Tag: long covid symptoms

Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid

Abstract:

After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required.

We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells.

Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.

Source: Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L; NIHR BioResource; Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR. Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid. Sci Adv. 2024 Feb 23;10(8):eadi9379. doi: 10.1126/sciadv.adi9379. Epub 2024 Feb 21. PMID: 38381822; PMCID: PMC10881041. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881041/ (Full text)

Impact of sleep disruption on cognitive function in patients with postacute sequelae of SARS-CoV-2 infection: initial findings from a Neuro-COVID-19 clinic

Abstract:

Introduction: Fatigue, brain fog, and sleep disturbance are among the most common symptoms of postacute sequelae of SARS-CoV-2 infection (PASC). We sought to determine the impact of sleep disruption on cognition and quality of life in patients with neurologic manifestations of PASC (Neuro-PASC).
Methods: Thirty-nine patients were recruited from Neuro-COVID-19 clinic. Mean age was 48.1 years, 71.8% were female, and 82% were never hospitalized for COVID-19. Patients were evaluated via clinical assessment, quality-of-life measures in domains of cognitive function, fatigue, sleep disturbance, anxiety, and depression, NIH Toolbox cognitive tests, and 7 days of wrist actigraphy.
Results: The median number of neurologic symptoms attributed to PASC was 6, with brain fog being the most common in 89.7%. Regarding non-neurologic symptoms, 94.9% complained of fatigue and 74.4% of insomnia. Patients reported significant impairment in all quality-of-life domains and performed worse in a task of attention compared to a normative US population. Actigraphy showed Neuro-PASC patients had lower sleep efficiency, longer sleep latency (both p < 0.001), and later sleep midpoint (p = 0.039) compared to 71 age-matched healthy controls with no PASC history. Self-reported cognitive symptoms correlated with the severity of fatigue (p < 0.001), anxiety (p = 0.05), and depression (p < 0.01). Objective evidence of sleep disruption measured by wakefulness after sleep onset, sleep efficiency, and latency were associated with decreased performance in attention and processing speed.
Conclusion: Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep disruption on the cognitive function and quality of life of patients with PASC.

Source: Kathryn J Reid, Louis T Ingram, Millenia Jimenez, Zachary S Orban, Sabra M Abbott, Daniela Grimaldi, Kristen L Knutson, Phyllis C Zee, Igor J Koralnik, Mathew B Maas, Impact of sleep disruption on cognitive function in patients with postacute sequelae of SARS-CoV-2 infection: initial findings from a Neuro-COVID-19 clinic, SLEEP Advances, Volume 5, Issue 1, 2024, zpae002, https://doi.org/10.1093/sleepadvances/zpae002 https://academic.oup.com/sleepadvances/article/5/1/zpae002/7517273 (Full text)

Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions

Abstract:

Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients.

One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants’ smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%).

These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations.

Source: Rogn Å, Jensen JL, Iversen PO, Singh PB. Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions. Sci Rep. 2024 Feb 11;14(1):3455. doi: 10.1038/s41598-024-53919-y. PMID: 38342941; PMCID: PMC10859368. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10859368/ (Full text)

Cardiorespiratory abnormalities in ICU survivors of COVID-19 with Post-acute Sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation

Abstract:

Post-acute Sequelae of SARS-CoV-2 infection (PASC) often leads to exertional intolerance and reduced exercise capacity, particularly in individuals previously admitted to an intensive care unit (ICU). However, the impact of invasive mechanical ventilation (IMV) on PASC-associated cardiorespiratory abnormalities during exercise remains poorly understood.

This single-center, cross-sectional study aimed to gather knowledge on this topic. Fifty-two patients with PASC recruited ~6 months after ICU discharge were clustered based on their need for IMV (PASC+IMV, n=27) or non-invasive support therapy (PASC+NIS, n=25). Patients underwent pulmonary function and cardiopulmonary exercise testing (CPX), and were compared to a reference group (CONTROL, n=19) comprising individuals of both sexes with similar age, comorbidities, and physical activity levels, but without a history of COVID-19 illness.

Individuals with PASC, irrespective of support therapy, presented with higher rates of cardiorespiratory abnormalities than CONTROL, especially dysfunctional breathing patterns, dynamic hyperinflation, reduced oxygen uptake and oxygen pulse, and blunted heart rate recovery (all P<0.05). Only the rate of abnormal oxygen pulse was greater among PASC+IMV than PASC+NIS (P=0.05). Mean estimates for all CPX variables were comparable between PASC-IMV and PASC-NIS (all P>0.05).

These findings indicate significant involvement of both central and peripheral factors, leading to exertional intolerance in individuals with PASC previously admitted to the ICU, regardless of their need for IMV.

Source: Longobardi I, Prado DMLD, de Andrade DCO, Goessler KF, de Oliveira Júnior GN, Azevedo RA, Leitão AE, Santos JVP, de Sá Pinto AL, Gualano B, Roschel H. Cardiorespiratory abnormalities in ICU survivors of COVID-19 with Post-acute Sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation. Am J Physiol Heart Circ Physiol. 2024 Feb 9. doi: 10.1152/ajpheart.00073.2024. Epub ahead of print. PMID: 38334972. https://pubmed.ncbi.nlm.nih.gov/38334972/ (Full study available as PDF file)

Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year

Abstract:

Purpose: Long coronavirus disease (COVID) poses a significant health concern for a substantial proportion of COVID-19 patients. Viral pathogenesis studies suggest the potential of central nervous system (CNS) affection in the acute phase of COVID-19 predicting long COVID.

This study investigates whether acute COVID-19 symptoms, particularly headache and disturbed smell and taste, predict manifestations of long COVID.

