Tag: long covid symptoms

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.

Read the rest of this article HERE.

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

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.

Read the rest of this article HERE.

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)

Long COVID Patient Fact Sheet

‘Long COVID’ is the term that is often used to describe these persistent symptoms. You are considered to have ‘Long COVID’ when you are still having symptoms at least 4 weeks after the initial infection. Long COVID may also be referred to by other names such as post-COVID conditions, PASC (post-acute sequelae of COVID-19) or long-haul COVID.

Who Could Develop Long COVID?

Researchers around the world are trying to understand why some people develop Long COVID. People of all ages have been diagnosed with long COVID, including people with no underlying health conditions. Young and otherwise healthy people, and even those with mild infections, can be affected. More research is needed on the wide range of symptoms and why some people have more severe symptoms than others.

Read the full fact sheet as a PDF file HERE.

Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis

Abstract

Importance: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.

Data sources: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.

Study selection: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.

Data extraction and synthesis: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.

Main outcome(s) and measure(s): The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.

Results: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.

Conclusions and relevance: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Source: Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, Suen J, Robba C, Fraser J, Cho SM. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022 Jan 29;434:120162. doi: 10.1016/j.jns.2022.120162. Epub ahead of print. PMID: 35121209; PMCID: PMC8798975. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798975/ (Full text)

Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study

Abstract:

Background: Gastrointestinal infections represent a risk factor for functional gastrointestinal and somatoform extraintestinal disorders. We investigated the prevalence and relative risk (RR) of gastrointestinal and somatoform symptoms 5 months after SARS-CoV-2 infection compared with a control cohort.

Methods: One hundred and sixty-four SARS-CoV-2 infected patients and 183 controls responded to an online questionnaire about symptoms and signs during the acute phase of the infection and after 4.8 ± 0.3 months. Presence and severity of gastrointestinal symptoms, somatization, anxiety, and depression were recorded with standardized questionnaires. Stool form and presence of irritable bowel syndrome (IBS) were also recorded. Any association between exposure to infection and symptoms was evaluated by calculating crude and adjusted RR values and score differences with 95% confidence intervals (CI).

Key results: Fever, dyspnea, loss of smell/taste/weight, diarrhea, myalgia, arthralgia, and asthenia were reported by more than 40% of patients during the acute phase. Compared with controls, adjusted RRs for loose stools, chronic fatigue, and somatization were increased after infection: 1.88 (95% CI 0.99-3.54), 2.24 (95% CI 1.48-3.37), and 3.62 (95% CI 1.01-6.23), respectively. Gastrointestinal sequelae were greater in patients with diarrhea during the acute phase.

Conclusions & inferences: Mild gastroenterological symptoms persist 5 months after SARS-CoV-2 infection, in particular in patients reporting diarrhea in the acute phase. Infected patients are at increased risk of chronic fatigue and somatoform disorders, thus supporting the hypothesis that both functional gastrointestinal and somatoform disorders may have a common biological origin.

Source: Noviello D, Costantino A, Muscatello A, Bandera A, Consonni D, Vecchi M, Basilisco G. Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study. Neurogastroenterol Motil. 2022 Feb;34(2):e14187. doi: 10.1111/nmo.14187. Epub 2021 Jun 1. PMID: 34060710; PMCID: PMC8209890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209890/ (Full text)

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

Abstract:

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Source: Santinelli L, Laghi L, Innocenti GP, Pinacchio C, Vassalini P, Celani L, Lazzaro A, Borrazzo C, Marazzato M, Tarsitani L, Koukopoulos AE, Mastroianni CM, d’Ettorre G, Ceccarelli G. Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients. Front Nutr. 2022 Jan 12;8:756177. doi: 10.3389/fnut.2021.756177. PMID: 35096923; PMCID: PMC8790565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790565/ (Full text)

The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID

Abstract:

Background: Long-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments.

Methods: Eleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data.

Results: NHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26).

Conclusion: There are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection.

Summary statement: Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal.

Source:  James T. Grist, Guilhem J. Collier, Huw Walters, Mitchell Chen, Gabriele Abu Eid, Aviana Laws, Violet Matthews, Kenneth Jacob, Susan Cross, Alexandra Eves, Marianne Durant, Anthony Mcintyre, Roger Thompson, Rolf F. Schulte, Betty Raman, Peter A. Robbins, Jim M. Wild, Emily Fraser, Fergus Gleeson. The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID.
medRxiv 2022.02.01.22269999; doi: https://doi.org/10.1101/2022.02.01.22269999

Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort

Abstract:

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Source: Strahm C, Seneghini M, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, Meier Kleeb D, Möller JC, Rieder P, Ruetti M, Rutz R, Schmid HR, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Schmid D, Vernazza P, Kahlert CR, Kohler P. Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort. Clin Infect Dis. 2022 Jan 28:ciac054. doi: 10.1093/cid/ciac054. Epub ahead of print. PMID: 35090015. https://pubmed.ncbi.nlm.nih.gov/35090015/  (Full text available as PDF file)