Tag: 2022

Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients

Abstract:

After acute infection with the SARS-CoV-2 virus, a considerable number of patients remains symptomatic with pathological changes in various organ systems. This study aimed to relate the physical and mental burden of symptoms of long COVID patients to the findings of a somatic evaluation.

In patients with persistent long COVID symptoms three months after acute infection we assessed physical and mental health status using the SF-36 questionnaire. The cohort was dichotomised by the results (upper two quartiles vs. lower to quartiles) and compared with regard to transthoracic echocardiography, body plethysmography (including diffusion capacity), capillary blood gas analysis and 6-min walk test (6-MWT). From February 22 to September 13, 2021, 463 patients were prospectively examined, of which 367 completed the SF-36 questionnaire. A positive correlation between initial disease severity (need for hospitalization, intensive care medicine) and resulting symptom burden at follow-up could be demonstrated.

Patients with impaired subjective physical and mental status were significantly more likely to be women. There was a significant correlation between symptom severity and reduced exercise tolerance in the 6-MWT (495.6 ± 83.7 m vs 549.7 ± 71.6 m, p < 0.001) and diffusion capacity for carbon monoxide (85.6 ± 14.3% of target vs 94.5 ± 14.4, p < 0.001). In long COVID patients, initial disease severity is correlated with symptom burden after at least 3 months of follow-up. Highly symptomatic long COVID patients show impaired diffusion capacity and 6-MWT despite average or mildly affected mechanical lung parameters. It must be further differentiated whether this corresponds to a transient functional impairment or whether it is a matter of defined organ damage.

Source: Kersten, J., Wolf, A., Hoyo, L. et al. Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients. Sci Rep 12, 8801 (2022). https://doi.org/10.1038/s41598-022-12839-5  https://www.nature.com/articles/s41598-022-12839-5 (Full text)

Long COVID and the Autonomic Nervous System: The Journey from Dysautonomia to Therapeutic Neuro-Modulation through the Retrospective Analysis of 152 Patients

Abstract:

Introduction. The severity and prevalence of Post-Acute COVID-19 Sequela (PACS) or long-COVID syndrome (long COVID) should not be a surprise. Long-COVID symptoms may be explained by oxidative stress and parasympathetic and sympathetic (P&S) dysfunction. This is a retrospective, hypothesis generating, outcomes study.
Methods. From two suburban practices in northeastern United States, 152 long COVID patients were exposed to the following practices: (1) first, they were P&S tested (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) prior to being infected with COVID-19 due to other causes of autonomic dysfunction; (2) received a pre-COVID-19 follow-up P&S test after autonomic therapy; (3) then, they were infected with COVID-19; (4) P&S tested within three months of surviving the COVID-19 infection with long-COVID symptoms; and, finally, (5) post-COVID-19, follow-up P&S tested, again, after autonomic therapy. All the patients completed autonomic questionnaires with each test. This cohort included 88 females (57.8%), with an average age of 47.0 years (ranging from 14 to 79 years), and an average BMI of 26.9 #/in2. Results. More pre-COVID-19 patients presented with sympathetic withdrawal than parasympathetic excess. Post-COVID-19, these patients presented with this ratio reversed and, on average, 49.9% more autonomic symptoms than they did pre-COVID-19.
Discussion. Both parasympathetic excess and sympathetic withdrawal are separate and treatable autonomic dysfunctions and autonomic treatment significantly reduces the prevalence of autonomic symptoms.
Conclusion. SARS-CoV-2, via its oxidative stress, can lead to P&S dysfunction, which, in turn, affects the control and coordination of all systems throughout the whole body and may explain all of the symptoms of long-COVID syndrome. Autonomic therapy leads to positive outcomes and patient quality of life may be restored.
Source: Colombo J, Weintraub MI, Munoz R, Verma A, Ahmad G, Kaczmarski K, Santos L, DePace NL. Long COVID and the Autonomic Nervous System: The Journey from Dysautonomia to Therapeutic Neuro-Modulation through the Retrospective Analysis of 152 Patients. NeuroSci. 2022; 3(2):300-310. https://doi.org/10.3390/neurosci3020021 https://www.mdpi.com/2673-4087/3/2/21/htm (Full text)

Long COVID after breakthrough SARS-CoV-2 infection

Abstract:

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear.

