Tag: long Covid

Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion

Abstract:

Serum-based ELISA (enzyme-linked immunosorbent assay) has been widely used to detect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, to date, no study has investigated patient urine as a biological sample to detect SARS-CoV-2 virus-specific antibodies. An in-house urine-based ELISA was developed using recombinant SARS-CoV-2 nucleocapsid protein.

The presence of SARS-CoV-2 antibodies in urine was established, with 94% sensitivity and 100% specificity for the detection of anti-SARS-CoV-2 antibodies with the urine-based ELISA and 88% sensitivity and 100% specificity with a paired serum-based ELISA. The urine-based ELISA that detects anti-SARS-CoV-2 antibodies is a noninvasive method with potential application as a facile COVID-19 immunodiagnostic platform, which can be used to report the extent of exposure at the population level and/or to assess the risk of infection at the individual level.

Source: Ludolf F, Ramos FF, Bagno FF, Oliveira-da-Silva JA, Reis TAR, Christodoulides M, Vassallo PF, Ravetti CG, Nobre V, da Fonseca FG, Coelho EAF. Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion. Sci Adv. 2022 May 13;8(19):eabn7424. doi: 10.1126/sciadv.abn7424. Epub 2022 May 13. PMID: 35559681; PMCID: PMC9106288. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106288/ (Full text)

Long COVID in the Long Run-23-Month Follow-up Study of Persistent Symptoms

Abstract:

Symptoms of long coronavirus disease (COVID) were found in 38% of 170 patients followed for a median of 22.6 months. The most prevalent symptoms were fatigue, affected taste and smell, and difficulties remembering and concentrating. Predictors for long COVID were older age and number of symptoms in the acute phase. Long COVID may take many months, maybe years, to resolve.

Source: Helmsdal G, Hanusson KD, Kristiansen MF, Foldbo BM, Danielsen ME, Steig BÁ, Gaini S, Strøm M, Weihe P, Petersen MS. Long COVID in the Long Run-23-Month Follow-up Study of Persistent Symptoms. Open Forum Infect Dis. 2022 Jun 6;9(7):ofac270. doi: 10.1093/ofid/ofac270. PMID: 35891696; PMCID: PMC9308378. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308378/ (Full text)

A comparison of pain, fatigue, and function between post–COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study

Abstract

A growing number of individuals report prolonged symptoms following acute COVID-19 infection, known as post-COVID-19 condition (post-COVID-19).

While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia (FMS) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS).

This study aimed to characterize multiple symptom domains in individuals reporting post-COVID-19 and compare its clinical phenotype to those with FMS and CFS.

A total of 707 individuals with a single or comorbid diagnosis of post-COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality. In all three diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported.

Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS.

The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared to post-COVID-19 alone.

In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.

Source: Haider S, Janowski AJ, Lesnak JB, Hayashi K, Dailey DL, Chimenti R, Frey-Law LA, Sluka KA, Berardi G. A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study. Pain. 2023 Feb 1;164(2):385-401. doi: 10.1097/j.pain.0000000000002711. Epub 2022 Jun 29. PMID: 36006296; PMCID: PMC9797623.  https://pubmed.ncbi.nlm.nih.gov/36006296/

Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID

Abstract:

Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions.

Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS.

Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.

Source: Zheng Liu, Claudia Hollmann, Sharada Kalanidhi, Arnhild Grothey, Samuel Keating, Irene Mena-Palomo, Stephanie Lamer, Andreas Schlosser, Agnes Kaiping, Carsten Scheller, Franziska Sotzny, Anna Horn, Carolin Nuernberger, Vladimir Cejka, Boshra Afshar, Thomas Bahmer, Stefan Schreiber, Joerg Janne Vehreschild, Olga Milljukov, Christian Schaefer, Luzie Kretzler, Thomas Keil, Jens-Peter Reese, Felizitas A Eichner, Lena Schmidbauer, Peter U Heuschmann, Stefan Stoerk, Caroline Morbach, Gabriela Riemekasten, Niklas Beyersdorf, Carmen Scheibenbogen, Robert K Naviaux, Marshall Williams, Maria E Ariza, Bhupesh Kumar Prusty. Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID. medRxiv 2023.06.23.23291827; doi: https://doi.org/10.1101/2023.06.23.23291827 https://www.medrxiv.org/content/10.1101/2023.06.23.23291827v1 (Full text available as PDF file)

Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies

Summary:

In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions.
Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.
Source: Danilo Buonsenso, Laura Martino, Rosa Morello, Francesco Mariani, Kelly Fearnley, Piero . Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies. The Lancet Microbe. Published: June 26, 2023. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(23)00115-5/fulltext (Full text)

Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

Persistent or recurrent cardiovascular symptoms have been identified as one of the hallmarks of long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The purpose of this study was to determine the prevalence and extent of cardiac abnormalities in patients referred for cardiac MRI due to clinical evidence of PASC. To investigate this, two tertiary care hospitals identified all patients who were referred for cardiac MRI under the suspicion of PASC in a 2-year period and retrospectively included them in this study.
Patients with previously known cardiac diseases were excluded. This resulted in a total cohort of 129 patients (63, 51% female; age 41 ± 16 years). The majority of patients (57%) showed normal cardiac results. No patient had active myocarditis or an acute myocardial infarction. However, 30% of patients had evidence of non-ischemic myocardial fibrosis, which exceeds the prevalence in the normal adult population and suggests that a possible history of myocarditis might explain persistent symptoms in the PASC setting.
Source: Halfmann MC, Luetkens JA, Langenbach IL, Kravchenko D, Wenzel P, Emrich T, Isaak A. Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection. Diagnostics. 2023; 13(13):2172. https://doi.org/10.3390/diagnostics13132172 https://www.mdpi.com/2075-4418/13/13/2172 (Full text)

The COVID-19 Pandemic and the $16 Trillion Virus

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic is the greatest threat to prosperity and well-being the US has encountered since the Great Depression. This Viewpoint aggregates mortality, morbidity, mental health conditions, and direct economic losses to estimate the total cost of the pandemic in the US on the optimistic assumption that it will be substantially contained by the fall of 2021. These costs far exceed those associated with conventional recessions and the Iraq War, and are similar to those associated with global climate change. However, increased investment in testing and contact tracing could have economic benefits that are at least 30 times greater than the estimated costs of the investment in these approaches.

Read the full text here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604733/

Also see: The Economic Cost of Long COVID: An Update: https://scholar.harvard.edu/files/cutler/files/long_covid_update_7-22.pdf

Source: Cutler DM, Summers LH. The COVID-19 Pandemic and the $16 Trillion Virus. JAMA. 2020;324(15):1495–1496. doi:10.1001/jama.2020.19759. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604733/ (Full text)

The Economic Cost of Long COVID: An Update

Relative to my earlier estimate with Lawrence Summers of the cost of long COVID of $2.6 trillion, the higher number here is higher: $3.7 trillion in total. The higher estimate is largely a result of the greater prevalence of long COVID than we had guessed at the time. There are about 10 times the number of people with long COVID as have died of COVID. Because long COVID is so new, there is uncertainty about all of the numbers involved in the calculations. Still, the costs here are conservative, based on only cases to date. The enormity of these costs implies that policy to address long COVID are urgently needed. With costs this high, virtually any amount spent on long COVID detection, treatment, and control would result in benefits far above what it costs.

Read the full text here: https://scholar.harvard.edu/files/cutler/files/long_covid_update_7-22.pdf

Note: See The COVID-19 Pandemic and the $16 Trillion Virus for background.

Source: David M. Cutler. The Economic Cost of Long COVID: An Update. Harvard University.

Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes

Introduction: Cognitive impairment is experienced by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of COVID-19 (PASC). Patients report difficulty remembering, concentrating, and making decisions. Our objective was to determine whether orthostatic hemodynamic changes were causally linked to cognitive impairment in these diseases.

Methods: This prospective, observational cohort study enrolled PASC, ME/CFS, and healthy controls. All participants underwent clinical evaluation and assessment that included brief cognitive testing before and after an orthostatic challenge. Cognitive testing measured cognitive efficiency which is defined as the speed and accuracy of subject’s total correct responses per minute. General linear mixed models were used to analyze hemodynamics and cognitive efficiency during the orthostatic challenge. Additionally, mediation analysis was used to determine if hemodynamic instability induced during the orthostatic challenge mediated the relationship between disease status and cognitive impairment.

Results: Of the 276 participants enrolled, 256 were included in this study (34 PASC, 71 < 4 year duration ME/CFS, 69 > 10 year ME/CFS duration, and 82 healthy controls). Compared to healthy controls, the disease cohorts had significantly lower cognitive efficiency scores immediately following the orthostatic challenge. Cognitive efficiency remained low for the >10 year ME/CFS 2 and 7 days after orthostatic challenge. Narrow pulse pressure less than 25% of systolic pressure occurred at 4 and 5 min into the orthostatic challenge for the PASC and ME/CFS cohorts, respectively. Abnormally narrow pulse pressure was associated with slowed information processing in PASC patients compared to healthy controls (−1.5, p = 0.04). Furthermore, increased heart rate during the orthostatic challenge was associated with a decreased procedural reaction time in PASC and < 4 year ME/CFS patients who were 40 to 65 years of age.

