Category: Overlapping Illnesses

Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study

Abstract:

Background: Many adolescents have been affected by the COVID-19 pandemic either directly by being infected with the virus or indirectly by lockdowns and restrictions influencing normal living. We aimed to investigate health, including symptoms of long COVID, in adolescents (aged 15-18 years) who tested positive for SARS-CoV-2 compared with a control group.

Methods: LongCOVIDKidsDK was a national, cross-sectional study carried out in Denmark, which included SARS-CoV-2-positive adolescents and matched controls. All Danish adolescents aged 15-18 years with a positive SARS-CoV-2 test during the period Jan 1, 2020, to July 12, 2021, and a control group matched (1:4) by age and sex were sent a survey from July 20, 2021. Participants had until Sept 15, 2021, to respond. Symptoms associated with COVID-19, school attendance, and health-related quality of life were investigated using ancillary questions and validated questionnaires (Paediatric Quality of Life Inventory [PedsQL] and Children’s Somatic Symptoms Inventory-24 [CSSI-24]). Statistical analyses included descriptive statistics and logistic regression. This study is registered at ClinicalTrials.gov, NCT04786353.

Findings: 24 315 adolescents with a positive SARS-CoV-2 test (case group) and 97 257 matched controls were invited to participate. 3013 matched controls were excluded because of suspected SARS-CoV-2 infection. 6630 (27·3%) responded in the case group and 21 640 (22·3%) responded and were eligible to participate in the control group. Across both groups, median age was 17·6 years (IQR 16·4-18·5), 16 277 (57·6%) of 28 270 responders were female, and 11 993 (42·4%) were male. Participants in the case group had greater odds of having at least one long COVID symptom lasting at least 2 months compared with the control group (3159 [61·9%] vs 12 340 [57·0%], odds ratio 1·22 [95% CI 1·15-1·30]; p<0·0001). Participants in the case group reported significantly lower symptom scores (ie, less somatic distress) on the CSSI-24 than in the control group: mean 10·7 (SD 11·4, median 7·0 [IQR 2·0-15·0]) versus 11·9 (10·6, 9·0 [4·0-17·0]; p<0·0001). Participants in the case group had better quality of life scores on the PedsQL than in the control group: physical functioning mean score 88·7 (SD 13·9, median 93·8 [IQR 84·4-100·0]) versus 86·5 (14·3, 90·6 [81·3-96·9]; p<0·0001); emotional functioning 77·1 (20·3, 80·0 [65·0-95·0]) versus 71·7 (21·4, 75·0 [60·0-90·0]; p<0·0001); social functioning 93·1 (12·5, 100·0 [90·0-100·0]) versus 88·4 (16·2, 95·0 [80·0-100·0]; p<0·0001); and school functioning 66·9 (22·5, 65·0 [60·0-85·0]) versus 62·9 (22·1, 65·0 [50·0-80·0]; p<0·0001). More participants in the case group than in the control group reported 16 or more sick days (1205 [18·2%] vs 2518 [11·6%]; p<0·0001) and 16 or more days of school absence (695 [10·5%] vs 1777 [8·2%]; p<0·0001).

Interpretation: Participants with SARS-CoV-2-positive tests had more long-lasting symptoms and sick leave, whereas participants in the control group had more short-lasting symptoms and worse quality of life. Knowledge of long COVID in adolescents is important to guide clinical recognition and management of this condition.

Funding: AP Møller and Chastine McKinney Møller Foundation.

Source: Kikkenborg Berg S, Dam Nielsen S, Nygaard U, Bundgaard H, Palm P, Rotvig C, Vinggaard Christensen A. Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc Health. 2022 Feb 7:S2352-4642(22)00004-9. doi: 10.1016/S2352-4642(22)00004-9. Epub ahead of print. PMID: 35143771; PMCID: PMC8820960.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820960/  (Full text)

Long covid: “Holistic” approach is best, given range of symptoms, say researchers

New research on long covid in adults and children supports the multidisciplinary approach to clinical care that is being provided at long covid clinics in England, experts have said.

