Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study

Abstract:

Background: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort.

Methods: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found.

Results: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients.

Conclusions: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.

Source: Cornelissen MEB, Bloemsma LD, Vaes AW, Baalbaki N, Deng Q, Beijers RJHCG, Noij LCE, Houweling L, Bazdar S, Spruit MA, Maitland-van der Zee AH; on behalf of the P4O2 Consortium. Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study. J Transl Med. 2024 Feb 21;22(1):191. doi: 10.1186/s12967-024-04979-1. PMID: 38383493. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-04979-1 (Full text)

Fatiguing illness among employees in three large state office buildings, California, 1993: was there an outbreak?

Abstract:

The objective was to determine if a cluster of chronic fatigue syndrome (CFS)-like illness had occurred among employees in two large state office buildings in northern California, and to identify risk factors for and features of fatiguing illness in this population.

DESIGN: case-control study.

POPULATION AND SETTING: Over 3300 current employees in two state office buildings and employees in a comparable “control” building. Information was collected on demographic and occupational variables, the occurrence of fatiguing illness for at least one month in the previous year, and the presence of 36 symptoms. A total of 3312 (82%) of 4035 employees returned questionnaires. Overall, 618 (18.7%) persons reported fatigue lasting at least one month; including 382 (11.5%) with fatigue of at least six months’ duration and 75 (2.3%) with symptoms compatible with a CFS-like illness.

Independent risk factors for fatigue lasting one month or longer were found to be Native American ethnicity (OR 2.4, CI 1.1,5.3), Hispanic ethnicity (OR 1.7, CI 1.3,2.3), female sex (OR 1.5, CI 1.2,1.9), gross household incomes of less than $50,000 (OR 1.3, CI 1.1,1.6), and less than a college education (OR 1.3, CI 1.1,1.6). Similar risks were observed for persons who reported fatigue lasting six months or longer. Female sex (OR 3.2, CI 1.7, 6.4) was the only independent risk factor found for those persons classified as having a CFS-like illness. Case prevalence rates for all three categories of fatigue, as determined by multivariate analysis, were not significantly different among buildings.

Despite finding a substantial number of employees with fatiguing illness in the two state office buildings, the prevalence was not significantly different than that for a comparable control building. Previously unidentified risk factors for fatigue of at least one month and at least six months identified in this population included Hispanic ethnicity, not having completed college, and income below $50,000.

 

Source: Shefer A, Dobbins JG, Fukuda K, Steele L, Koo D, Nisenbaum R, Rutherford GW. Fatiguing illness among employees in three large state office buildings, California, 1993: was there an outbreak? J Psychiatr Res. 1997 Jan-Feb;31(1):31-43. http://www.ncbi.nlm.nih.gov/pubmed/9201645

 

An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome

Abstract:

We surveyed households in four rural Michigan communities to confirm a reported cluster of cases resembling chronic fatigue syndrome (CFS) and to study the epidemiology of fatigue in a rural area. Data were collected from 1698 households. We did not confirm the reported cluster. The prevalence of households containing at least one fatigued person was similar between communities thought to harbor the cluster and communities selected for comparison. Symptoms and features of generic forms of fatigue were very similar to those often attributed to CFS.

 

Source: Fukuda K, Dobbins JG, Wilson LJ, Dunn RA, Wilcox K, Smallwood D. An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):19-29. http://www.ncbi.nlm.nih.gov/pubmed/9201644

 

A cluster of cases of chronic fatigue and chronic fatigue syndrome: clinical and immunologic studies

Chronic fatigue syndrome (CFS) is characterized by unexplained, persistent fatigue and other symptoms including arthralgias, myalgias, cognitive impairment, and depression [1, 2]. It has been postulated that infectious agents play a role in both sporadic cases and clustered cases of CFS [3- 5].

We were notified of a cluster of CFS cases that occurred in a women’s residential facility; these cases were associated with an influenza-like outbreak in February 1990. We conducted a study of these events in 1993. Between 1990 and 1993,36 women had lived in the facility. Sixteen of these residents reported fatigue that lasted more than or equal to1 month during the 3-year study interval. Two of the residents who entered the facility before 1990 already had fatigue. Five residents stated that the onset of fatigue corresponded to the outbreak of the influenza-like illness. Nine women described no temporal relationship between their fatigue and the “flu” outbreak. The fatigue resolved in two of these nine women after several weeks, while it persisted in the other seven. Evaluations were performed for these seven residents, and diagnoses including lupus, ulcerative colitis, or hyperparathyroidism were considered for three, but no cause for the fatigue was established for the other four.

