Category: Overlapping Illnesses

SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis

Abstract:

Background: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as “long COVID”. Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC.

Methods: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses.

Results: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)).

Conclusions: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.

Source: Kelly JD, Curteis T, Rawal A, Murton M, Clark LJ, Jafry Z, Shah-Gupta R, Berry M, Espinueva A, Chen L, Abdelghany M, Sweeney DA, Quint JK. SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis. Eur Respir Rev. 2023 Jul 12;32(169):220254. doi: 10.1183/16000617.0254-2022. PMID: 37437914; PMCID: PMC10336551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336551/ (Full text)

People with Long Covid and ME/CFS Exhibit Similarly Impaired Balance and Physical Capacity: A Case-Case-Control Study

Abstract:

Purpose: Postural sway and physical capacity had not previously been compared between people with long COVID and people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Therefore, this study determined postural sway and physical capacity in people with long COVID (∼16 month illness duration; n=21) and ME/CFS (∼16 year illness duration; n=20), versus age-matched healthy controls (n=20).

Methods: Postural sway was during a 30 s static stand test. Physical capacity was determined using the timed up and go test and five times sit to stand test. Throughout, participants wore isoinertial measurement units.

Results: Postural sway was worse (i.e. greater) in people with long COVID and ME/CFS than controls, but not different between long COVID and ME/CFS. Performance of the timed up and go test and five times sit to stand test were worse in long COVID and ME/CFS than controls, but not different between long COVID and ME/CFS. 87% and 13% of long COVID and ME/CFS participants exceeded the threshold for muscle weakness in the five times sit to stand test and timed up and go test, respectively.

Conclusions: These data suggest that both people with long COVID and people with ME/CFS have similarly impaired balance and physical capacity. Therefore, there is an urgent need for interventions to target postural sway and physical capacity in people with ME/CFS, and given the current pandemic, people with long COVID.

Source: Lawrence D. Hayes, PhD, Nilihan E.M. Sanal-Hayes, PhD, Marie Mclaughlin, PhD, Ethan C.J. Berry, BSc (Hons), Nicholas F. Sculthorpe, PhD. People with Long Covid and ME/CFS Exhibit Similarly Impaired Balance and Physical Capacity: A Case-Case-Control Study. The American Journal of Medicine. Published: July 23, 2023 DOI: https://doi.org/10.1016/j.amjmed.2023.06.028 https://www.amjmed.com/article/S0002-9343(23)00465-5/fulltext#%20

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part II

Abstract:

Background: There has been some effort to map the prevalence, frequency, and severity of symptoms of long-COVID at local and national levels. However, what is frequently absent from such accounts is details of the impact the disease and its symptoms have had on those living with the condition. In this manuscript, we present details of impact to work, caring, and mental health gathered using a cross-sectional survey.

Methods: Data were collected using an online survey which was available from 21st April 2022 to 5th August 2022. Included participants had either self-diagnosed or confirmed long-COVID, were living in Scotland, and were ≥18 years old. Hospitalisation during initial COVID-19 infection was an exclusion criterion. Participants were asked to report on the impact of their illness on everyday activities such as working, studying, or caring. They also completed an assessment of their current mood.

Results: People with long-COVID were often severely impacted in their ability to work and study. Severe impact on work and study were predicted by more severe and more frequent fatigue, more severe pain, and more severe cognitive impairment. Respondents’ ability to care for child dependants was also associated with more severe and more frequent fatigue, as well as more severe cognitive impairments. More severe pain associated with greater impact on adult care. Negative mood correlated most strongly with frequency and severity of neurological symptoms, including lack of attention, loss of smell, impaired sense of smell, loss of taste, impaired sense of taste, and loss of appetite.

Conclusions: Long-COVID has a significant impact on ability to work, study, and care for dependants. The severity of this impact is associated with specific symptom burden, including fatigue, pain, and cognitive impairment.

Source: Mclaughlin M, Cerexhe L, Macdonald E, Ingram J, Sanal-Hayes NEM, Hayes LD, Meach R, Carless D, Sculthorpe N. A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part II. Am J Med. 2023 Jul 19:S0002-9343(23)00461-8. doi: 10.1016/j.amjmed.2023.07.009. Epub ahead of print. PMID: 37478960. https://www.amjmed.com/article/S0002-9343(23)00461-8/fulltext (Full text)

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part I

Abstract:

Background: Commonly reported symptoms of long-COVID may have different patterns of prevalence and presentation across different countries. While some limited data has been reported for the UK, national specificity for Scotland is less clear. We present a cross-sectional survey to examine the symptom prevalence, frequency and severity of long-COVID for people living with the condition in Scotland.

Methods: An online survey was created in the English language and was available between 21st April 2022 and 5th August 2022. Participants were included if they were ≥18 years old, living in Scotland, and had self-diagnosed or confirmed Long-COVID; and excluded if they were hospitalised during their initial infection. Within this article we quantify symptom prevalence, frequency, severity, and duration.

