Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

Abstract:

The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.
Source: Amiama-Roig A, Pérez-Martínez L, Rodríguez Ledo P, Verdugo-Sivianes EM, Blanco J-R. Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID? Microorganisms. 2023; 11(3):713. https://doi.org/10.3390/microorganisms11030713 (Full text)

Long COVID-six months of prospective follow-up of changes in symptom profiles of non-hospitalised children and young people after SARS-CoV-2 testing: A national matched cohort study (The CLoCk) study

Abstract:

Background: Little is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no prospective follow-up to establish the pattern of symptoms over a 6-month time period.

Methods: A non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11-17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP.

Results: Three months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10-25% at testing to <3%. The prevalence of loss of smell declined from 21% to 5% at 3 months and 4% at 6 months. Prevalence of shortness of breath and tiredness also declined, but at a lower rate. Among test-negatives, the same common symptoms and trends were observed at lower prevalence’s. Importantly, in some instances (shortness of breath, tiredness) the overall prevalence of specific individual symptoms at 3 and 6 months was higher than at PCR-testing because these symptoms were reported in new cohorts of CYP who had not reported the specific individual symptom previously.

Conclusions: In CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.

Source: Stephenson T, Pinto Pereira SM, Nugawela MD, McOwat K, Simmons R, Chalder T, Ford T, Heyman I, Swann OV, Fox-Smith L, Rojas NK, Dalrymple E, Ladhani SN, Shafran R; CLoCk Consortium. Long COVID-six months of prospective follow-up of changes in symptom profiles of non-hospitalised children and young people after SARS-CoV-2 testing: A national matched cohort study (The CLoCk) study. PLoS One. 2023 Mar 6;18(3):e0277704. doi: 10.1371/journal.pone.0277704. PMID: 36877677; PMCID: PMC9987792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987792/ (Full text)

Understanding Long COVID Syndrome: An Up to the Minute Fret

Abstract:

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARSCoV-2) virus-induced corona virus disease 2019 (COVID-19) has had a global spread. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) rst emerged in Wuhan, China, in December 2019, and the infection spread rapidly across the world. The disease caused by the virus was named corona virus disease in 2019, and was declared a global pandemic by the World Health Organization (WHO) in March 2020. While the symptoms are mild or moderate in most patients, severe pneumonia can develop in 15%, and Acute Respiratory Distress Syndrome (ARDS), septic shock, and multiple organ failure in 5%. A comprehensive strategy for precautions includes hand washing, social distancing, isolation and mask-wearing. Besides, vaccines play an essential role in preventing the spread.

Long COVID or long-haul COVID (also known as post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS) is a condition characterized by long-term health problems persisting or appearing after the typical recovery period of COVID-19. Although studies into long COVID are under way, as of May 2022 there is no consensus on the definition of the term.

Long COVID has been described as having the potential to affect nearly every organ system, causing further conditions (sequelae) including respiratory system disorders, nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, musculoskeletal pain, and anemia. The most commonly reported symptoms of long COVID are fatigue and memory problems. Many other symptoms have also been reported, including malaise, headaches, shortness of breath, anosmia (loss of smell), parosmia (distorted smell), muscle weakness, low-grade fever, and cognitive dysfunction. Overall, it is considered by default to be a diagnosis of exclusion.

Source: Gomes, Richmond. (2023). Understanding Long COVID Syndrome: An Up to the Minute Fret. 04. 1-7.  https://www.researchgate.net/publication/369037934_Understanding_Long_COVID_Syndrome_An_Up_to_the_Minute_Fret (Full text)

Autoimmunity in Long Covid and POTS

Abstract:

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalised immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but prevalence with its supporting evidence is compelling.

In this review, we discuss the role of the autonomic nervous and immune systems in Covid and Long Covid and their potential influence on symptoms and clinical practice. Additionally, overlap with non-Covid autonomic dysfunction is considered. Understanding these new disorders can inform both neuro-immunology and Long Covid management.

Source: Fatema-Zahra El-Rhermoul, Artur Fedorowski, Philip Eardley, Patricia Taraborrelli, Dimitrios Panagopoulos, Richard Sutton, Phang Boon Lim, Melanie Dani, Autoimmunity in Long Covid and POTS, Oxford Open Immunology, 2023;, iqad002, https://doi.org/10.1093/oxfimm/iqad002 (Full text available as PDF file)

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID

Abstract:

Background: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).

