, Journal of the Endocrine Society, Volume 8, Issue 3, March 2024, bvae003, https://doi.org/10.1210/jendso/bvae003 https://academic.oup.com/jes/advancearticle/doi/10.1210/jendso/bvae003/7517018 (Full text)

Role of Tau protein in long COVID and potential therapeutic targets

Abstract:

Introduction: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

Pathophysiology: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies.

Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies.

Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

Source: Marwaha B. Role of Tau protein in long COVID and potential therapeutic targets. Front Cell Infect Microbiol. 2023 Oct 25;13:1280600. doi: 10.3389/fcimb.2023.1280600. PMID: 37953801; PMCID: PMC10634420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634420/ (Full text)

Long-term neurological implications of severe acute respiratory syndrome coronavirus 2 infections in neonates: Innate immune memory and chronic neuroinflammation

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause long-term neurological complications in adults. However, the mechanisms by which early-life SARS-CoV-2 infection increases the risk of abnormal neurodevelopment remain unknown.

Recent studies have shown an association with chronic proinflammatory cytokine/chemokine production in the central nervous system (CNS). Therefore, it was hypothesised that innate immune activation and induction of innate immune memory may play a potential role in the neonatal brain. Haematopoietic stem cells in the bone marrow are exposed to SARS-CoV-2, SARS-CoV-2 envelope protein (E protein), lipopolysaccharide (LPS)-bound spike proteins (S1 and S2 proteins), and damage-associated molecular patterns (DAMPs). Myeloid progenitors enter the stroma of the choroid plexus and are further directed to incessantly supply the brain parenchyma with resident innate immune cells. The S proteins-LPS complex can cross the blood–brain barrier and plays an important role in microglial and astrocytic inflammatory responses and innate immune memory.

Persistently activated microglia with memory release pro-inflammatory cytokines/chemokines which contribute to abnormal synaptic development in the frontal lobe and cerebellum, potentially leading to long-term neurological complications, similar to those observed in autism spectrum disorder (ASD). In addition, this hypothesis suggests that bacterial and fungal products may act as adjuvants to S proteins and may also explain why S proteins alone are insufficient to induce neuroinflammation in neonates.

Source: Tatsuro Nobutoki. Long-term neurological implications of severe acute respiratory syndrome coronavirus 2 infections in neonates: Innate immune memory and chronic neuroinflammation. Medical Hypotheses, Volume 181, December 2023, 111204 https://www.sciencedirect.com/science/article/pii/S0306987723002001 (Full text)