“Long covid seems to be a condition where multiple symptoms are very common,” said Terence Stephenson, Nuffield professor of child health at the UCL Great Ormond Street Institute of Child Health in London, told a Science Media Centre briefing.

“I think the services that have been set up in England for young people do address that. They are holistic and comprehensive in their approach, rather than addressing single organs or single problems,” said Stephenson, who is the lead author of the Children and Young People with Long Covid (Clock) study, published in Lancet Adolescent and Child Health.1 “If you have a mixture of symptoms of headache, cough, and dizziness, you probably want to go to a service that can deal with you holistically with all your symptoms,” he added.

There are currently around 80 long covid clinics in England that take referrals from primary care for adults or children who are experiencing a range of symptoms that might include brain fog, anxiety, depression, breathlessness, and fatigue.

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Source: Iacobucci G. Long covid: “Holistic” approach is best, given range of symptoms, say researchers. BMJ. 2022 Feb 8;376:o336. doi: 10.1136/bmj.o336. PMID: 35135781. https://www.bmj.com/content/376/bmj.o336.long (Full text)

Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19

Abstract:

Objective: A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.

Methods: Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.

Results: This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%-40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.

Conclusions: The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.

Source: Krishnan K, Miller AK, Reiter K, Bonner-Jackson A. Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19. Arch Clin Neuropsychol. 2022 Feb 5:acac004. doi: 10.1093/arclin/acac004. Epub ahead of print. PMID: 35136912. https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acac004/6522998 (Full text)

Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID: Postexertional Symptom Exacerbation is an Abnormal Response to Exercise/Activity

Prolonged symptoms after infection with the novel coronavirus 2019 (SARS-COV-2) are an emerging challenge to individual patients, society, and clinicians. In a previous post on the JOSPT Blog, we identified several lessons from research and clinical practice in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that are important lessons for long COVID. The purpose of this post is to discuss the phenomenon of postexertional symptom exacerbation (PESE) and its clinical identification to recognize the potential onset of long COVID.

Data from a large international web-based patient survey indicate substantial symptom overlap between postacute SARS-COV-2 infection (long COVID) and ME/CFS at 6 months following the onset of first symptoms. Three quarters of respondents noted disabling fatigue and over half noted cognitive dysfunction.4 A unique finding of this survey was that 75% of respondents noted PESE, which is a worsening of symptoms after activity/exercise.4 PESE is foundational to the diagnosis of ME/CFS and it is common with long COVID.4,5 This observation suggests we can further extend lessons from ME/CFS to develop our understanding of long COVID.

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Source: Todd E. Davenport Staci R. Stevens Jared Stevens Christopher R. Snell J. Mark Van Ness. Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID: Postexertional Symptom Exacerbation is an Abnormal Response to Exercise/Activity. Published online on February 2, 2022 https://doi.org/10.2519/jospt.blog.20220202

Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects

Abstract:

Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells.
Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.
Source: Russo A, Tellone E, Barreca D, Ficarra S, Laganà G. Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects. International Journal of Molecular Sciences. 2022; 23(4):2171. https://doi.org/10.3390/ijms23042171 https://www.mdpi.com/1422-0067/23/4/2171/htm (Full text)

FEATURE: Reduced brain function, immune disorder a possibility of “long COVID”

What happens to the body of a person who suffers from the long-term effects of the novel coronavirus?

A 33-year-old reporter for Kyodo News, my ailments related to COVID-19 continue to this day, more than a year after I recovered from the initial viral infection. Although I have seen slight improvements through treatment, I am still far from my former self.

In January, after an examination at the National Center of Neurology and Psychiatry in Tokyo, I was told I might be suffering from an immune disorder and reduced brain function due to the virus.

The exam I underwent included a brain perfusion scan, a test to determine blood flow in certain regions of the brain. It involves injecting radiotracers — radioactive substances that emit tiny particles — into a vein. A special camera is then used to track how the radioactive substance spreads throughout the brain to determine which areas are most active, which is believed to be indicated by blood supply.

Read the rest of this article HERE.

