Tag: long covid recovery

Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome

Abstract:

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, “brain fog”, memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months.
Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression.
However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability.
Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.
Source: Akanchise T, Angelova A. Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome. Antioxidants. 2023; 12(2):393. https://doi.org/10.3390/antiox12020393 https://www.mdpi.com/2076-3921/12/2/393 (Full text)

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)

Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients

Abstract:

Introduction: Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined.
Population and Methods: Out of 105 contacts, 45 patients had two phone consultations separated by personalized support 15 and 22 months, respectively, after COVID infection. Self-reported symptoms, feelings of improvement and ability to return to work allowed us to determine the efficacy of the therapeutic strategy proposed.
Results: Unlike what was expected, many post-COVID-19 patients directly contacted the coordination team and had significant pre-existing comorbidities. Despite exercise, respiratory, olfactory rehabilitations, cognition/speech therapy and/or psychological support, the more frequent self-reported symptoms (fatigue, neurocognitive disorders, muscles and joint pain) did not resolve. However, dyspnea, anxiety and chest pain were significantly reduced. Finally, 2/3 of the patients felt some degree of improvement and returned to work either partially or fully, but 1/3 remained complaining of symptoms and out of work as late as 22 months after COVID occurrence. All patients greatly appreciated the second phone consultation.
Conclusions: In such complex situations, besides early and adapted rehabilitations and psychological help allowing better symptom management, relatively simple actions such as a phone call might be very useful to reduce patients’ feelings of abandonment.
Source: Van Wambeke E, Bezler C, Kasprowicz A-M, Charles A-L, Andres E, Geny B. Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients. Journal of Clinical Medicine. 2023; 12(3):741. https://doi.org/10.3390/jcm12030741 https://www.mdpi.com/2077-0383/12/3/741 (Full text)

Pediatric Post-Acute Sequelae of SARS-CoV-2 infection

Abstract:

Aim: Youth who have not recovered from COVID-19 have been referred to as having Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The goal of this study was to better understand which symptoms persisted since onset of infection and how these symptoms compare to symptoms experienced by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Method: A sample of 19 parents who had a child with PASC were recruited using social media to fill out a questionnaire detailing symptoms at two time points. The first time point included their child’s current symptoms and the second captured symptoms at initial infection. These participants were compared to a sample of 19 youth with ME/CFS.

Results: Findings indicated significant decreases among several immune, neuroendocrine, pain, post-exertional malaise (PEM), and COVID-19 Centers for Disease Control and Prevention (CDC) domain symptoms from time of acute infection to time of current reporting. Fatigue remained at a high level as did several symptoms within the sleep and PEM domains. Participants with ME/CFS had overall worse symptomatology when compared to participants with PASC, especially in the neurocognitive domain.

Conclusion: Most symptoms of those with PASC decline over time, but several remain at high levels, including fatigue. These findings are helpful in better understanding common symptom presentation profiles for youth with PASC and can be used to more adequately tailor diagnostic criteria and treatment strategies for youth.

Source: Leonard A. Jason, Madeline Johnson & Chelsea Torres (2023) Pediatric Post-Acute Sequelae of SARS-CoV-2 infection, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2162764 https://www.tandfonline.com/doi/abs/10.1080/21641846.2022.2162764

Long COVID: mechanisms, risk factors and recovery

Abstract:

New findings: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies.

Abstract: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery.

This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes.

The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve.

We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations.

Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

Source: Astin R, Banerjee A, Baker MR, Dani M, Ford E, Hull JH, Lim PB, McNarry M, Morten K, O’Sullivan O, Pretorius E, Raman B, Soteropoulos DS, Taquet M, Hall CN. Long COVID: mechanisms, risk factors and recovery. Exp Physiol. 2022 Nov 22. doi: 10.1113/EP090802. Epub ahead of print. PMID: 36412084. https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP090802 (Full text)

Mid-term Follow-Up chest CT findings in recovered COVID-19 patients with residual symptoms

Abstract:

Objectives: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups.

Methods: A total of 407 consecutive COVID-19 patients who were admitted to the XXXX and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest computer tomography study, which was evaluated for specific lung alterations and morphological patterns.

Results: The most frequently observed lung CT alterations, in order of frequency, were ground glass opacities (81%), linear opacities (74%), bronchiolectases (64,81%), and reticular opacities (63,88%). The most common morphological pattern was the nonspecific interstitial pneumonia pattern (63,88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29,62%).

