Tag: post-infectious sequelae

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments

Abstract:

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address.

In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.

Source: Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021 May 22:1-18. doi: 10.1080/23744235.2021.1924397. Epub ahead of print. PMID: 34024217. https://pubmed.ncbi.nlm.nih.gov/34024217/

Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data

Abstract:

Whilst the entire world is battling the second wave of COVID-19, a substantial proportion of patients who have suffered from the condition in the past months are reporting symptoms that last for months after recovery, i. e., long-term COVID-19 symptoms. We aimed to assess the current evidence on the long-term symptoms in COVID-19 patients. We did a systematic review on PubMed, Web of Science, EMBASE, and Google Scholar from database inception to February 15, 2021, for studies on long-term COVID-19 symptoms.

We included all type of papers that reported at least one long-term COVID-19 symptom. We screened studies using a standardized data collection form and pooled data from published studies. Cohort cross-sectional, case-report, cases-series, case-control studies, and review were graded using specific quality assessment tools. Of 11,361 publications found following our initial search we assessed 218 full-text articles, of which 145 met all selection criteria. We found that 20.70% of reports on long-term COVID-19 symptoms were on abnormal lung functions, 24.13% on neurologic complaints and olfactory dysfunctions, and 55.17% on specific widespread symptoms, mainly chronic fatigue, and pain.

Despite the relatively high heterogeneity of the reviewed studies, our findings highlighted that a noteworthy proportion of patients who have suffered from SARS-CoV-2 infection present a “post-COVID syndrome.” The multifaceted understanding of all aspects of the COVID-19 pandemic, including these long-term symptoms, will allow us to respond to all the global health challenges, thus paving the way to a stronger public health.

Source: Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data. Front Med (Lausanne). 2021 May 4;8:653516. doi: 10.3389/fmed.2021.653516. PMID: 34017846; PMCID: PMC8129035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129035/ (Full text)

Our Evolving Understanding of ME/CFS

Abstract:

The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul- or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the ‘hallmark’ symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes.

We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.

Source: Friedman KJ, Murovska M, Pheby DFH, Zalewski P. Our Evolving Understanding of ME/CFS. Medicina (Kaunas). 2021 Feb 26;57(3):200. doi: 10.3390/medicina57030200. PMID: 33652622. https://www.mdpi.com/1648-9144/57/3/200 (Full text)

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Abstract:

Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term “long COVID”. A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition.

In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in “brain fog”. Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome).

There are similarities between chronic fatigue syndrome and the “brain fog” described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.

Source: Stefano GB. Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID. Med Sci Monit. 2021 Feb 26;27:e931447. doi: 10.12659/MSM.931447. PMID: 33633106; PMCID: PMC7924007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924007/ (Full text)

Association between chronic fatigue syndrome and suicidality among survivors of Middle East respiratory syndrome over a 2-year follow-up period

Abstract:

Suicide is an important public health issue during the current pandemic of emerging infectious diseases (EIDs). In EIDs, various symptoms persist even after recovery, and chronic fatigue is among those that are commonly reported. The aim of this study was to examine the effects of chronic fatigue syndrome on suicidality during the recovery phase among survivors of Middle East respiratory syndrome (MERS). MERS survivors were recruited from five centers and prospectively followed up for 2 years. In total, 63 participants were registered at 12 months (T1), of whom 53 and 50 completed the assessments at 18 months (T2) and 24 months (T3), respectively. Suicidality and chronic fatigue were evaluated using the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Fatigue Severity Scale (FSS), respectively.

We analyzed the relationship between chronic fatigue and suicidality during the follow-up period using the generalized estimating equation (GEE). The suicidality rates were 22.2% (n = 14), 15.1% (n = 8), and 10.0% (n = 5) at T1-T3, respectively. Of the 63 participants, 29 had chronic fatigue syndrome at T1. The group that reported chronic fatigue syndrome at T1 was more likely to experience suicidality during the 2-year follow-up than the group that reported otherwise (RR: 7.5, 95% CI: 2.4-23.1). This association was present even after adjusting for potential confounders (RR: 7.6, 95% CI: 2.2-26.0). Chronic fatigue syndrome and suicide risk among emerging infectious disease (EID) survivors should be acknowledged, and effective interventions must be developed.

