Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome

Abstract:

Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome.

Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis.

Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status.

Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.

Source: Ferreira JC, Moreira TCL, de Araújo AL, Imamura M, Damiano RF, Garcia ML, Sawamura MV, Pinna FR, Guedes BF, Gonçalves FAR, Mancini M, Burdmann EA, da Silva Filho DF, Polizel JL, Bento RF, Rocha V, Nitrini R, de Souza HP, Levin AS, Kallas EG, Forlenza OV, Busatto GF, Batistella LR, de Carvalho CRR, Mauad T, Gouveia N; HCFMUSP COVID-19 Study Group. Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome. J Glob Health. 2022 Aug 9;12:05029. doi: 10.7189/jogh.12.05029. PMID: 35939273. https://jogh.org/2022/jogh-12-05029 (Full text)

Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building

Abstract:

Introduction: In 2010, dampness damage in a single-family house caused a massive mold infestation. In the further course, the 5 family members developed severe health problems. This report investigates the extent and cause of the water damage. In addition, the various visible fungal infestations were analyzed in a specialized laboratory.

Results: Due to building construction errors, starting from the basement, an increased moisture penetration of the residential building was detected. Within 2 years, massive mold infestation occurred. In 2016, the following species were detected: Cladosporium sphaerospermum, Chaetomium globosum, Penicillium chrysogenum, Scopularis brevicaulis, Acremonium furculum, A. charticola and A. sclerotigenum, Trichomonascus apis Aspergillus versicolor and Debaryomyces hansenii. Additionally, different black molds were macroscopically detected. The severity of the disease process varied, probably due to the different daily exposure of the family members, and possibly influenced by age. The children presented acute episodes with nocturnal cough, associated with sleep disturbances and respiratory infections with severe rhinitis. In addition, general fatigue was noticeable. The course of the disease was complicated by recurrent nightly nosebleeds. The mother developed a much more severe course as chronic fatigue syndrome. Additionally, the following continuous complaints occurred: sore throat and headache, nocturnal irritable cough, chronic rhinitis, difficulty concentrating, increasing forgetfulness and word-finding disorders, cognitive impairment with reduced short-term memory, extremely dry eyes with red sclerae, morning stiffness, dyspnea, disturbed temperature regulation (chills), increased feeling of thirst, and menstrual disorders. The father’s building-related illness (BRI) was comparatively mild due to much lower exposure, with nocturnal irritable cough, rhinitis, and marked fatigue. In 2018, after moving out of the house, the father was symptom-free after 2 weeks, the three children after 6 months, but the mother only after 18 months.

Discussion: The symptoms are consistent with reports from the literature, according to which fatigue, sleep disturbances, lack of concentration and headache as well as recurrent infections of the upper respiratory tract are caused by microbial volatile organic compounds (MVOCs) released by molds. The association with recurrent nosebleeds in childhood has not been described in this form before.

Conclusion: Since in all family members complete remission of symptoms occurred after cessation of the 6-year exposure, there is no doubt that the BRI was caused by the massive mold infestation.

Source: Kramer A, Wichelhaus TA, Kempf V, Hogardt M, Zacharowski K. Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building. GMS Hyg Infect Control. 2021 Dec 7;16:Doc32. doi: 10.3205/dgkh000403. PMID: 34956824; PMCID: PMC8662741. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662741/ (Full text)

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS.

Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS.

This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

Source: Bjørklund G, Dadar M, Pivina L, Doşa MD, Semenova Y, Maes M. Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome [published online ahead of print, 2020 Aug 6]. Mol Neurobiol. 2020;10.1007/s12035-020-01939-w. doi:10.1007/s12035-020-01939-w  https://pubmed.ncbi.nlm.nih.gov/32761353/

Neuroinflammation disorders exacerbated by environmental stressors

Abstract:

Neuroinflammation is a condition characterized by the elaboration of proinflammatory mediators within the central nervous system. Neuroinflammation has emerged as a dominant theme in contemporary neuroscience due to its association with neurodegenerative disease states such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

While neuroinflammation often is associated with damage to the CNS, it also can occur in the absence of neurodegeneration, e.g., in association with systemic infection. The “acute phase” inflammatory response to tissue injury or infections instigates neuroinflammation-driven “sickness behavior,” i.e. a constellation of symptoms characterized by loss of appetite, fever, muscle pain, fatigue and cognitive problems. Typically, sickness behavior accompanies an inflammatory response that resolves quickly and serves to restore the body to homeostasis. However, recurring and sometimes chronic sickness behavior disorders can occur in the absence of an underlying cause or attendant neuropathology.

