BREAKING NEWS! Study Find That COVID-19 Causes Decreased Plasma Cartilage Acidic Protein 1(CRTAC1) With Implications For Long COVID And Cancer!

COVID-19 News: In the midst of the COVID-19 pandemic, researchers around the world have tirelessly worked to understand the intricate dynamics of the virus and its impact on the human body. Among the many mysteries surrounding this novel coronavirus, a recent study conducted jointly by the University of Wisconsin-Madison, Albany Medical Center in New York, and the Morgridge Institute for Research in Madison, USA has shed light on a hitherto obscure protein known as Cartilage Acidic Protein 1 (CRTAC1). This new research has revealed a significant connection between COVID-19 and CRTAC1, a protein with implications for both acute infection severity and the enigmatic long COVID syndrome. The study delved into the potential ramifications for our understanding of COVID-19 and its lingering effects.


 
CRTAC1: An Enigmatic Protein
Cartilage Acidic Protein 1 (CRTAC1) is a protein produced by various cell types within the human body, with Type 2 alveolar epithelial (T2AE) cells being among its producers. Intriguingly, these T2AE cells are known to be susceptible to infection by the SARS-CoV-2 virus, which causes COVID-19. Prior to this study, CRTAC1 remained largely understudied, and its exact functions within the body remained obscure and was never covered in any COVID-19 studies or COVID-19 News reports.
 
Early Findings and Implications for COVID-19
The research conducted during the initial stages of the COVID-19 pandemic was instrumental in uncovering the association between CRTAC1 and the virus. Mass spectrometric studies revealed a notable decrease in plasma CRTAC1 levels in patients with COVID-19 who were experiencing deteriorating respiratory conditions. This decrease was further corroborated by studies utilizing tandem mass tagging, which compared patients with non-severe and severe COVID-19.

The intriguing connection between CRTAC1 and COVID-19 did not stop at mere correlation. The gene responsible for encoding human CRTAC1 was found to overlap with the gene GOLGA7B, which is essential for the palmitoylation of the SARS-CoV-2 spike protein and the production of infectious virus particles. This overlapping genetic relationship suggests a potential role for CRTAC1 in the viral life cycle.
 
Furthermore, the study identified T2AE cells as one of the primary producers of CRTAC1, and it was observed that the expression of CRTAC1 in these cells increased upon treatment with dexamethasone, a common medication for COVID-19.
 
Additionally, patients with idiopathic pulmonary fibrosis exhibited decreased CRTAC1 levels in both plasma and bronchoalveolar lavage, likely due to a loss of CRTAC1 expression by de-differentiated T2AE cells.
 
An Intriguing Interaction: CRTAC1 and CFP
One of the most noteworthy findings of this study was the discovery of an interaction between CRTAC1 and CFP (properdin of the alternate complement pathway). Properdin, a protein critical for the activation of the alternate complement pathway, was found to be decreased in patients with severe COVID-19 due to the intense activation of this pathway during the infection. The study demonstrated that soluble recombinant CRTAC1 interacts with insolubil ized recombinant CFP, suggesting that the decrease in CRTAC1 during severe COVID-19 may result from increased turnover due to complement pathway activation.
 
Understanding Long COVID
The implications of this research extend beyond acute COVID-19 infection. A significant finding was the persistent low levels of CRTAC1 in some patients even a year after hospitalization for severe COVID-19 or in those with long COVID who did not require hospitalization. This raises important questions about the nature and significance of reduced CRTAC1 concentrations in individuals experiencing long COVID symptoms.
 
Future Directions and Unanswered Questions
While this study has provided valuable insights into the relationship between COVID-19 and CRTAC1, several important questions remain unanswered. First, the study cohort consisted of patients hospitalized at the beginning of the pandemic, and the findings may not fully represent current severe COVID-19 cases with emerging SARS-CoV-2 variants and evolving treatment strategies.
 
Second, the study also identified low CRTAC1 concentrations in some non-COVID-19 patients with respiratory distress, emphasizing the need for further investigation into CRTAC1 levels in various respiratory conditions, such as influenza and other viral pneumonias.
 
Third, the subset of patients with long COVID who exhibit persistently low CRTAC1 levels requires more in-depth analysis to understand the underlying factors contributing to this phenomenon. Factors such as age, the nature and timing of the initial COVID-19 episode, and the presence of other conditions that affect CRTAC1 levels (e.g., osteoarthritis, idiopathic pulmonary fibrosis, or COPD) should be explored.
 
Lastly, the exact role of low plasma CRTAC1 in the pathophysiology of COVID-19 and its long-term effects remains a mystery. Animal models and genomic studies may provide insights into how the absence of CRTAC1 affects disease severity.
 
Cartilage Acidic Protein 1(CRTAC1) And Bladder Cancer
Past studies have shown that Cartilage Acidic Protein 1(CRTAC1) plays a role in inhibiting bladder cancer and decreased levels of it are associated with bladder cancer development and progression!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809913/


Plasma CRTAC1 concentrations determined by ELISA in different subject groups and relation to hospital day and clinical severity score. (a) The 20 healthy control subjects, 55 patients with COPD, and 128 hospitalized patients divided into groups without (n = 26, non-COVID, open circles) or with (n = 102, COVID, closed circles) COVID-19 and further divided into patients who were not (n = 10 + 51, respectively, non-ICU) or were (n = 16 + 51, respectively, ICU) in the intensive care unit at time of enrollment. ***p ≤ 0.001, *p ≤ 0.02 (t-test for pairwise comparison of COPD versus healthy, otherwise Tukey's multiple comparisons posttest). (b) CRTAC1 concentration versus day of hospitalization. The 128 patients divided into groups without (n = 26, open circles, dashed line) or with COVID-19 (n = 102, closed circles, solid line). Spearman rank correlation coefficient (rs) for COVID-19 = −0.10, p = 0.30; for non-COVID-19 rs = −0.28, p = 0.16, for all rs = −0.29, p = 0.0009. (c) CRTAC1 concentration in another set of hospitalized patients with COVID-19 (n = 5) who were sampled more than once with 3-day intervals. D: CRTAC1 concentration versus APACHE (acute physiological assessment and chronic health evaluation) II score. The 75 patients given an APACHEII score are divided into groups without (n = 17, open circles, dashed line) or with COVID-19 (n = 58, closed circles, solid line). rs for COVID-19 = −0.33, p = 0.01; for non-COVID-19 rs = −0.20, p = 0.44; for all rs = −0.30, p = 0.009. Band, range of healthy subjects (17.2–59.7 nM).

Conclusion
The study has uncovered a fascinating connection between CRTAC1 and COVID-19. This enigmatic protein, previously overlooked in medical research, may play a crucial role in both the acute infection's severity and the persistence of symptoms in long COVID and even give rise to bladder cancers.
 
As we continue to grapple with the ever-evolving COVID-19 pandemic, the findings of this study offer hope for a better understanding of the virus's impact on the human body. Further research is needed to unravel the intricacies of CRTAC1's involvement in COVID-19, shedding light on potential therapeutic interventions and avenues for alleviating the burden of long COVID.
 
The study findings were published in the peer reviewed journal: Physiological Reports.
https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15814
 
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