Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study, 2023, Li et al

(SARS-1)

Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study
Open Access: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00061-5/fulltext
Published: February 27, 2023
DOI: https://doi.org/10.1016/j.eclinm.2023.101884

Background
We aimed to characterise the long-term health outcomes of survivors of severe acute respiratory syndrome (SARS) and determine their recovery status and possible immunological basis.

Methods
We performed a clinical observational study on 14 health workers who survived SARS coronavirus infection between Apr 20, 2003 and Jun 6, 2003 in Haihe Hospital (Tianjin, China). Eighteen years after discharge, SARS survivors were interviewed using questionnaires on symptoms and quality of life, and received physical examination, laboratory tests, pulmonary function tests, arterial blood gas analysis, and chest imaging. Plasma samples were collected for metabolomic, proteomic, and single-cell transcriptomic analyses. The health outcomes were compared 18 and 12 years after discharge. Control individuals were also health workers from the same hospital but did not infect with SARS coronavirus.

Findings
Fatigue was the most common symptom in SARS survivors 18 years after discharge, with osteoporosis and necrosis of the femoral head being the main sequelae. The respiratory function and hip function scores of the SARS survivors were significantly lower than those of the controls. Physical and social functioning at 18 years was improved compared to that after 12 years but still worse than the controls. Emotional and mental health were fully recovered. Lung lesions on CT scans remained consistent at 18 years, especially in the right upper lobe and left lower lobe lesions. Plasma multiomics analysis indicated an abnormal metabolism of amino acids and lipids, promoted host defense immune responses to bacteria and external stimuli, B-cell activation, and enhanced cytotoxicity of CD8+ T cells but impaired antigen presentation capacity of CD4+ T cells.

Interpretation
Although health outcomes continued to improve, our study suggested that SARS survivors still suffered from physical fatigue, osteoporosis, and necrosis of the femoral head 18 years after discharge, possibly related to plasma metabolic disorders and immunological alterations.

Funding
This study was funded by the Tianjin Haihe Hospital Science and Technology Fund (HHYY-202012) and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-063B, TJYXZDXK-067C).

 

https://www.frontiersin.org/articles/10.3389/fpsyg.2020.612366/full

Other Disorders
Chronic Fatigue
Chronic fatigue syndrome (CFS) is a complex neurological disorder associated with persistent, overwhelming fatigue that affects > 3% of the population in Western countries and is more prevalent in women (Griffith and Zarrouf, 2008). Diagnostic criteria include severe, persistent fatigue for at least 6 months, exclusion of other medical disorders, and observation of at least four minor symptoms, including impaired memory, nausea, extreme post-exertion fatigue, headaches, muscle pain, sore throat, and poor sleep (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome et al., 2015). There remains a lack of treatment and diagnostics tools for CFS, although glucocorticoids have been used (McKenzie et al., 2000). Bone loss and increased fracture risk have been reported in individuals with CFS, independent of glucocorticoid use. Hoskin et al. found that hip BMD was approximately 7% lower in women with CFS (Hoskin et al., 2006). A prospective study reported a 1.16-fold increased risk of fracture in the CFS cohort without osteoporosis compared to the non-CFS cohort (Chen C.-S. et al., 2014). However, no mechanistic insights were provided in these studies. Other studies have reported that IGF-1 levels are altered in CFS patients (Buchwald et al., 1996; Berwaerts et al., 1998; Cleare et al., 2000; Nijs et al., 2003). IGF-1 is essential for osteoblast proliferation, thus impaired secretion could lead to bone loss. Studies are needed to further characterize those CFS patients with low serum IGF-1 to determine if these subgroups have increased fracture risk compared to CFS patients with normal or high levels of IGF-1. High prevalence of mycoplasma infections has also been reported in CFS patients (Choppa et al., 1998; Nasralla et al., 1999), which can stimulate macrophage activation and release of pro-inflammatory cytokines that enhance osteoclast activity. M. fermentans has been shown to produce 2-kDa macrophage-activating lipopeptide (MALP-2), which stimulates macrophages and bone resorption in a dose-dependent manner and is increased with CFS (Piec et al., 1999). Thus, chronic fatigue may induce bone loss or increase fracture risk through increased inflammation and/or dysregulation of growth factors.