Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed.
Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males.
After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.
Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, Navarro-Pardo E, Gómez-Mayordomo V, Cuadrado ML, Arias-Navalón JA, Cigarán-Méndez M, Hernández-Barrera V, Arendt-Nielsen L. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022 Jan 14;11(2):413. doi: 10.3390/jcm11020413. PMID: 35054108; PMCID: PMC8778106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778106/ (Full text)
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Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Abstract:

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50).

At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months).

In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275).

Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

 

Source: Kerr JR, Barah F, Mattey DL, Laing I, Hopkins SJ, Hutchinson IV, Tyrrell DA. Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol. 2001 Dec;82(Pt 12):3011-9. http://www.ncbi.nlm.nih.gov/pubmed/11714978

 

Prevalence of chronic fatigue syndrome in 4 family practices in Leiden

Abstract:

OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) in general practice.

DESIGN: Descriptive.

SETTING: General practice and primary health care centres in Leyden region, the Netherlands.

METHOD: RNUH-LEO is a computerized database which contains the anonymous patient information of one general practice (with two practitioners) and four primary health care centres. The fourteen participating general practitioners were asked what International Classification of Primary Care (ICPC) code they used to indicate a patient with chronic fatigue or with CFS. With these codes and with the code for depression patients were selected from the database. It then was determined whether these patients met the criteria of CFS by Holmes et al.

RESULTS: The general practitioners used 10 codes. Including the code for depression a total of 601 patients were preselected from a total of 23,000 patients in the database. Based on the information from the patients’ records in the database, 42 of the preselected patients were selected who might fulfill the Holmes’ criteria of CFS. According to the patients’ own general practitioner, 25 of the 42 patients would fulfil the Holmes’ criteria. The men:women ratio was 1:5. The prevalence of CFS in the population surveyed was estimated to be at least 1.1 per 1,000 patients.

 

Source: Versluis RG, de Waal MW, Opmeer C, Petri H, Springer MP. Prevalence of chronic fatigue syndrome in 4 family practices in Leiden. Ned Tijdschr Geneeskd. 1997 Aug 2;141(31):1523-6. [Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/9543740

 

Prevalence of chronic fatigue syndrome and primary fibromyalgia syndrome in The Netherlands

Erratum in: Ned Tijdschr Geneeskd 1997 Sep 13;141(37):2686.

 

Abstract:

OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) and of primary fibromyalgia syndrome (PFS) in the Netherlands.

DESIGN: Questionnaire.

SETTING: Department of Medical Psychology, University Hospital Nijmegen, the Netherlands.

METHOD: A questionnaire was mailed to all the 6657 general practitioners in the Netherlands in order to inform them of the existence of CFS and to ask them if they had any CFS or PFS patients in their practices.

RESULTS: Sixty percent (n = 4027) of the general practitioners returned the questionnaire. Of all the general practitioners, 27% said they had no CFS patients, 23% said they had 1 CFS patient, while 21% had 2 CFS patients, and 29% said they had 3 or more CFS patients in their practice. Concerning PFS the results were 17% (no PFS patients), 18%, 18% and 47%, respectively. With a mean practice of 2486 patients per general practice, the estimated prevalence of CFS was 112 per 100,000 and that of PFS 157 per 100,000 persons. Of the CFS patients 81% were women and 55% were 25-44 years old; for PFS these figures were 87% and 48% respectively.

CONCLUSION: Extrapolation of the study results indicates that there are at least 17,000 CFS patients and 24,000 PFS patients in the Netherlands. The found prevalence is probably an under-estimation.

 

Source: Bazelmans E, Vercoulen JH, Galama JM, van Weel C, van der Meer JW, Bleijenberg G. Prevalence of chronic fatigue syndrome and primary fibromyalgia syndrome in The Netherlands. Ned Tijdschr Geneeskd. 1997 Aug 2;141(31):1520-3. [Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/9543739

 

Generalized anxiety disorder in chronic fatigue syndrome

Abstract:

A structured psychiatric interview, forming part of a global psychopathological approach, revealed higher prevalence rates of current and lifetime psychiatric disorders and a higher degree of psychiatric comorbidity in patients with chronic fatigue syndrome (CFS) than in a medical control group. In contrast to previous studies, a very high prevalence of generalized anxiety disorder (GAD) was found in CFS, characterized by an early onset and a high rate of psychiatric comorbidity.

It is postulated that GAD represents a susceptibility factor for the development of CFS. A significantly higher prevalence was also observed for the somatization disorder (SD) in the CFS group. Apart from a higher female-to-male ratio in fibromyalgia, no marked differences were observed in sociodemographic or illness-related features, or in psychiatric morbidity, between CFS patients with and without fibromyalgia. CFS patients with SD have a longer illness duration and a higher rate of psychiatric comorbidity.

These findings are consistent with the suggestion of Hickie et al. (1) that chronic fatigued subjects with SD should be distinguished from subjects with CFS.

 

Source: Fischler B, Cluydts R, De Gucht Y, Kaufman L, De Meirleir K. Generalized anxiety disorder in chronic fatigue syndrome. Acta Psychiatr Scand. 1997 May;95(5):405-13. http://www.ncbi.nlm.nih.gov/pubmed/9197905

 

Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan

Abstract:

In order to clarify the epidemiological features of chronic fatigue syndrome (CFS), a nationwide survey was conducted using the Japanese version of the CDC Criteria prepared by the CFS Research Group of Japan. All clinical departments of internal medicine, pediatrics, psychiatry and neurology at university hospitals and at ordinary hospitals with 200 or more beds were surveyed.