Methods: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalization and up to 9 months of convalescence following COVID-19, respiratory syncytial virus (RSV) or influenza A (flu). Progressive fibrosing interstitial lung disease (PFILD) patients were included a positive control for severe, ongoing lung injury.

Results: Monocyte alterations in acute COVID-19 patients included aberrant expression of leucocyte migration molecules, continuing into convalescence (n=142) and corresponding to specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of chemokine receptor CXCR6 (p<0.0001) and adhesion molecule PSGL-1 (p<0.01), alongside preferential migration of monocytes towards CXCR6 ligand CXCL16 (p<0.05) which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in PFILD patients (p<0.001) confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited sustained reduction of the prostaglandin-generating enzyme COX-2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in RSV or flu convalescence.

Conclusions: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Source: Scott NA, Pearmain L, Knight SB, Brand O, Morgan DJ, Jagger C, Harbach S, Khan S, Shuwa HA, Franklin M, Kästele V, Williams T, Prise I, McClure FA, Hackney P, Smith L, Menon M, Konkel JE, Lawless C, Wilson J, Mathioudakis AG, Stanel SC, Ustianowski A, Lindergard G, Brij S, Diar Bakerly N, Dark P, Brightling C, Rivera-Ortega P, Lord GM, Horsley A; CIRCO; Piper Hanley K, Felton T, Simpson A, Grainger JR, Hussell T, Mann ER. Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID. Eur Respir J. 2023 Mar 15:2202226. doi: 10.1183/13993003.02226-2022. Epub ahead of print. PMID: 36922030. https://erj.ersjournals.com/content/early/2023/02/23/13993003.02226-2022 (Full article available as PDF file)

Demographic And Clinical Factors Associated With Long COVID

Risk factors for postacute sequelae of SARS-CoV-2 infection (“long COVID”) in community-dwelling populations remain poorly understood. Large-scale data, follow-up, comparison groups, and a consensus definition of long COVID are often lacking. Using data from the OptumLabs Data Warehouse on a nationwide sample of commercial and Medicare Advantage enrollees from the period January 2019 through March 2022, we examined demographic and clinical factors associated with long COVID, using two definitions of people who suffer symptoms long after they were first diagnosed with COVID-19 (“long haulers”).

We identified 8,329 long haulers using the narrow definition (diagnosis code), 207,537 long haulers using the broad definition (symptom based), and 600,161 non–long haulers (comparison group).

On average, long haulers were older and more likely female, with more comorbidities. Among narrow-definition long haulers, the leading risk factors for long COVID included hypertension, chronic lung disease, obesity, diabetes, and depression. Their time between initial COVID-19 diagnosis and diagnosis of long COVID averaged 250 days, with racial and ethnic differences. Broad-definition long haulers exhibited similar risk factors. Distinguishing long COVID from the progression of underlying conditions can be challenging, but further study may advance the evidence base related to the identification, causes, and consequences of long COVID.

Source: Song Z, Giuriato M. Demographic And Clinical Factors Associated With Long COVID. Health Aff (Millwood). 2023 Mar;42(3):433-442. doi: 10.1377/hlthaff.2022.00991. PMID: 36877912. https://pubmed.ncbi.nlm.nih.gov/36877912/

Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Long COVID describes a condition with symptoms that linger for months to years following acute COVID-19. Many of these Long COVID symptoms are like those experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: We wanted to determine if people with Long COVID experienced post-exertional malaise (PEM), the hallmark symptom of ME/CFS, and if so, how it compared to PEM experienced by patients with ME/CFS.

Methods: A questionnaire that asked about the domains of PEM including triggers, experience, recovery, and prevention was administered to 80 people seeking care for Long COVID at Bateman Horne Center. Their responses were compared to responses about PEM given by 151 patients with ME/CFS using chi-square tests of independence.

Results: All but one Long COVID respondent reported having PEM. There were many significant differences in the types of PEM triggers, symptoms experienced during PEM, and ways to recover and prevent PEM between Long COVID and ME/CFS. Similarities between Long COVID and ME/CFS included low and medium physical and cognitive exertion to trigger PEM, symptoms of fatigue, pain, immune reaction, neurologic, orthostatic intolerance, and gastrointestinal symptoms during PEM, rest to recover from PEM, and pacing to prevent PEM.

