Tag: long Covid

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

Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID

Abstract:

Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID.

In the present study, we measured serum TRY, TRYCATs, insulin resistance (using the Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, and anxiety symptoms in 90 Long COVID patients, 3–10 months after remission of acute infection.

We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome.

Three Long COVID biomarkers (CRP, KYN/TRY, and IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, and IR (Long COVID), and PBT and SpO2 (acute COVID-19).

In conclusion, the physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID, and lowered plasma tryptophan and increased kynurenine may contribute to these effects.

Source: Al-Hakeim HK, Khairi Abed A, Rouf Moustafa S, Almulla AF, Maes M. Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID. Front Mol Neurosci. 2023 Jun 2;16:1194769. doi: 10.3389/fnmol.2023.1194769. PMID: 37333619; PMCID: PMC10272345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272345/ (Full text)

Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis

Abstract:

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well-documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties. This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a strikingly similar syndrome.

In the majority of the PTLDS studies, at least four of the six major symptoms of ME/CFS were also noted, including substantial impairment in activity level and fatigue for more than 6 months, post-exertional malaise, and unrefreshing sleep. In one of the included PTLDS articles, 26 of the 29 ME/CFS symptoms were noted. This study adds to the expanding literature on the post-active phase of infection syndromes, which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

Key points

  • This systematic review uses qualitative analysis to compare posttreatment Lyme disease syndrome to myalgic encephalitis/chronic fatigue syndrome, both of which are post-active phases of infection syndromes.
  • The result of this review suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

Source: Bai, NA, Richardson, CS. Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis. Chronic Dis Transl Med. 2023; 1– 8. doi:10.1002/cdt3.74 https://onlinelibrary.wiley.com/doi/full/10.1002/cdt3.74 (Full text)

Vagus Nerve Dysfunction in the Post-COVID-19 Condition

Abstract:

Background: The post-COVID-19 condition (PCC) is a disabling syndrome affecting 5-15% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some of the PCC symptoms, including persistent dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances or neurocognitive complaints.

Methods: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n=30) and compared them to subjects fully recovered from acute COVID-19 (n=14) and individuals never infected with SARS-CoV-2 (n=16), matched by age and sex. We evaluated the structure and function of the vagus nerve, including dysphonia, dysphagia, and dysautonomia tests, and evaluated the structure and function of respiratory muscles with vagus nerve innervation.

Findings: Participants were mostly (80%) women with median 44 years of age. Their most prevalent symptoms were cognitive dysfunction (83%), dyspnea (80%) and tachycardia (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (mean ± SD left vagus nerve cross-sectional area: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2, p=0.080), flattened diaphragmatic curve (47% vs 6% vs 14%, p=0.007), reduced esophageal peristalsis (34% vs 0% vs 21%, p=0.020), gastroesophageal reflux (34% vs 19% vs 7%, p=0.130), hiatal hernia (25% vs 0% vs 7%, p=0.050) and reduced maximal inspiratory pressure in functional respiratory tests (62% vs. 6% vs. 17%, p ≤0.001).

Interpretation: Vagus nerve dysfunction has a central pathogenic role in the pathophysiology of the post-COVID condition.

Source: Lladós, Gemma and Massanella, Marta and Coll-Fernández, Roser and Rodríguez, Raúl and Hernández, Electra and Lucente, Giuseppe and López, Cristina and Loste, Cora and Santos, José Ramón and España-Cueto, Sergio and Nevot, Maria and Muñoz-López, Francisco and Arrieta, Sandra Silva and Brander, Christian and Durà, Maria José and Cuadras, Patricia and Bechini, Jordi and Tenesa, Montserrat and Martinez-Piñeiro, Alicia and Herrero, Cristina and Chamorro, Anna and Garcia, Anna and Grau, Eulalia and Clotet, Bonaventura and Paredes, Roger and Mateu, Lourdes and Unit, Germans Trias Long-COVID, Vagus Nerve Dysfunction in the Post-COVID-19 Condition. Available at SSRN: https://ssrn.com/abstract=4479598 or http://dx.doi.org/10.2139/ssrn.4479598

“We’re drowning and we’re alone”: a qualitative study of the lived experience of people experiencing persistent post-COVID-19 symptoms

Abstract:

Background: The “long tail” of the COVID-19 pandemic will be reflected in disabling symptoms that persist, fluctuate or recur for extended periods for an estimated 20%-30% of those who had a SARS-CoV-2 infection; development of effective interventions to address these symptoms must account for the realities faced by these patients. We sought to describe the lived experience of patients living with persistent post-COVID-19 symptoms.

Methods: We conducted a qualitative study, using interpretive description, of the lived experiences of adults experiencing persistent post-COVID-19 symptoms. We collected data from in-depth, semistructured virtual focus groups in February and March 2022. We used thematic analysis to analyze the data and met with several participants twice for respondent validation.

Results: The study included 41 participants (28 females) from across Canada with a mean age of 47.9 years and mean time since initial SARS-CoV-2 infection of 15.8 months. Four overarching themes were identified: the unique burdens of living with persistent post-COVID-19 symptoms; the complex nature of patient work in managing symptoms and seeking treatment during recovery; erosion of trust in the health care system; and the process of adaptation, which included taking charge and transformed self-identity.

Interpretation: Living with persistent post-COVID-19 symptoms within a health care system ill-equipped to provide needed resources profoundly challenges the ability of survivors to restore their well-being. Whereas policy and practice increasingly emphasize the importance of self-management within the context of post-COVID-19 symptoms, new investments that enhance services and support patient capacity are required to promote better outcomes for patients, the health care system and society.

Source: Goodridge D, Lowe TN, Cai S, Herriot FN, Silverberg RV, Heynen M, Hall KC, Peters J, Butcher S, Oyedokun T. “We’re drowning and we’re alone”: a qualitative study of the lived experience of people experiencing persistent post-COVID-19 symptoms. CMAJ Open. 2023 Jun 13;11(3):E504-E515. doi: 10.9778/cmajo.20220205. PMID: 37311595; PMCID: PMC10270655. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270655/ (Full text)