Methods: This prospective cohort study included COVID-19 patients hospitalized between March 2020, and May 2021. One year after discharge, patients responded to a symptom questionnaire. Logistic regression analysis was used to determine the odds ratio (OR) for these outcomes.

Results: Of 288 eligible patients, 111 responded to the follow-up questionnaire. At 1 year follow-up, disturbed smell and taste during acute COVID-19 did not elevate the risk of long COVID. However, patients with acute headache demonstrated a tendency towards an elevated risk of CNS-related long COVID. Notably, this risk significantly increased in patients reporting dizziness (adjusted OR=4.20; 95% confidence interval (CI) 1.19 – 14.85). Neither disturbed smell and taste nor headache during acute COVID-19 indicated a statistically significant risk of worsening in fatigue, health, or total symptom score at 1-year follow-up.

Conclusion: Headache, and not disturbed smell and taste, predicted CNS-related long COVID. Further research is warranted to clarify pathways connecting CNS-related symptoms during acute COVID-19 with long COVID, aiding the efforts of addressing the range of symptoms observed among long COVID patients and developing effective interventions.

Source: Jane Agergaard. Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year, 07 February 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3930891/v1] https://www.researchsquare.com/article/rs-3930891/v1 (Full text)

Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study

Abstract:

Background: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort.

Methods: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found.

Results: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients.

Conclusions: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.

Source: Cornelissen MEB, Bloemsma LD, Vaes AW, Baalbaki N, Deng Q, Beijers RJHCG, Noij LCE, Houweling L, Bazdar S, Spruit MA, Maitland-van der Zee AH; on behalf of the P4O2 Consortium. Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study. J Transl Med. 2024 Feb 21;22(1):191. doi: 10.1186/s12967-024-04979-1. PMID: 38383493. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-04979-1 (Full text)

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

Abstract:

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog.

Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Source: Greene, C., Connolly, R., Brennan, D. et al. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nat Neurosci (2024). https://doi.org/10.1038/s41593-024-01576-9 https://www.nature.com/articles/s41593-024-01576-9 (Full text)

Cognitive and Mental Health Trajectories of COVID-19: Role of Hospitalisation and Long-COVID Symptoms

Abstract:

Background: There is considerable evidence of cognitive impairment post COVID-19, especially in individuals with long-COVID symptoms, but limited research objectively evaluating whether such impairment attenuates or resolves over time, especially in young and middle-aged adults.

Methods: Follow-up assessments (T2) of cognitive function (processing speed, attention, working memory, executive function, memory) and mental health were conducted in 138 adults (18-69 years) who had been assessed six months earlier (T1). Of these, 88 had a confirmed history of COVID-19 at T1 assessment (≥20 days post-diagnosis) and were also followed-up on COVID-19 related symptoms (acute and long-COVID); 50 adults had no known COVID-19 history at any point up to their T2 assessment.

Results: From T1 to T2, a trend-level improvement occurred in intra-individual variability in processing speed in the COVID, relative to the non-COVID group. However, longer response/task completion times persisted in participants with COVID-19 related hospitalisation relative to those without COVID-19 related hospitalisation and non-COVID controls. There was a significant reduction in long-COVID symptom load, which correlated with improved executive function in non-hospitalised COVID-19 participants. The COVID group continued to self-report poorer mental health, irrespective of hospitalisation history, relative to non-COVID group.

Conclusions: Although some cognitive improvement has occurred over a six-month period in young and middle-aged COVID-19 survivors, cognitive impairment persists in those with a history of COVID-19 related hospitalisation and/or long-COVID symptoms. Continuous follow-up assessments are required to determine whether cognitive function improves or possibly worsens, over time in hospitalised and long-COVID participants.

Source: Vakani K, Ratto M, Sandford-James A, Antonova E, Kumari V. Cognitive and Mental Health Trajectories of COVID-19: Role of Hospitalisation and Long-COVID Symptoms. Eur Psychiatry. 2024 Feb 5:1-40. doi: 10.1192/j.eurpsy.2024.7. Epub ahead of print. PMID: 38312039. https://www.researchgate.net/publication/377977040_Cognitive_and_Mental_Health_Trajectories_of_COVID-19_Role_of_Hospitalisation_and_Long-COVID_Symptoms (Full text)

Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study

Abstract:

Objective: To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome.

Design: A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022.

Setting: The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID.

Participants: Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred.

Intervention: During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life.

Primary and secondary outcome measures: Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms.

Results: In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients’ comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI: 1.01 to 1.04), COVID-19 severity (OR=0.42, 95% CI: 0.21 to 0.82), number of comorbidities (OR=1.22, 95% CI: 1.01 to 1.5), metabolic (OR=2.52, 95% CI: 1.25 to 5.27), pulmonary (OR=1.87, 95% CI: 1.10 to 3.32) and autoimmune diseases (OR=4.57, 95% CI: 1.57 to 19.41) increased the risk of the physical macro symptoms.

Conclusions: Being male was the unique protective factor in both waves. Other factors reflected different medical behaviours and the impact of comorbidities. Evidence of the effect of therapies adds valuable information that may drive future medical choices.

Source: Borgonovo F, Lovaglio PG, Mariani C, Berta P, Cossu MV, Rizzardini G, Vittadini G, Capetti AF. Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study. BMJ Open. 2024 Feb 6;14(2):e075185. doi: 10.1136/bmjopen-2023-075185. PMID: 38320835; PMCID: PMC10860093. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860093/ (Full text)

Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome

Abstract:

Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS).

A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances.

We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.

Source: Hamrefors V, Kahn F, Holmqvist M, Carlson K, Varjus R, Gudjonsson A, Fedorowski A, Ohlsson B. Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome. Sci Rep. 2024 Feb 9;14(1):3389. doi: 10.1038/s41598-024-53784-9. PMID: 38336892; PMCID: PMC10858216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858216/ (Full text)