You can read the rest of this article here: http://cid.oxfordjournals.org/content/23/2/408.long

 

Source: Levine PH, Dale JK, Benson-Grigg E, Fritz S, Grufferman S, Straus SE. A cluster of cases of chronic fatigue and chronic fatigue syndrome: clinical and immunologic studies. Clin Infect Dis. 1996 Aug;23(2):408-9. http://www.ncbi.nlm.nih.gov/pubmed/8842294

 

Chronic fatigue syndrome

SIR,

Dr Anthony David and colleagues (1) cite our paper (2) as one that makes inflated claims about the chtionic fatigue syndrome.

We first reported retrospectively an association between antibodies to coxsackie virus B and a group of symptoms similar to those previously described as myalgic encephalomyelitis. (3) We were faced with an ever increasing clinical problem of which we had little understanding, and the prospective investigation of coxsackie virus B antibody titres in these patients seemed a reasonable step forward. No widely accepted definition of the chronic fatigue syndrome existed in 1983, and we did not attempt to define it. We approached the problem from the opposite direction in that we had a definable test and we tried to show what happened to the results of this test in a group of ill patients.

Since 1983 much research into this syndrome has been carried out. It has taken a long time for a consensus to be agreed defining the syndrome. We believe that today’s definition that the syndrome cannot be diagnosed before six months has elapsed is acceptable. In our study 72% of our patients were still unwell six months into the illness.

The comparison made by Dr David and colleagues of their paper with ours is invalid. They questioned 611 general practice attenders whereas we reported on a group of 140 patients presenting over six months with what we believe to be the same illness.

In retrospect we think that what we observed was the slow spread of an infective agent through our town in 1983 and through neighbouring towns in our district in 1984 and 1985. The clinical syndrome coincided with a rise in the prevalence of coxsackie virus B antibodies in the general population from 10-12% in 1973-84 (we found 25% in 1983) to 55% in 1985-6. (4) Since then our clinical impression has been one of a return to normal; we see occasional new cases but not as many as in 1983.

The prevalence of this condition seems to depend on the activity of an infective agent of some kind, be it viral or otherwise, in the area of study at the time, and further research is made difficult by the wide fluctuations of prevalence that will be found from place to place and from time to time.

~B D CALDER

~P J WARNOCK Helensburgh G84 8BW

1 David A, Pelosi A, McDonald E, et al. Tired, weak, or in need of rest: fatigue among general practice attenders. BMJ 1990;301:1199-202. (24 November.)

2 Calder BD, Warnock PJ, McCartney RA, Bell EJ. Coxsackie B viruses and post-viral syndrome J R Coll Gen Pract 1987;37: 11-4.

3 Calder BD, Warnock PJ. Coxsackie B infections in Scottish general practice. J R Coll Gen Pract 1984;34:15-9.

4 Miller NA, Carmichael HA, Calder BD, et al. Antibody to coxsackie B virus in diagnosing postviral fatigue syndrome. BMJ (in press).

 

Source: B D Calder and P J Warnock. Chronic fatigue syndrome. BMJ. 1991 Jan 19; 302(6769): 181. PMCID: PMC1668832 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1668832/

 

Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases

Abstract:

After seven pediatric cases of chronic fatigue syndrome (CFS) were diagnosed in a farming community in upstate New York, a questionnaire regarding symptoms and potential risk factors of CFS was distributed to all students enrolled in the same school district.

Twenty-one students with symptoms of CFS were identified. Two controls per case matched for age and sex were randomly selected from questionnaire respondents. Health status was verified for all subjects by telephone, and diagnosis of CFS was confirmed by a physician.

Information was collected on the following factors: symptoms of CFS among other family members; history of allergy/asthma; consumption of raw milk, raw eggs, raw cheese, or raw meat; water supply; exposure to animals; home heating source; proximity to farmland/orchards; tick bite; blood transfusion; camping; and appendicitis.

Logistic-regression analyses indicated that the best model (characterized by symptoms among other family members, recent ingestion of raw milk, and history of allergy/asthma) produced significant estimates of relative risk (P less than .05) of 35.9, 44.3, and 23.3, respectively, for the three factors (corrections were made for the effect of the other covariates).

These data suggest that a combination of host and environmental factors, including an infectious agent or agents, are involved in the etiology of CFS.

 

Source: Bell KM, Cookfair D, Bell DS, Reese P, Cooper L. Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S32-8. http://www.ncbi.nlm.nih.gov/pubmed/2020801