Discussion: For PASC patients, both their disease state and hemodynamic changes during orthostatic challenge were associated with slower reaction time and decreased response accuracy during cognitive testing. Reduced cognitive efficiency in <4 year ME/CFS patients was associated with higher heart rate in response to orthostatic stress. Hemodynamic changes did not correlate with cognitive impairment for >10 year ME/CFS patients, but cognitive impairment remained. These findings underscore the need for early diagnosis to mitigate direct hemodynamic and other physiological effects on symptoms of cognitive impairment.

Source: Day Heather, Yellman Brayden, Hammer Sarah, Rond Candace, Bell Jennifer, Abbaszadeh Saeed, Stoddard Greg, Unutmaz Derya, Bateman Lucinda, Vernon Suzanne D. Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes. Frontiers in Neuroscience, VOLUME=17, 2023. DOI=10.3389/fnins.2023.1203514. ISSN=1662-453X. https://www.frontiersin.org/articles/10.3389/fnins.2023.1203514 (Full text)

Impact of Covid-19 disease on thyroid function: longitudinal study

Abstract:

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic disease (Covid-19) affects thyroid function with different mechanisms: non-thyroidal illness syndrome (NTIS), direct infection of thyroid gland and cytokine storm. We provided the first description of painless atypical thyroiditis coexisting with NTIS in patients hospitalised for moderate-to-severe Covid-19 disease. We aimed to: 1) correlate thyroid dysfunction with Covid-19 disease severity; 2) follow the evolution of thyroid function over time.

Methods: Baseline (at hospital admittance) and longitudinal study of patients hospitalised for moderate-to-severe Covid-19 disease, without known history of thyroid disfunction, assessing serum thyroid function and autoantibodies, inflammatory markers and thyroid ultrasound scan (US). Patients showing at US focal hypoechoic areas suggestive for thyroiditis (thyroiditis-areas) also underwent thyroid 99mTc or I123 uptake scan.

Results: 183 Covid-19 patients were studied baseline, of whom 63 (34%) were already on steroid treatment before hospital admission, thus were not considered for TSH analysis. Decreased serum TSH positively correlated with albumin (P=0.02) and lymphocyte count (P<0.01) but not with C-reactive-protein (P=0.12) and interleukin-6 (P=0.10); TSH also progressively and inversely correlated to the need of oxygen support (P=0.02). Serum FT3 correlated positively with albumin (P<0.01) and inversely with D-dimer (P=0.02). Baseline thyroid US scan showed thyroiditis-areas in 18/65 (28%) patients, associated with reduced thyroid uptake at 99mTc/I123 scintigraphy in 14/17 (82%) cases. Thyroiditis-areas were more frequent among patients with baseline low TSH (6/10, 60%) compared with those with normal TSH (10/40, 25%, P=0.034). The patients with thyroiditis-areas also had higher baseline FT4 (P=0.018) and IL-6 (P=0.016) compared with those with normal thyroid US. Follow-up analysis was conducted in 75/183 (41%) patients; thyroid function and inflammatory markers normalized at all time-points in nearly all cases and no increase of thyroid autoantibodies positivity was observed. The thyroiditis-areas, even if often reduced in size, were still present after 6 and 12 months in 13/15 (87%) and 6/12 (50%) patients, respectively. After 9 months the thyroid uptake at 99mTc/I123 scintigraphy was still reduced in 4/6 (67%) patients, even if partially recovered (mean +28%) compared with baseline.

Conclusions: Thyroid dysfunction during moderate-to-severe Covid-19 disease is mild and transient, and thyroid hormones correlate with disease severity. Thyroiditis-areas at US occur frequently and may persist after one year, even if reduced in size; long-term consequences are unknown. The association of thyroiditis-areas with low TSH and high FT4 and IL-6 serum concentrations support the hypothesis of direct thyroid gland involvement in SARS-CoV-2 infection.

Source: Ilaria Muller, Matteo Varallo, Anita Daturi, Tiziana E Re, Davide Dazzi, Virgilio Longari, Andrea Gori, Giovanna Mantovani , Maura Arosio & Mario Salvi. Impact of Covid-19 disease on thyroid function: longitudinal study. Endocrine Abstracts (2022) 81 RC11.1 | DOI: 10.1530/endoabs.81.RC11.1 https://www.endocrine-abstracts.org/ea/0081/ea0081rc11.1