Results: Participants (n=253) reported the most prevalent long-COVID symptoms to be post-exertional malaise (95%), fatigue/tiredness (85%), and cognitive impairment (68%). Fatigue/tiredness, problems with activities of daily living (ADL), and general pain were most frequently occurring, whilst sleep difficulties, problems with ADL, and nausea were the most severe. Scottish Index of Multiple Deprivation associated with symptom number, severity and frequency, while vaccine status, age, sex, and smoking status had limited or no association.

Conclusions: These findings outline the challenges faced for those living with long COVID and highlight the need for longitudinal research to ascertain a better understanding of the condition and its longer-term societal impact.

Source: Mclaughlin M, Cerexhe L, Macdonald E, Ingram J, Sanal-Hayes NEM, Hayes LD, Meach R, Carless D, Sculthorpe N. A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part I. Am J Med. 2023 Jul 20:S0002-9343(23)00460-6. doi: 10.1016/j.amjmed.2023.07.004. Epub ahead of print. PMID: 37481021. https://www.amjmed.com/article/S0002-9343(23)00460-6/fulltext (Full text)

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment

Abstract:

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.

To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment.

Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected).

Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNg, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.

We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

Source: Bianca Besteher, Tonia Rocktaeschel, Alejandra Patricia Garza, Marlene Machnik, Johanna Ballez, Dario Lucas Helbing, Katrhin Finke, Philipp Reuken, Daniel Guellmar, Christian Gaser, Martin Walter, Nils Opel, Ildiko Rita Dunay. Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment. medRxiv 2023.07.21.23292988; doi: https://doi.org/10.1101/2023.07.21.23292988 https://www.medrxiv.org/content/10.1101/2023.07.21.23292988v1v (Full text available as PDF file)

Long COVID as a never-ending puzzle: the experience of primary care physicians

Abstract:

Background: Long COVID provides a new context in which primary healthcare needs to be reexamined, especially because it has health and social dimensions. The experiences of care for patients with long COVID and primary care physicians’ perceptions are an unexplored area.

Aim: To explore the experiences of Slovenian primary care physicians in management and treatment of patients with long COVID.

Design & setting: A qualitative interview study in Slovenian primary care was carried out between November 2021 and April 2022.

Method: Semi-structured interviews were held with physicians that had treated patients with long COVID until saturation was reached. Qualitative content analysis (QCA) was used to analyze the data collected.

Results: Seventeen participants were interviewed. Six categories were defined based on the coding process: the definition and symptoms of long COVID; social exclusion, sick leave, returning to the work environment, cooperation with rehabilitation centers and the importance of trust and good communication with the patient.

Conclusion: The study shows the experiences of Slovenian primary care physicians in the management and treatment of long COVID. The problems related to long COVID were divided into two groups: health problems and psycho-social problems. Slovenian physicians have the greatest problems with dealing with the patient’s ability to work. It was found that adequate communication and trust between physicians and patients are two important indicators for an integrated model of managing long COVID.

Source: Rotar Pavlic D, Maksuti A, Mihevc M, Munda A, Medija K, Strauch V. Long COVID as a never-ending puzzle: the experience of primary care physicians. BJGP Open. 2023 Jul 12:BJGPO.2023.0074. doi: 10.3399/BJGPO.2023.0074. Epub ahead of print. PMID: 37437953. https://bjgpopen.org/content/early/2023/07/11/BJGPO.2023.0074 (Full text available as PDF file)

Post COVID-19 symptoms are common, also among young adults in the general population

Abstract:

Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the prevalence and symptoms of post COVID-19 and its potential risk factors in young adults.

Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26).

The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms.

Source: Mogensen I, Ekström S, Hallberg J, Georgelis A, Melén E, Bergström A, Kull I. Post COVID-19 symptoms are common, also among young adults in the general population. Sci Rep. 2023 Jul 12;13(1):11300. doi: 10.1038/s41598-023-38315-2. PMID: 37438424; PMCID: PMC10338459. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338459/ (Full text)

Hypothesis: Matrix metalloproteinase inhibition with low-dose doxycycline in Long COVID and ME/CFS

Abstract:

Nonselective matrix metalloproteinase (MMP) inhibition with FDA approved subantimicrobial dose doxycycline formulations could improve systemic symptoms in at least a subset of patients with Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared to those who receive placebo.

Source: Sanders, E.C. (2023). Hypothesis: Matrix metalloproteinase inhibition with low-dose doxycycline in Long COVID and ME/CFS. Patient-Generated Hypotheses Journal for Long COVID & Associated Conditions, Vol. 1, 21-29 https://patientresearchcovid19.com/hypothesis-matrix-metalloproteinase-inhibition-with-low-dose-doxycycline-in-long-covid-and-me-cfs-pghj-issue1-may2023/ (Full text)

Hypothesis: Symptomatic myodesopsia/vitreous floaters may constitute a risk factor for Long COVID and ME/CFS

Abstract:

The ophthalmological condition known as myodesopsia or vitreous floaters results from aggregates of proteins or cellular debris in the vitreous body casting shadows onto the retina that are perceived as objects moving through the visual field. While this is commonly viewed as a benign condition associated with aging, a growing body of research suggests that for some patients it can severely impact visual function and quality of life. Myodesopsia is often caused by posterior vitreous detachment, but can also result from other conditions such as asteroid hyalosis, uveitis, or myopic vitreopathy.

