How post-infection status could lead to the increasing risks of chronic fatigue syndrome and the potential mechanisms: A 17-year population based Cohort study

Abstract:

Background: Serological studies have suggested that viruses and atypical pathogens are associated with CFS, but no study has focused on typical and common pathogens. This study aims to assess the association of infections with a variety of common pathogens with the risk of CFS and provide evidence for the hypothesis that infection triggers CFS.

Methods: The nested case-control study identified 2,000,000 adult patients from a nationwide population-based health insurance claims database from January 1, 2000, to December 31, 2017. Each case with a diagnosis of infection by pathogens was matched with one control using a propensity score. Patients with more than one potential pathogen, younger than 20 years old, or with a history of CFS or infection with certain pathogens before the index date were excluded. Univariate and multivariate Cox proportional hazard models were applied to estimate the HR, aHR, and corresponding 95% CI. The multivariate analysis had adjustments for age, sex, comorbidities, and medication confounders.

Results: A total of 395,811 cases with 1: 1 matched controls were included (58.2% female; mean age [standard deviation], 44.15 [17.02]). Among these, the aHR of the pathogen cohort was 1.5 (95% CI, 1.47 to 1.54). Pathogens were positively correlated with CFS, including influenza, candida and others.

Conclusion: The findings of this study demonstrate the association between CFS and infection with common pathogens, including bacteria, virus and fungi.

Source: Hsun Chang; Chien-Feng Kuo; Teng-Shun Yu; Liang-Yin Ke; Chung-Lieh Hung; Shin-Yi Tsai. How post-infection status could lead to the increasing risks of chronic fatigue syndrome and the potential mechanisms: A 17-year population based Cohort study. Research Square, August 30, 2023. https://assets.researchsquare.com/files/rs-3289981/v1/55890598-6f0d-4f73-a9f4-5349e07baac0.pdf (Full text)

Long COVID Complicated by Fatal Cytomegalovirus and Aspergillus Infection of the Lungs: An Autopsy Case Report

Abstract:

After the acute phase of COVID-19, some patients develop long COVID. This term is used for a variety of conditions with a complex, yet not fully elucidated etiology, likely including the prolonged persistence of the virus in the organism and progression to lung fibrosis. We present a unique autopsy case of a patient with severe COVID-19 with prolonged viral persistence who developed interstitial lung fibrosis complicated by a fatal combination of cytomegalovirus and Aspergillus infection. SARS-CoV-2 virus was detected at autopsy in the lungs more than two months after the acute infection, although tests from the nasopharynx were negative.
Immune dysregulation after COVID-19 and the administration of corticoid therapy created favorable conditions for the cytomegalovirus and Aspergillus infection that were uncovered at autopsy. These pathogens may represent a risk for opportunistic infections, complicating not only the acute coronavirus infection but also long COVID, as was documented in the presented case.
Source:Krivosikova L, Kuracinova T, Martanovic P, Hyblova M, Kaluzay J, Uhrinova A, Janega P, Babal P. Long COVID Complicated by Fatal Cytomegalovirus and Aspergillus Infection of the Lungs: An Autopsy Case Report. Viruses. 2023; 15(9):1810. https://doi.org/10.3390/v15091810 https://www.mdpi.com/1999-4915/15/9/1810 (Full text)

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Abstract:

Long COVID, a type of Post-Acute Sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 could be exacerbated by microbial translocation (from gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown.

We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation – measured as β-glucan, a fungal cell wall polysaccharide – in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling.

Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared to plasma from negative controls. This higher NF-κB signaling was abrogated by Piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Source: Giron LB, Peluso MJ, Ding J, Kenny G, Zilberstein NF, Koshy J, Hong KY, Rasmussen H, Miller GE, Bishehsari F, Balk RA, Moy JN, Hoh R, Lu S, Goldman AR, Tang HY, Yee BC, Chenna A, Winslow JW, Petropoulos CJ, Kelly JD, Wasse H, Martin JN, Liu Q, Keshavarzian A, Landay A, Deeks SG, Henrich TJ, Abdel-Mohsen M. Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling. JCI Insight. 2022 Jun 21:e160989. doi: 10.1172/jci.insight.160989. Epub ahead of print. PMID: 35727635. https://pubmed.ncbi.nlm.nih.gov/35727635/

Chronic Fatigue Syndrome and Bone Marrow Defects of the Jaw – A Case Report on Additional Dental X-Ray Diagnostics with Ultrasound

Abstract:

Purpose: This paper aims to demonstrate the additional benefit of ultrasound in the diagnosis of chronic osteolysis and osteonecrosis (bone marrow defects) of the jaw shown in a clinical case report.

Patients and methods: A case of chronic fatigue syndrome (CFS) in a young man presenting the typical, ambiguous symptoms, which were accompanied by headaches and tinnitus. X-ray techniques, namely panoramic radiographs (OPG) and cone beam computed tomography (DVT/CBCT), failed to produce any remarkable findings of bone marrow defects (BMDJ) in the jawbone. However, the measurement of bone density using trans-alveolar ultrasound (TAU) indicated a possible bone marrow defect in the lower left jawbone.

Results: Surgery was undertaken at the conspicuous area. Additional to softened, ischemic, fatty tissue, a black area was revealed, which was surprisingly subsequently identified as aspergillosis by histopathological analysis. In addition, the excessive local RANTES/CCL5 expression found in the affected area confirmed the necessity for surgical debridement and additional findings of TAU.

Conclusion: In contrast to radiography, complementary TAU imaging of the BMDJ revealed chronic inflammatory signaling RANTES/CCL5 pathways and fungal colonization. This case report supports the need for additional diagnostic techniques beyond radiographic modalities, which can help to elucidate the diagnostic composition and knowledge of the bone manifestations of systemic diseases.

Source: Lechner J, Schick F. Chronic Fatigue Syndrome and Bone Marrow Defects of the Jaw – A Case Report on Additional Dental X-Ray Diagnostics with Ultrasound. Int Med Case Rep J. 2021 Apr 19;14:241-249. doi: 10.2147/IMCRJ.S306641. PMID: 33907473; PMCID: PMC8064682. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064682/ (Full text)

Adrenal histoplasmosis: a case series and review of the literature

Abstract:

Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis.

Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were “histoplasmosis” and “adrenal gland”.

Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome.

The onset of symptoms ranged from one to three months. Addison’s disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter.

The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years.

 

Source: Larbcharoensub N, Boonsakan P, Aroonroch R, Rochanawutanon M, Nitiyanant P, Phongkitkarun S, Poonvutikul S, Watcharananan SP, Ngarmukos C. Adrenal histoplasmosis: a case series and review of the literature. Southeast Asian J Trop Med Public Health. 2011 Jul;42(4):920-5. https://www.ncbi.nlm.nih.gov/pubmed/22299474