Source: Sayako Akita, Kyodo News, Feb 14, 2022. https://english.kyodonews.net/news/2022/02/263518f1cd8b-feature-reduced-brain-function-immune-disorder-a-possibility-of-long-covid.html

Study points to vagus nerve dysfunction as a central pathophysiological feature of long COVID

New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April) suggests that many of the symptoms connected to post-COVID syndrome (PCC, also known as long COVID) could be linked to the effect of the virus on the vagus nerve – one of the most important multi-functional nerves in the body. The study is by Dr Gemma Lladós and Dr Lourdes Mateu, University Hospital Germans Trias i Pujol, Badalona, Spain, and colleagues.

The vagus nerve extends from the brain down into the torso and into the heart, lungs and intestines, as well as several muscles including those involved in swallowing. As such, this nerve is responsible for a wide variety of bodily functions including controlling heart rate, speech, the gag reflex, transferring food from the mouth to the stomach, moving food through the intestines, sweating, and many others.

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Source: European Society of Clinical Microbiology and Infectious Diseases. https://www.news-medical.net/news/20220212/Study-points-to-vagus-nerve-dysfunction-as-a-central-pathophysiological-feature-of-long-COVID.aspx

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

Abstract:

Objective: To describe the clinical data from the first 108 patients seen in the Mayo Clinic post-COVID-19 care clinic (PCOCC).

Methods: After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review.

Results: Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively.

Conclusion: In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.

Source: Ganesh R, Grach SL, Ghosh AK, Bierle DM, Salonen BR, Collins NM, Joshi AY, Boeder ND Jr, Anstine CV, Mueller MR, Wight EC, Croghan IT, Badley AD, Carter RE, Hurt RT. The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome. Mayo Clin Proc. 2022 Feb 5:S0025-6196(21)00888-0. doi: 10.1016/j.mayocp.2021.11.033. Epub ahead of print. PMID: 35135695; PMCID: PMC8817110. https://www.sciencedirect.com/science/article/pii/S0025619621008880 (Full text)

Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research

As the COVID-19 pandemic continues to affect hundreds of millions of people worldwide, autonomic complications are being recognized with increasing frequency in both the acute and chronic form of the illness, the latter now designated as post-acute sequelae of SARS-CoV-2 (PASC), colloquially termed long-COVID. Tachycardia is a common symptom of PASC, and some patients may be diagnosed with postural tachycardia syndrome (POTS) or inappropriate sinus tachycardia (IST). While post-COVID POTS has garnered more attention from the scientific and popular press, IST may be equally or more common and has been reported in survivors of the prior SARS coronavirus pandemic [1]. The etiology of IST is unknown; however, the proposed mechanisms overlap with those of POTS, including increased sympathetic and/or reduced cardiovagal activity.

In their recent publication [2], “Inappropriate sinus tachycardia in post-COVID-19 syndrome” Aranyo and colleagues identified 200 consecutive patients with PASC. IST was defined according to consensus criteria as symptomatic sinus rhythm rate ≥ 100 bpm at rest with a mean 24-h heart rate above 90 beats/min in the absence of any acute physiological demand or conditions known to produce sinus tachycardia. All patients underwent a 10-min active stand test to help rule out disorders of orthostatic intolerance, such as POTS and orthostatic hypotension. In addition, patients underwent an echocardiogram, 24-h Holter monitoring, a 6-min walk test (6MWT), and measurements of blood markers of inflammation and myocardial damage, including ferritin and interleukin-6. Heart rate variability (HRV) analysis was performed from the 24-h Holter data, focusing on standard time-domain parameters such as the RR interval, standard deviation of the inter-beat interval (SDNN), and the percentage of adjacent NN intervals that differed from each other by more than 50 ms (PNN50), as well as standard frequency-domain parameters including very low-frequency (VLF; 0.003–0.04 Hz), low-frequency (LF; 0.04–0.15 Hz), and high-frequency (HF; 0.15–0.40 Hz) bands. The HF band and PNN50 are regarded as indicators of the parasympathetic influence on heart rate, whereas the LF and VLF bands have more complex physiology that integrates both the sympathetic and parasympathetic components. Comparison groups included age- and gender-matched PCR-confirmed COVID patients without IST (fully recovered group, N = 19) and age- and gender-matched controls who had no history of SARS-COV-2 disease, as confirmed by negative serology (uninfected group, N = 17).