Source: Ahn SH, Kim JL, Kim JR, Lee SH, Yim HW, Jeong H, Chae JH, Park HY, Lee JJ, Lee H. Association between chronic fatigue syndrome and suicidality among survivors of Middle East respiratory syndrome over a 2-year follow-up period. J Psychiatr Res. 2021 Feb 17;137:1-6. doi: 10.1016/j.jpsychires.2021.02.029. Epub ahead of print. PMID: 33631632; PMCID: PMC7888998. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888998/  (Full text)

Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island

Abstract:

Prolonged fatigue is increasingly reported among chikungunya virus (CHIKV)-infected populations. We investigated the relationships between CHIKV exposure, long-lasting rheumatic musculoskeletal pain (LRMSP) and chronic fatigue. 1094 participants (512 CHIKV seropositive and 582 seronegative) of the TELECHIK population-based cohort were analysed considering the duration of the manifestations throughout an average 2-year follow-up.

Weighted prevalence rates and prevalence ratios for LRMSP, idiopathic chronic fatigue (ICF), and chronic fatigue syndrome (CFS)-like illness, both latter syndromes adapted from Centers for Disease Control (CDC)-1994/Fukuda criteria, were compared. Population attributable fractions (PAF) were estimated to assess the contribution of CHIKV infection to each of the three phenotypes.

Among 362 adult subjects who had reported either rheumatic pain or fatigue at the onset of the infection, weighted prevalence rates of LRMSP, ICF and CFS-like illness were respectively of 32.9%, 38.7% and 23.9%, and of 8.7%, 8.5% and 7.4% among initially asymptomatic peers (P < 0.01, respectively). Each of the three outcomes was highly attributable to chikungunya (PAF of 43.2%, 36.2% and 41.0%, respectively).

In the sub-cohort of CHIKV-infected subjects, LRMSP, ICF and CFS-like illness, which overlapped in 70%, accounted for 53% of the chronic manifestations. In addition to rheumatic disease, chronic fatigue could be considered in caring for patients with chronic chikungunya disease.

Source: Duvignaud A, Fianu A, Bertolotti A, Jaubert J, Michault A, Poubeau P, Fred A, Méchain M, Gaüzère BA, Favier F, Malvy D, Gérardin P. Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island. Epidemiol Infect. 2018 Feb 28:1-9. doi: 10.1017/S0950268818000031. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29486812

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome

Abstract:

BACKGROUND: A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes.

METHODS: 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry.

RESULTS: In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen.

CONCLUSION: Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

 

Source: Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, Bødtker JE, Hausken T, Langeland N. Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. BMC Infect Dis. 2012 Oct 14;12:258. doi: 10.1186/1471-2334-12-258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553045/ (Full article)

 

Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway

Abstract:

BACKGROUND: We aimed to compare patients reporting acute infection with those reporting no infection at onset of chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: This study includes 873 patients with CFS referred to a tertiary centre on average 4.8 years after symptom onset. Assessment was by both observer query and self-reports. Antibody analyses against infectious agents including Epstein-Barr virus and enterovirus were performed in a majority of patients.

RESULTS: Females comprised 75.3% of the patient group, and the mean age was 33 years. Initial infection was reported by 77%. There was no difference as to antibody analyses. Logistic regression showed that initial infection was independently associated with acute onset of fatigue, improvement of fatigue at referral, and the following symptoms at referral: fever, tender lymph nodes, and myalgia.

CONCLUSION: CFS patients with initial infection as a precipitating factor more often report acute onset of fatigue, more frequent accompanying symptoms, and more frequent improvement on referral than do patients without initial infection.

 

Source: Naess H, Sundal E, Myhr KM, Nyland HI. Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway. In Vivo. 2010 Mar-Apr;24(2):185-8. https://www.ncbi.nlm.nih.gov/pubmed/20363992

 

Neuropsychiatric sequelae of Nipah virus encephalitis

Abstract:

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome.

Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

 

Source: Ng BY, Lim CC, Yeoh A, Lee WL. Neuropsychiatric sequelae of Nipah virus encephalitis. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):500-4. http://www.ncbi.nlm.nih.gov/pubmed/15616178

 

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort

Abstract:

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue.

AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure.

DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever.

METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests.

RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004).

DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

Comment in: Q fever: still a mysterious disease. [QJM. 2002]

 

Source: Wildman MJ, Smith EG, Groves J, Beattie JM, Caul EO, Ayres JG. Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort. QJM. 2002 Aug;95(8):527-38. http://qjmed.oxfordjournals.org/content/95/8/527.long (Full article)