In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders.

The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

Source: Al-Aly, Z., Bowe, B. & Xie, Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med (2022). https://doi.org/10.1038/s41591-022-01840-0  https://www.nature.com/articles/s41591-022-01840-0 (Full text)

Impaired Vagal Activity in Long-COVID-19 Patients

Abstract:

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction.

To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p &lt; 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p &lt; 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820).

Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.

Source: Acanfora D, Nolano M, Acanfora C, Colella C, Provitera V, Caporaso G, Rodolico GR, Bortone AS, Galasso G, Casucci G. Impaired Vagal Activity in Long-COVID-19 Patients. Viruses. 2022 May 13;14(5):1035. doi: 10.3390/v14051035. PMID: 35632776; PMCID: PMC9147759. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147759/ (Full text)

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report

Abstract:

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Source: Sabino JS, Amorim MR, de Souza WM, Marega LF, Mofatto LS, Toledo-Teixeira DA, Forato J, Stabeli RG, Costa ML, Spilki FR, Sabino EC, Faria NR, Benites BD, Addas-Carvalho M, Stucchi RSB, Vasconcelos DM, Weaver SC, Granja F, Proenca-Modena JL, Vilela MMDS. Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report. Viruses. 2022 May 13;14(5):1042. doi: 10.3390/v14051042. PMID: 35632784; PMCID: PMC9143223. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143223/ (Full text)

Neurological Sequelae of COVID-19

Abstract:

Background: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19.

The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders.

Objective: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments.

Methods: A literature review was carried out by the authors using PubMed with the search terms “COVID-19” and “Neurology”, “Neurological Manifestations”, “Neuropsychiatric Manifestations”, “Stroke”, “Encephalopathy”, “Headache”, “Guillain-Barre syndrome”, “Depression”, “Anxiety”, “Encephalitis”, “Seizure”, “Spasm”, and “ICUAW”. Another search was carried out for “Long-COVID” and “Post-Acute COVID-19” and “Neurological Manifestations” or “Neuropsychiatric Manifestations”. Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients.

Results: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Source: Ahmad SJ, Feigen CM, Vazquez JP, Kobets AJ, Altschul DJ. Neurological Sequelae of COVID-19. J Integr Neurosci. 2022 Apr 6;21(3):77. doi: 10.31083/j.jin2103077. PMID: 35633158. https://www.imrpress.com/journal/JIN/21/3/10.31083/j.jin2103077/htm (Full text)

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study

Abstract:

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample.

This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures).

Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006).

We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Source: Damiano RF, Neto DB, Oliveira JVR, Magalhães Santos J, Alves JVR, Guedes BF, Nitrini R, de Araújo AL, Oliveira M, Brunoni AR, Voegels RL, Bento RF, Busatto G, Miguel EC, Forlenza OV, de Rezende Pinna F; HCFMUSP COVID-19 study group. Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study. Eur Arch Psychiatry Clin Neurosci. 2022 May 28:1–9. doi: 10.1007/s00406-022-01427-3. Epub ahead of print. PMID: 35633395; PMCID: PMC9142732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142732/ (Full text)

Cardiometabolic syndrome — an emergent feature of Long COVID?

Large-scale clinical studies on the post-infectious impacts of SARS-CoV-2 have suggested that patients who have recovered from acute infection have increased risk for cardiometabolic syndrome-associated morbidities such as diabetes, chronic kidney disease and heart failure. Initial studies have taken the first steps towards unravelling the molecular processes that may be driving these findings, including the role of immune and inflammatory factors, but a comprehensive aetiology remains unclear. Given that cardiometabolic syndrome progression in patients with Long COVID may pose a significant global health and economic burden post pandemic, there is an emergent need to identify therapeutic targets and treatment options.

Read the rest of this article HERE.