The authors identified 40 patients with IST from the cohort of 200 patients with PASC yielding an estimated prevalence of 20%. Eighty-five percent of the subjects were women and 83% had a history of mild COVID defined as the presence of symptoms without evidence of viral pneumonia or hypoxia. Most patients reported cardiopulmonary symptoms at the onset of their infection, including palpitations (90%), dyspnea (83%), and chest pain (78%); 53% reported dizziness and 48% anosmia. Compared to fully recovered patients, patients with IST were more likely to report palpitations (90% vs. 5%; p < 0.001), dyspnea (82% vs. 16%; p < 0.001), chest pain (78% vs. 21%; p < 0.001), headache (73% vs. 37%; p = 0.007), dizziness (53% vs. 5%; p = 0.002), diarrhea (53% vs. 16%; p = 0.003), and dermatological alterations (35% vs. 5%; p = 0.009) during the acute phase of SARS-CoV-2 infection. Patients with IST were also more likely to report environmental allergies compared to the fully recovered and uninfected groups (25% vs. 0%; p = 0.01), hinting at a potential mast cell component.

The 6MWT showed that patients with PASC with IST had a significantly reduced exercise capacity, with a 60% reduction in their estimated normal distance. Frequency analysis of heart rate variability revealed that patients with IST had a reduction in VLF, LF, and HF domains compared to controls, with more severe impairment in the parasympathetic-influenced domains. There was no difference in blood inflammatory markers between groups.

Limitations of this work include the small sample sizes of the control groups, as well as the lack of systematic pulmonary evaluations, measurement of markers of physical deconditioning, and systematic autonomic testing. Nonetheless, this study provides the first glimpse of how common IST may be in PASC and adds to the growing body of literature on autonomic dysfunction as a potential mechanism in PASC-related disability. With the Omicron variant currently surging across the globe, PASC-related autonomic complications will, unfortunately, be with us for some time, and clinicians should be familiar with their manifestations and potential treatment options.

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Source: Miglis MG, Larsen N, Muppidi S. Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research. Clin Auton Res. 2022 Feb 7. doi: 10.1007/s10286-022-00854-5. Epub ahead of print. PMID: 35129713. https://link.springer.com/article/10.1007/s10286-022-00854-5 (Full text)

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis

Abstract:

Background: Post-acute COVID-19 Syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.

Objectives: To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.

Data sources: Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.

Study eligibility criteria: Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed SARS-CoV-2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.

Methods: Random-effect meta-analysis was performed to produce pooled prevalence for each symptom at 4 different follow-up time intervals. Between-studies heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study level variables. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.

Results: After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257,348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder and concentration difficulty (32%, 25%, 24%, and 22% respectively at 3-<6 months follow-up), effort intolerance, fatigue, sleep disorder and dyspnea (45%, 36%, 29% and 25% respectively at 6-<9 months follow-up), fatigue (37%) and dyspnea (21%) at 9-<12 months and fatigue, dyspnea, sleep disorder, myalgia (41%, 31%, 30%, and 22% respectively at >12 months follow-up). There was substantial between-studies heterogeneity for all reported symptoms prevalence. Meta-regressions identified statistically significant effect modifiers: world region, male gender, diabetes mellitus, disease severity and overall study quality score. Five of six studies including a comparator group consisting of COVID-19 negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.

Conclusions: This systematic review found that a large proportion of patients experience PACS 3 to 12 months after recovery from the acute phase of COVD-19. However, available studies of PACS are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptoms definitions and measurements and longer follow-up.

Source: Alkodaymi MS, Omrani OA, Fawzy NA, Shaar BA, Almamlouk R, Riaz M, Obeidat M, Obeidat Y, Gerberi D, Taha RM, Kashour Z, Kashour T, Berbari EF, Alkattan K, Tleyjeh IM. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis. Clin Microbiol Infect. 2022 Feb 3:S1198-743X(22)00038-6. doi: 10.1016/j.cmi.2022.01.014. Epub ahead of print. PMID: 35124265; PMCID: PMC8812092. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812092/ (Full text)