Conclusion: People with Long COVID experience PEM. There were significant differences in PEM experienced by people with Long COVID compared to patients with ME/CFS. This may be due to the newness of Long COVID, not knowing what exertional intolerance is or how to manage it.

Source: Vernon SD, Hartle M, Sullivan K, Bell J, Abbaszadeh S, Unutmaz D, Bateman L. Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Work. 2023 Mar 7. doi: 10.3233/WOR-220581. Epub ahead of print. PMID: 36911963. https://content.iospress.com/articles/work/wor220581 (Full text)

Predictors of impaired functioning among long COVID patients

Abstract:

Background: There is limited information on what acute factors predict more long-term symptoms from COVID-19.

Objective: Our objective was to conduct an exploratory factor analysis of self-reported symptoms at two time points of Long COVID-19.

Methods: Data from patients with Long COVID-19 were collected at the initial two weeks of contracting SARS CoV-2 and the most recent two weeks, with a mean duration of 21.7 weeks between the two-time points. At time point 2, participants also complete the Coronavirus Impact Scale (CIS), measuring how the COVID-19 pandemic affected various dimensions of their lives (e.g., routine, access to medical care, social/family support, etc.).

Results: At time 1, a three-factor model emerged consisting of Cognitive Dysfunction, Autonomic Dysfunction and Gastrointestinal Dysfunction. The analysis of time 2 resulted in a three-factor model consisting of cognitive dysfunction, autonomic dysfunction, and post-exertional malaise. Using factor scores from time 1, the Autonomic Dysfunction and the Gastrointestinal Dysfunction factor scores significantly predicted the CIS summary score at time two. In addition, the same two factor scores at time 1 predicted the occurrence of myalgic encephalomyelitis/chronic fatigue syndrome at time 2.

Conclusion: As Cognitive and Autonomic Dysfunction emerged as factors for both time points, suggesting health care workers might want to pay particular attention to these factors that might be related to later symptoms and difficulties with returning to pre-illness family life and work functioning.

Source: Jason LA, Dorri JA. Predictors of impaired functioning among long COVID patients. Work. 2023 Mar 8. doi: 10.3233/WOR-220428. Epub ahead of print. PMID: 36911958. https://content.iospress.com/articles/work/wor220428 (Full text)

My experience with ME/CFS and implications: A personal narrative

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating health condition characterized by overwhelming fatigue and post-exertional malaise, or exacerbation of symptoms following physical, mental, or emotional exertion. ME/CFS often impacts every aspect of an individual’s life, and one’s new reality may be much different from the daily life experienced before the onset of the condition. Though the long-term effects of COVID-19 have brought increased attention to chronic fatigue and related disorders, ME/CFS is still vastly understudied and frequently misunderstood.

People with ME/CFS are often passed between various healthcare providers as evidence-based treatments remain scarce. These patients are sometimes sent to rehabilitation professionals, who often lack appropriate education and experience with this patient population. This article describes the experience of a young woman and physical therapist with ME/CFS following COVID-19 infection, as well as potential implications for rehabilitation professionals and those who care for those with this condition.

Source: Sirotiak Z. My experience with ME/CFS and implications: A personal narrative. Work. 2023 Mar 9. doi: 10.3233/WOR-220487. Epub ahead of print. PMID: 36911961. https://content.iospress.com/articles/work/wor220487 (Full text)

Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review

Abstract:

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.

Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, Cochrane Library, medRxiv and bioRxiv up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.

Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36% ([95% CI 15.27-32.53]). The generalized symptom (19.57%, [95% CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76%, [95% CI 7.22-24.27]), neurologic (13.51%, [95% CI 6.52-22.40]), and psychiatric (12.30%, [95% CI 5.38-21.37]). Dyspnoea (22.75%, [95% CI 9.38-39.54]), fatigue (20.22%, [95% CI 9.19-34.09]), and headache (15.88%, [95% CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and >12 months were 26.41% ([95% CI 14.33-40.59]), 20.64% ([95% CI 17.06-24.46]), and 14.89% ([95% CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.

Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Source: Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, Chen X, Zhang AY, Kondratiuk AL, Shi PP, Zhang F, Sun J, Yue JL, Lin X, Shi L, Lalvani A, Shi J, Bao YP, Lu L. Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review. J Infect Public Health. 2023 Mar 7. doi: 10.1016/j.jiph.2023.03.005. Epub ahead of print. PMCID: PMC9990879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990879/ (Full text)