Tag: covid-19

Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms

Abstract:

Introduction: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.

Methods: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.

Results: The patients’ ages ranged from 34 to 79 years—with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.

Conclusion: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

Source: Thompson JS, Thornton AC, Ainger T and Garvy BA (2023) Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms. Front. Immunol. 13:1033651. doi: 10.3389/fimmu.2022.1033651 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033651/full (Full text)

Risks and burdens of incident dyslipidaemia in long COVID: a cohort study

Abstract:

Background: Non-clinical evidence and a few human studies with short follow-ups suggest increased risk of dyslipidaemia in the post-acute phase of COVID-19 (ie, >30 days after SARS-CoV-2 infection). However, detailed large-scale controlled studies with longer follow-ups and in-depth assessment of the risks and burdens of incident dyslipidaemia in the post-acute phase of COVID-19 are not yet available. We, therefore, aimed to examine the risks and 1-year burdens of incident dyslipidaemia in the post-acute phase of COVID-19 among people who survive the first 30 days of SARS-CoV-2 infection.

Methods: In this cohort study, we used the national health-care databases of the US Department of Veterans Affairs to build a cohort of 51 919 participants who had a positive COVID-19 test and survived the first 30 days of infection between March 1, 2020, and Jan 15, 2021; a non-infected contemporary control group (n=2 647 654) that enrolled patients between March 1, 2020, and Jan 15, 2021; and a historical control group (n=2 539 941) that enrolled patients between March 1, 2018, and Jan 15, 2019. Control groups had no evidence of SARS-CoV-2 infection, and participants in all three cohorts were free of dyslipidaemia before cohort enrolment. We then used inverse probability weighting using predefined and algorithmically-selected high dimensional variables to estimate the risks and 1-year burdens of incident dyslipidaemia, lipid-lowering medications use, and a composite of these outcomes. We reported two measures of risk: hazard ratios (HRs) and burden per 1000 people at 12 months. Additionally, we estimated the risks and burdens of incident dyslipidaemia outcomes in mutually exclusive groups based on the care setting of the acute infection (ie, participants who were non-hospitalised, hospitalised, or admitted to intensive care during the acute phase of SARS-CoV-2 infection).

Findings: In the post-acute phase of the SARS-CoV-2 infection, compared with the non-infected contemporary control group, those in the COVID-19 group had higher risks and burdens of incident dyslipidaemia, including total cholesterol greater than 200 mg/dL (hazard ratio [HR] 1·26, 95% CI 1·22-1·29; burden 22·46, 95% CI 19·14-25·87 per 1000 people at 1 year), triglycerides greater than 150 mg/dL (1·27, 1·23-1·31; 22·03, 18·85-25·30), LDL cholesterol greater than 130 mg/dL (1·24, 1·20-1·29; 18·00, 14·98-21·11), and HDL cholesterol lower than 40 mg/dL (1·20, 1·16-1·25; 15·58, 12·52-18·73). The risk and burden of a composite of these abnormal lipid laboratory outcomes were 1·24 (95% CI 1·21-1·27) and 39·19 (95% CI 34·71-43·73), respectively. There was also increased risk and burden of incident lipid-lowering medications use (HR 1·54, 95% CI 1·48-1·61; burden 25·50, 95% CI 22·61-28·50). A composite of any dyslipidaemia outcome (laboratory abnormality or lipid-lowering medications use) yielded an HR of 1·31 (95% CI 1·28-1·34) and a burden of 54·03 (95% CI 49·21-58·92). The risks and burdens of these post-acute outcomes increased in a graded fashion corresponding to the severity of the acute phase of COVID-19 infection (ie, whether patients were non-hospitalised, hospitalised, or admitted to intensive care). The results were consistent in analyses comparing the COVID-19 group to the non-infected historical control group.

Interpretation: Our findings suggest increased risks and 1-year burdens of incident dyslipidaemia and incident lipid-lowering medications use in the post-acute phase of COVID-19 infection. Post-acute care for those with COVID-19 should involve attention to dyslipidaemia as a potential post-acute sequela of SARS-CoV-2 infection.

Source: Xu E, Xie Y, Al-Aly Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2023 Feb;11(2):120-128. doi: 10.1016/S2213-8587(22)00355-2. Epub 2023 Jan 6. PMID: 36623520; PMCID: PMC9873268. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873268/ (Full text)

Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC)

Abstract:

With a growing number of patients entering the recovery phase following infection with SARS-CoV-2, understanding the long-term neurological consequences of the disease is important to their care. The neurological complications of post-acute sequelae of SARS-CoV-2 infection (NC-PASC) represent a myriad of symptoms including headaches, brain fog, numbness/tingling, and other neurological symptoms that many people report long after their acute infection has resolved.
Emerging reports are being published concerning COVID-19 and its chronic effects, yet limited knowledge of disease mechanisms has challenged therapeutic efforts. To address these issues, we review broadly the literature spanning 2020–2022 concerning the proposed mechanisms underlying NC-PASC, outline the long-term neurological sequelae associated with COVID-19, and discuss potential clinical interventions.
Source: Ong IZ, Kolson DL, Schindler MK. Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC). Biomedicines. 2023; 11(2):377. https://doi.org/10.3390/biomedicines11020377 https://www.mdpi.com/2227-9059/11/2/377