Source: Frere, J.J., tenOever, B.R. Cardiometabolic syndrome — an emergent feature of Long COVID?. Nat Rev Immunol (2022). https://doi.org/10.1038/s41577-022-00739-8 (Full text)

One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study

Abstract:

Purpose: Globally, concerns have grown regarding the long-term effects of novel coronavirus disease (COVID-19) infection. Therefore, we evaluated the long-term course of persistent symptoms and patient quality of life.

Materials and methods: This prospective cohort study was conducted at a single tertiary university hospital from August 31, 2020 to March 29, 2021 with adult patients followed at 6 and 12 months after acute COVID-19 symptom onset or diagnosis. Clinical characteristics, self-reported symptoms, EuroQol 5 dimension 5 level (EQ5D-5L) index scores, Korean version of the Patient Health Questionnaire-9 (PHQ-9), Korean version of the Posttraumatic Stress Disorder Checklist-5 (PCL-5-K), and Generalized Anxiety Disorder-7 (GAD-7) were investigated. Symptom persistent or non-persistent groups were defined according to persistency of COVID-19 related symptoms or signs after acute COVID-19 infection, respectively.

Results: Of all 235 patients, 170 (64.6%) patients were eligible for analysis. The median age was 51 (interquartile range, 37-61) years old, and 102 patients were female (60.0%). After 12 months from acute COVID-19 infection, in total, 83 (48.8%) patients still suffered from COVID-19-related symptoms. The most common symptoms included amnesia (24.1%), insomnia (14.7%), fatigue (13.5%), and anxiety (12.9%). Among the five EQ5D-5L categories, the average value of anxiety or depression was the most predominant. PHQ-9 and PCL-5-K scores were statistically higher in the COVID-19-related symptom persistent group than the non-persistent group (p=0.001). However, GAD-7 scores showed no statistical differences between the two groups (p=0.051).

Conclusion: Neuropsychiatric symptoms were the major COVID-19-related symptoms after 12 months from acute COVID-19 infection, reducing quality of life.

Source: Kim Y, Kim SW, Chang HH, Kwon KT, Hwang S, Bae S. One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study. Yonsei Med J. 2022 Jun;63(6):499-510. doi: 10.3349/ymj.2022.63.6.499. PMID: 35619573. https://eymj.org/DOIx.php?id=10.3349/ymj.2022.63.6.499 (Full text)

Use of linked patient data to assess the effect of Long-COVID on system-wide healthcare utilisation

Abstract:

Background: Within the relatively early stages of the COVID-19 pandemic, there had been an awareness of the potential longer-term effects of infection (so called Long-COVID) but little was known of the ongoing demands such patients may place on healthcare services.

Objective: To investigate whether COVID-19 illness is associated with increased post-acute healthcare utilisation.

Method: Using linked data from primary care, secondary care, mental health and community services, activity volumes were compared across the 3 months preceding and proceeding COVID-19 diagnoses for 7,791 individuals, with a distinction made between whether or not patients were hospitalised for treatment. Differences were assessed against those of a control group containing individuals who had not received a COVID-19 diagnosis. All data were sourced from the authors’ healthcare system in South West England.

Results: For hospitalised COVID-19 cases, a statistically significant increase in non-elective admissions was identified for males and females <65 years. For non-hospitalised cases, statistically significant increases were identified in GP Doctor and Nurse attendances and GP prescriptions (males and females, all ages); Emergency Department attendances (females <65 years); Mental Health contacts (males and females ≥65 years); and Outpatient consultations (males ≥65 years).

Conclusion: There is evidence of an association between positive COVID-19 diagnosis and increased post-acute activity within particular healthcare settings. Linked patient-level data provides information that can be useful to understand ongoing healthcare needs resulting from Long-COVID, and support the configuration of Long-COVID pathways of care.

Source: Murch BJ, Hollier SE, Kenward C, Wood RM. Use of linked patient data to assess the effect of Long-COVID on system-wide healthcare utilisation. Health Inf Manag. 2022 May 25:18333583221089915. doi: 10.1177/18333583221089915. Epub ahead of print. PMID: 35615791. https://pubmed.ncbi.nlm.nih.gov/35615791/