Conclusions: Our work showed that recovered COVID-19 patients that were hospitalized and that exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations.

Advances in knowledge: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Source: Marchetti F, Izzi N, Donatelli A, Valentini A, Muzic SI, Dore R, Di Sabatino A, Perrone T, Falaschi F, Sabatini U, Ballesio A, Meloni F, Lettieri S, Mojoli F, Perlini S, Novati S, Pagani E, Klersy C, Bruno R, Preda L. Mid-term Follow-Up chest CT findings in recovered COVID-19 patients with residual symptoms. Br J Radiol. 2022 Nov 25:20220012. doi: 10.1259/bjr.20220012. Epub ahead of print. PMID: 36427055.  https://pubmed.ncbi.nlm.nih.gov/36427055/

Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study

Abstract:

With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity.

Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.

Source: Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, Scott JT, O’Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP. Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study. Nat Commun. 2022 Oct 12;13(1):5663. doi: 10.1038/s41467-022-33415-5. PMID: 36224173; PMCID: PMC9556711. https://www.nature.com/articles/s41467-022-33415-5 (Full text)

A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study

Abstract:

Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition.

To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19.

The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.

Source: Munblit D, Nicholson T, Akrami A, Apfelbacher C, Chen J, De Groote W, Diaz JV, Gorst SL, Harman N, Kokorina A, Olliaro P, Parr C, Preller J, Schiess N, Schmitt J, Seylanova N, Simpson F, Tong A, Needham DM, Williamson PR; PC-COS project steering committee. A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study. Lancet Respir Med. 2022 Jun 14:S2213-2600(22)00169-2. doi: 10.1016/S2213-2600(22)00169-2. Epub ahead of print. PMID: 35714658; PMCID: PMC9197249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197249/ (Full text)

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021

Abstract:

Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.

Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.

Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.

Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.

Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.

Source: Wulf Hanson S, Abbafati C, Aerts JG, Al-Aly Z, Ashbaugh C, Ballouz T, Blyuss O, Bobkova P, Bonsel G, Borzakova S, Buonsenso D, Butnaru D, Carter A, Chu H, De Rose C, Diab MM, Ekbom E, El Tantawi M, Fomin V, Frithiof R, Gamirova A, Glybochko PV, Haagsma JA, Javanmard SH, Hamilton EB, Harris G, Heijenbrok-Kal MH, Helbok R, Hellemons ME, Hillus D, Huijts SM, Hultström M, Jassat W, Kurth F, Larsson IM, Lipcsey M, Liu C, Loflin CD, Malinovschi A, Mao W, Mazankova L, McCulloch D, Menges D, Mohammadifard N, Munblit D, Nekliudov NA, Ogbuoji O, Osmanov IM, Peñalvo JL, Petersen MS, Puhan MA, Rahman M, Rass V, Reinig N, Ribbers GM, Ricchiuto A, Rubertsson S, Samitova E, Sarrafzadegan N, Shikhaleva A, Simpson KE, Sinatti D, Soriano JB, Spiridonova E, Steinbeis F, Svistunov AA, Valentini P, van de Water BJ, van den Berg-Emons R, Wallin E, Witzenrath M, Wu Y, Xu H, Zoller T, Adolph C, Albright J, Amlag JO, Aravkin AY, Bang-Jensen BL, Bisignano C, Castellano R, Castro E, Chakrabarti S, Collins JK, Dai X, Daoud F, Dapper C, Deen A, Duncan BB, Erickson M, Ewald SB, Ferrari AJ, Flaxman AD, Fullman N, Gamkrelidze A, Giles JR, Guo G, Hay SI, He J, Helak M, Hulland EN, Kereselidze M, Krohn KJ, Lazzar-Atwood A, Lindstrom A, Lozano R, Magistro B, Malta DC, Månsson J, Mantilla Herrera AM, Mokdad AH, Monasta L, Nomura S, Pasovic M, Pigott DM, Reiner RC, Reinke G, Ribeiro ALP, Santomauro DF, Sholokhov A, Spurlock EE, Walcott R, Walker A, Wiysonge CS, Zheng P, Bettger JP, Murray CJ, Vos T. A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021. medRxiv [Preprint]. 2022 May 27:2022.05.26.22275532. doi: 10.1101/2022.05.26.22275532. PMID: 35664995; PMCID: PMC9164454.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164454/ (Full text)