Here, we review myalgic enchepalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Illness (GWI), and chemobrain as examples of such disorders and propose that they can be exacerbated and perhaps initiated by a variety of environmental stressors. Diverse environmental stressors may disrupt the hypothalamic pituitary adrenal (HPA) axis and contribute to the degree and duration of a variety of neuroinflammation-driven diseases.

Source: O’Callaghan JP, Miller DB. Neuroinflammation disorders exacerbated by environmental stressors. Metabolism. 2019 Nov;100S:153951. doi: 10.1016/j.metabol.2019.153951. https://www.ncbi.nlm.nih.gov/pubmed/31610852

Mirrored symptoms in mother and child with chronic fatigue syndrome

Abstract:

OBJECTIVE: Our aim with this study was to assess the relation between chronic fatigue syndrome in adolescents and fatigue and associated symptoms in their fathers and mothers, more specifically the presence of chronic fatigue syndrome-like symptoms and psychologic distress.

METHOD: In this cross-sectional study, 40 adolescents with chronic fatigue syndrome according to the Centers for Disease Control and Prevention criteria were compared with 36 healthy control subjects and their respective parents. Questionnaires regarding fatigue (Checklist Individual Strength), fatigue-associated symptoms, and psychopathology (Symptom Checklist-90) were applied to the children and their parents.

RESULTS: Psychologic distress in the mother corresponds with an adjusted odds ratio of 5.6 for the presence of CFS in the child. The presence of fatigue in the mother and dimensional assessment of fatigue with the Checklist Individual Strength revealed odds ratios of, respectively, 5.29 and 2.86 for the presence of chronic fatigue syndrome in the child. An increase of 1 SD of the hours spent by the working mother outside the home reduced the risk for chronic fatigue syndrome in their child with 61%. The fathers did not show any risk indicator for chronic fatigue syndrome in their child.

CONCLUSIONS: Mothers of adolescents with chronic fatigue syndrome exhibit fatigue and psychologic symptoms similar to their child in contrast with the fathers. The striking difference between the absent association in fathers and the evident association in mothers suggests that the shared symptom complex of mother and child is the result of an interplay between genetic vulnerability and environmental factors.

Comment in: Potential polygenic influences on chronic fatigue syndrome. [Pediatrics. 2006]

 

Source: van de Putte EM, van Doornen LJ, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Mirrored symptoms in mother and child with chronic fatigue syndrome. Pediatrics. 2006 Jun;117(6):2074-9. https://www.ncbi.nlm.nih.gov/pubmed/16740850

 

The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations

Abstract:

This monograph of peer-reviewed articles is based on presentations at the conference “Environmental Factors in Medically Unexplained Physical Symptoms and Related Syndromes” held 10-12 January 2001 in Piscataway, New Jersey, USA. The purpose of the conference was to determine research priorities for elucidating the role of environmental factors in medically unexplained symptoms and symptom syndromes. These include conditions such as chronic fatigue syndrome, multiple chemical sensitivities, sick building syndrome, Gulf War illness, and the like. Approximately 1 1/2 days were devoted to plenary talks and 1 day was devoted to break-out sessions to discuss epidemiologic, psychosocial, and experimental research. Recommendations were made for a series of epidemiologic, psychosocial, and experimental research approaches, with acknowledgment that nosology issues are clearly fundamental to advancing understanding of these conditions.

 

Source: Kipen HM, Fiedler N. The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations. Environ Health Perspect. 2002 Aug;110 Suppl 4:591-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241210/ (Full article)

 

A twin study of the etiology of prolonged fatigue and immune activation

Abstract:

Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors.

Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwin-crosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation.

By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49-0.69 versus 0.42-0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = -0.07 to -0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation.

PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.

 

Source: Hickie IB, Bansal AS, Kirk KM, Lloyd AR, Martin NG. A twin study of the etiology of prolonged fatigue and immune activation. Twin Res. 2001 Apr;4(2):94-102. http://www.ncbi.nlm.nih.gov/pubmed/11665341