There are strong reasons to suspect that its presence may be indicative of a susceptibility to collagen degradation in response to inflammatory triggers, which may represent a risk factor for the development of Long COVID, ME/CFS, or related chronic illnesses. Evidence for such susceptibility includes the presence of collagen-degrading enzymes in the vitreous, associations with other connective tissue disorders, and links between myodesopsia and infections with various pathogens.

Source: Mazewski, M. (2023). Hypothesis: Symptomatic myodesopsia/vitreous floaters may constitute a risk factor for Long COVID and ME/CFS. Patient-Generated Hypotheses Journal for Long COVID & Associated Conditions, Vol. 1, 13-20 https://patientresearchcovid19.com/hypothesis-symptomatic-myodesopsia-vitreous-floaters-may-constitute-a-risk-factor-for-long-covid-and-me-cfs-pghj-issue1-may2023/ (Full text)

Hypothesis: Astrocyte dysregulation of sympathetic nervous system causes metabolic dysfunction in subset of Long COVID and ME/CFS patients

Abstract:

An overactive sympathetic nervous system (SNS) may cause one subtype of Long COVID. People who are genetically at risk for noradrenergic nerve problems may develop an overactive SNS after an infection. Alternatively, genetic or virus-induced dysregulation of astrocytes could lead to overactivation of the SNS. An overactive SNS could disrupt regulation of immune cells, energy metabolism, sleep homeostasis, respiratory rate, gastrointestinal function, and systemic and cerebral blood pressure, causing fatigue and cognitive dysfunction.

Hypothesis: Long COVID refers to symptoms that continue for more than four weeks after onset of acute COVID-19 illness. This umbrella term includes a wide variety of symptoms and presentations. Long COVID patients may have different types of biological dysfunction, meaning that there may be distinct subtypes of Long COVID. One possible subtype is sympathetic nervous system (SNS) over-activation. This subtype may exist in both Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)1.

Underlying mechanisms of the SNS overactivation subtype: Theoretically, patients with this subtype already have a genetic dysregulation of neuronal norepinephrine (NE) release/clearance or noradrenergic receptor sensitivity2. This latent genetic dysfunction of NE signaling may not cause significant problems unless there is a trigger that causes excess NE release.

As NE affects immune cell signaling, this could result in an over-activation or prolonged activation of the immune system in response to infection with SARS-CoV-2, the virus that causes COVID-193 . This subtype could explain why ME/CFS is often triggered by a virus or brain injury, as these occurrences can trigger noradrenergic signaling3.

Possible mechanisms for the SNS overactivation subtype include viral reservoirs, antibody reaction, and dysregulation of noradrenergic receptor expression. In Long COVID patients, viral antigens and reservoirs that remain in the body long after the initial infection may keep the overactive immune system in an inflammatory state4,5. A healthy person may not react to these SARS-CoV-2 reservoirs, as their functional immune cells should develop immune tolerance. Another possibility is that the immune system is reacting to SARS-CoV-2 antibodies.

Finally, it is possible that excess extracellular NE could keep the SNS and noradrenergic systems in the brain stuck in an overactive state. A prolonged period of increased levels of extracellular NE could lead to dysregulation of noradrenergic receptor expression. The excess extracellular NE may be due to a prolonged release of excess NE during the initial infection, or a failure of the negative feedback mechanisms that should reduce NE release.

Symptoms of an overactive SNS: An overactive SNS explains many of the symptoms found in Long COVID patients, such as IBS/gastrointestinal symptoms6, heart palpitations7, and sleep disturbance8. Additionally, in orthostatic intolerance, which is common in Long COVID and ME/CFS, the release of NE causes pronounced tachycardia. This rapid heart rate may cause palpitations, breathlessness, and chest pain.

Dysfunctional energy metabolism causes fatigue and cognitive dysfunction: An important piece of the puzzle is to explain how a dysregulated SNS could lead to chronic fatigue and brain fog (cognitive dysfunction). The most likely explanation is a dysregulation of metabolic function. There are many ways excess NE could affect metabolism, including enhancing aerobic glycolysis and depleting glycogen stores.

Source: Carnac, T. (2023). Hypothesis: Astrocyte dysregulation of sympathetic nervous system causes metabolic dysfunction in subset of Long COVID and ME/CFS patients. Patient-Generated Hypotheses Journal for Long COVID & Associated Conditions, Vol. 1, 36-43 https://patientresearchcovid19.com/hypothesis-astrocyte-dysregulation-of-sympathetic-nervous-system-causes-metabolic-dysfunction-in-subset-of-long-covid-and-me-cfs-patients-pghj-issue1-may2023/ (Full text)