Major results were as follows: (1) Period prevalence adjusted for response rate was 0.85 (0.63 for males and 1.02 for females) per 100,000 population during the year 1992; (2) Based on the first and final dates of hospital visits, the prevalences on January 1 of 1992 and 1993 were 0.40 and 0.60 per 100,000 population, respectively, suggesting an increasing trend; (3) Reported new cases during 1992 were 301, and the response adjusted-incidence was estimated to be 0.46 per 100,000 person-years; (4) The proportion of post-infectious CFS cases was 14.8% for both sexes, and tended to be slightly higher among females than males, but was not related to age. Three clusterings of two cases were reported.

 

Source: Minowa M, Jiamo M. Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan. J Epidemiol. 1996 Jun;6(2):75-80. https://www.jstage.jst.go.jp/article/jea1991/6/2/6_2_75/_pdf (Full article)

 

Chronic active Epstein-Barr virus infection in children in Japan

Abstract:

The patients with chronic active Epstein-Barr virus infection (CAEBV) in childhood in Japan are described. Among 39 registered cases, 20 patients were males and 19 were females. Unlike the X-linked lymphoproliferative syndrome, there was no hereditary background.

The incidence of hypersensitivity to mosquito bites was high (31.3%) as a past history. Most patients exhibited hepatomegaly (92.3%), splenomegaly (87.2%) and fever (84.6%). The incidence of absent anti-EB virus nuclear antigen titres was unexpectedly low (17.1%). Lymphoreticular disorders and cardiovascular diseases were major complications.

Twenty-four (61.5%) patients died 6 months to 8 years after the onset, mainly of hepatic failure (eight cases), cardiac failure (five cases), virus-associated haemophagocytic syndrome (three cases) and haematological malignancies (two cases). This study reveals the CAEBV in Japan has several clinical features and should be informative for the pathogenesis of EB virus.

 

Source: Ishihara S, Okada S, Wakiguchi H, Kurashige T, Morishima T, Kawa-Ha K. Chronic active Epstein-Barr virus infection in children in Japan. Acta Paediatr. 1995 Nov;84(11):1271-5. http://www.ncbi.nlm.nih.gov/pubmed/8580625

 

Chronic fatigue syndrome–51 cases in the Jikei University School of Medicine

Abstract:

Between April 1991 and August 1992, we diagnosed 51 cases of CFS who met definition of CFS designated by CDC, 1988. They are 41 female and 11 male, and 78% are women. At first visit, their ages are ranged from 16 to 64 years old, and approximately 45% is 20 to 30 years old.

In periods of illness from onset, 39.2% of the patients are in period of 6 month to 1 year, 19.6% within 2 years, and 15.6% within 3 years, respectively. The sufferer who have symptoms of CFS over 10 years long are in 6 cases.

Most of patients have already been examined by many other clinics and hospitals. They have been told as no abnormal medical condition, or often as neurosis, depressive state and autonomous imbalance etc.

Interesting things are trigger of CFS. 77.5% of patients have onset of flu-like symptom, including 5 cases of acute infectious mononucleosis. In many female patients, symptoms of CFS begun after hard work in addition to psychological factors. Specific laboratory results are not shown in CBC, urinalysis, biochemical studies and inflammatory markers. 6 cases have positive Rheumatoid factor and positive ANF are shown in 16 cases (31.3%).

Specific patterns of anti EBV antibodies are not shown. Lymphocyte subsets used by monoclonal antibodies are not specific. At the present, prognosis is good and 56.8% of CFS patients are generally improved. For severe cases, NSAID, Sulpiride, Amitryptiline and minor tranquilizer are used.

 

Source: Hashimoto N, Kuraishi Y, Yokose T, Tajima N, Mochio S, Shimizu M, Yokoyama J, Kobayashi N, Nohara A, Taniguchi I, et al. Chronic fatigue syndrome–51 cases in the Jikei University School of Medicine. Nihon Rinsho. 1992 Nov;50(11):2653-64. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287241

 

Prevalence of chronic fatigue syndrome in an Australian population

Abstract:

An epidemiological study was undertaken to provide the first reported estimate of the point prevalence of chronic fatigue syndrome in an Australian community.

After a pilot study in a separate location, the population of the Richmond Valley, New South Wales, was sampled using a structured case-finding technique, which included notification from local medical practitioners, the use of a screening questionnaire and standardised interviews conducted by a physician and psychiatrist. In addition, investigations were performed to exclude alternative diagnoses and to assess cell-mediated immunity.

Forty-two patients with chronic fatigue syndrome, with a female:male ratio of 1.3:1.0, were detected in a population of 114,000. The mean age at onset of symptoms was 28.6 years (SD, 12.3 years), and the median duration of symptoms from onset to sampling date was 30 months. The social status of the patients was distributed in accordance with that of the remainder of the population sampled, with no bias towards the middle or upper social classes. The disorder was causing considerable incapacity, with 43% of patients unable to attend school or work.

The conservative estimate from this study suggests a prevalence on June 30 1988 of 37.1 cases per 100,000 (95% confidence interval [CI], 26.8-50.2). Chronic fatigue syndrome is an important disorder in this Australian community that affects young individuals from all social classes and causes considerable ill health and disability.

 

Source:  Lloyd AR, Hickie I, Boughton CR, Spencer O, Wakefield D. Prevalence of chronic fatigue syndrome in an Australian population. Med J Aust. 1990 Nov 5;153(9):522-8. http://www.ncbi.nlm.nih.gov/pubmed/2233474