The emotional well-being of Long COVID patients in relation to their symptoms, social support and stigmatization in social and health services: a qualitative study

Abstract:

Background: Long COVID patients have experienced a decline in their quality of life due to, in part but not wholly, its negative emotional impact. Some of the most prevalent mental health symptoms presented by long COVID patients are anxiety, depression, and sleep disorders. As such, the need has arisen to analyze the personal experiences of these patients to understand how they are managing their daily lives while dealing with the condition. The objective of this study is to increase understanding about the emotional well-being of people diagnosed with long COVID.

Methods: A qualitative design was created and carried out using 35 patients, with 17 participants being interviewed individually and 18 of them taking part in two focus groups. The participating patients were recruited in November and December 2021 from Primary Health Care (PHC) centers in the city of Zaragoza (Northern Spain) and from the Association of Long COVID Patients in Aragon. The study topics were emotional well-being, social support networks, and experience of discrimination. All an inductive thematic content analyses were performed iteratively using NVivo software.

Results: The Long COVID patients identified low levels of self-perceived well-being due to their persistent symptoms, as well as limitations in their daily lives that had been persistent for many months. Suicidal thoughts were also mentioned by several patients. They referred to anguish and anxiety about the future as well as a fear of reinfection or relapse and returning to work. Many of the participants reported that they have sought the help of a mental health professional. Most participants identified discriminatory situations in health care.

Conclusions: It is necessary to continue researching the impact that Long COVID has had on mental health, as well as to provide Primary Health Care professionals with evidence that can guide the emotional treatment of these patients.

Source: Samper-Pardo M, Oliván-Blázquez B, Magallón-Botaya R, Méndez-López F, Bartolomé-Moreno C, León-Herrera S. The emotional well-being of Long COVID patients in relation to their symptoms, social support and stigmatization in social and health services: a qualitative study. BMC Psychiatry. 2023 Jan 25;23(1):68. doi: 10.1186/s12888-022-04497-8. PMID: 36698111; PMCID: PMC9875186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875186/ (Full text)

What interventions or best practice are there to support people with Long COVID, or similar post-viral conditions or conditions characterised by fatigue, to return to normal activities: a rapid review

Abstract:

Previous research has categorised symptoms of COVID-19 / Long COVID into 12 thematic areas including: fever, myalgia, fatigue, impaired cognitive function, and that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life.

Our aim was to review the evidence for interventions or best practice to support people with Long COVID, or similar post-viral conditions characterised by fatigue, to return to normal activities.

Evidence was included from guidelines, systematic reviews (SR), and primary studies. The primary studies focussed on Long COVID (LC) indicated that there should be a needs-based focus to care for those with LC.

Consideration should be given to individuals living with LC in the same way as people with disabilities are accommodated in terms of workplace adjustment.

Two SRs indicated that non-pharmaceutical interventions (NPIs) for patients with LC or chronic fatigue syndrome could help improve function for activities of daily life. However, the third, most recent SR, concluded that there is a lack of robust evidence for NPIs.

LC fatigue management methods may be beneficial under certain conditions. One SR reported work capability as an outcome however they did not find any studies which evaluated the impact of interventions on return to work/ normal life.

One primary study, on individuals with CFS, described a written self-management programme. Following this intervention there was an 18% increase in the number of patients in employment.

Policy and practice implications: Long COVID is still being established as a post-viral condition with many symptoms. Patient-centred treatment options such as occupational therapy, self-management therapy and talking therapy may be considered in the same way as for other debilitating conditions. Return-to-work accommodations are needed for all workers unable to return to full-time employment.

Due to the nature of the studies included, there was little reported evidence of effectiveness of getting individuals back into their normal activities.

Source: Llinos Haf Spencer, Annie Hendry, Abraham Makanjuola, Bethany F Anthony, Jacob Davies, Kalpa Pisavadia, Dyfrig Hughes, Deb Fitzsimmons, Clare Wilkinson, Rhiannon Tudor Edwards, Ruth Lewis, Alison Cooper, Adrian Edwards. What interventions or best practice are there to support people with Long COVID, or similar post-viral conditions or conditions characterised by fatigue, to return to normal activities: a rapid review. medRxiv 2023.01.24.23284947; doi: https://doi.org/10.1101/2023.01.24.23284947 (Full text)

Chronic viral coinfections differentially affect the likelihood of developing long COVID

Abstract:

BACKGROUND. The presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.

METHODS. In a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.

RESULTS. We observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen–diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen–diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).

CONCLUSION. Overall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.

Source: Peluso MJ, Deveau TM, Munter SE, Ryder D, Buck A, Beck-Engeser G, Chan F, Lu S, Goldberg SA, Hoh R, Tai V, Torres L, Iyer NS, Deswal M, Ngo LH, Buitrago M, Rodriguez A, Chen JY, Yee BC, Chenna A, Winslow JW, Petropoulos CJ, Deitchman AN, Hellmuth J, Spinelli MA, Durstenfeld MS, Hsue PY, Kelly JD, Martin JN, Deeks SG, Hunt PW, Henrich TJ. Chronic viral coinfections differentially affect the likelihood of developing long COVID. J Clin Invest. 2023 Feb 1;133(3):e163669. doi: 10.1172/JCI163669. PMID: 36454631. https://www.jci.org/articles/view/163669 (Full text)

Cardiac Autonomic Function in Long COVID-19 Using Heart Rate Variability: An Observational Cross-Sectional Study

Abstract:

Background: Heart rate variability is a non-invasive, measurable, and established autonomic nervous system test. Long-term COVID-19 sequelae are unclear; however, acute symptoms have been studied.

Objectives: To determine autonomic cardiac differences between long COVID-19 patients and healthy controls and evaluate associations among symptoms, comorbidities, and laboratory findings.

Methods: This single-center study included long COVID-19 patients and healthy controls. The heart rate variability (HRV), a quantitative marker of autonomic activity, was monitored for 24 h using an ambulatory electrocardiogram system. HRV indices were compared between case and control groups. Symptom frequency and inflammatory markers were evaluated. A significant statistical level of 5% (p-value 0.05) was adopted.

Results: A total of 47 long COVID-19 patients were compared to 42 healthy controls. Patients averaged 43.8 (SD14.8) years old, and 60.3% were female. In total, 52.5% of patients had moderate illness. Post-exercise dyspnea was most common (71.6%), and 53.2% lacked comorbidities. CNP, D-dimer, and CRP levels were elevated (p-values of 0.0098, 0.0023, and 0.0015, respectively). The control group had greater SDNN24 and SDANNI (OR = 0.98 (0.97 to 0.99; p = 0.01)). Increased low-frequency (LF) indices in COVID-19 patients (OR = 1.002 (1.0001 to 1.004; p = 0.030)) and high-frequency (HF) indices in the control group (OR = 0.987 (0.98 to 0.995; p = 0.001)) were also associated.

Conclusions: Patients with long COVID-19 had lower HF values than healthy individuals. These variations are associated with increased parasympathetic activity, which may be related to long COVID-19 symptoms and inflammatory laboratory findings.

Source: Menezes Junior ADS, Schröder AA, Botelho SM, Resende AL. Cardiac Autonomic Function in Long COVID-19 Using Heart Rate Variability: An Observational Cross-Sectional Study. J Clin Med. 2022 Dec 22;12(1):100. doi: 10.3390/jcm12010100. PMID: 36614901; PMCID: PMC9821736. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821736/ (Full text)

Vascular “Long COVID”: A New Vessel Disease?

Abstract:

Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as “Long Covid (LC)” disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first “endotheliitis,” is often followed by production of “Neutrophil Extracellular Trap,” and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis.

In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible “LC” disease.

Source: Zanini G, Selleri V, Roncati L, Coppi F, Nasi M, Farinetti A, Manenti A, Pinti M, Mattioli AV. Vascular “Long COVID”: A New Vessel Disease? Angiology. 2023 Jan 18:33197231153204. doi: 10.1177/00033197231153204. Epub ahead of print. PMID: 36652923. https://pubmed.ncbi.nlm.nih.gov/36652923/

Improvement of Long COVID symptoms over one year

Abstract:

Importance: Early and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.

Methods: This prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of >3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.

Participants: Patients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.

Results: At baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.

Conclusion and relevance: There were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.

Source: Oliveira CR, Jason LA, Unutmaz D, Bateman L, Vernon SD. Improvement of Long COVID symptoms over one year. Front Med (Lausanne). 2023 Jan 9;9:1065620. doi: 10.3389/fmed.2022.1065620. PMID: 36698810; PMCID: PMC9868805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868805/ (Full text)

Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial

Abstract:

Background: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug.

Methods: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test.

Results: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort.

Conclusions: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials.

Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.

Source: Kjellberg A, Hassler A, Boström E, El Gharbi S, Al-Ezerjawi S, Kowalski J, Rodriguez-Wallberg KA, Bruchfeld J, Ståhlberg M, Nygren-Bonnier M, Runold M, Lindholm P. Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial. BMC Infect Dis. 2023 Jan 20;23(1):33. doi: 10.1186/s12879-023-08002-8. PMID: 36670365; PMCID: PMC9854077. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854077/ (Full text)