Tag: long covid symptoms

Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors

Abstract:

Objective: The aim of this study was to investigate the association between serological biomarkers at the acute phase of infection at hospital admission with the development of long-term post-COVID fatigue and dyspnea.

Methods: A cohort study including patients hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the outbreak (from March 20 to June 30, 2020) was conducted. Hospitalization data, clinical data, and eleven serological biomarkers were systematically collected at hospital admission. Patients were scheduled for an individual telephone interview after hospital discharge for collecting data about the presence of post-COVID fatigue and dyspnea.

Results: A total of 412 patients (age: 62 years, standard deviation: 15 years; 47.5% women) were assessed with a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID fatigue and dyspnea was 72.8% and 17.2% at 6 months and 45.4% and 13.6% at 12 months after hospital discharge, respectively. Patients exhibiting post-COVID fatigue at 6 or 12 months exhibited a lower hemoglobin level, higher lymphocyte count, and lower neutrophil and platelets counts (all, p < 0.05), whereas those exhibiting post-COVID dyspnea at 6 or 12 months had a lower platelet count and lower alanine transaminase, aspartate transaminase, and lactate dehydrogenase (LDH) levels (all, p < 0.05) than those not developing post-COVID fatigue or dyspnea, respectively. The multivariate regression analyses revealed that a lower platelet count and lower LDH levels were associated but just explaining 4.5% of the variance, of suffering from post-COVID fatigue and dyspnea, respectively.

Conclusion: Some serological biomarkers were slightly different in patients exhibiting post-COVID fatigue or dyspnea, but they could not explain the long-COVID problems in those patients.

Source: Fernández-de-Las-Peñas C, Ryan-Murua P, Rodríguez-Jiménez J, Palacios-Ceña M, Arendt-Nielsen L, Torres-Macho J. Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors. Respiration. 2022 Apr 5:1-8. doi: 10.1159/000524042. Epub ahead of print. PMID: 35381597. https://www.karger.com/Article/FullText/524042 (Full text)

Coronary microvascular health in patients with prior covid-19 infection: implications for long-covid syndrome

Background: SARS-CoV-2 infection has been shown to directly infect coronary vascular endothelium, causing inflammation and plaque instability. We aimed to assess the vascular health of patients with prior COVID-19 using Positron emission tomography (PET) derived coronary flow reserve (CFR).

Methods: A prospective cohort of consecutive patients with PCR confirmed prior COVID-19 infection undergoing clinically indicated PET myocardial perfusion imaging were included and compared to patients with no prior COVID19. CFR was determined by PET and microvascular dysfunction (CMD) was defined as CFR<2.

Results: The study population consisted of 2316 patients (4.4% prior COVID 19, 52% male, mean age 67±12 years, 55% hypertensive, 32% diabetic, 41% dyslipidemia). The mean duration between COVID19 diagnosis and PET was 191 (±131) days. CMD was more prevalent in those with prior COVID19 (58% vs 46%, p=0.012). After adjusting for baseline and clinical characteristics, patients with prior COVID19 had statistically significant higher odds of CMD (OR 1.8, p=0.008). Results were consistent in subgroups of patients with no clinical risk factors and normal stress tests.

Conclusion: Our analysis shows that patients with prior COVID19 have higher rates of CMD. This may in part explain the long-COVID symptoms. The prognostic implications of these findings need to be determined.

Source: Ahmed A, Saad J, Han Y, et al. CORONARY MICROVASCULAR HEALTH IN PATIENTS WITH PRIOR COVID-19 INFECTION: IMPLICATIONS FOR LONG-COVID SYNDROME. J Am Coll Cardiol. 2022 Mar, 79 (9_Supplement) 1822. https://doi.org/10.1016/S0735-1097(22)02813-3

Cardiovascular impairment in long covid one year post-sars-cov-2 infection

Background: Long Covid is associated with multi-organ inflammation, hypercoagulability, and several symptoms (fatigue, dyspnoea etc). Varying levels of cardiac involvement have been reported by cardiac magnetic resonance (CMR). We now describe longitudinal cardiovascular impairment in patients with Long Covid at 6 and 12 months post-SARS-CoV-2 infection.

Methods: 524 participants with Long Covid underwent a baseline scan at 6 months post infection (ClinicalTrials.gov: NCT04369807) and were rescanned 12 months post-infection if abnormal findings were reported at baseline. CMR (T1 and T2, cardiac mass, volumes, function, and strain), along with multi-organ MRI and blood samples were collected. Cardiovascular impairment was defined as one or more of: low left ventricular ejection fraction (LVEF), high left ventricular end diastolic volume (LVEDV), elevated native T1 in 3 or more cardiac segments. A significant longitudinal change was reported if greater than the repeatability coefficients derived from a population of 92 healthy controls.

Results: In 70 patients with cardiovascular impairment and Long Covid at baseline, 48 had complete paired data at 1 year, and of those 54% had not fully resolved. 19 (27%) patients with cardiovascular impairment had required hospitalization for acute COVID-19. Troponin or BNP were not predictive of CMR findings; however, hospitalization at the acute stage, male sex, kidney fibroinflammation and serum bicarbonate were. Individual symptoms were not specific to cardiovascular impairment or disease course.

Conclusion: CMR shows that cardiovascular impairment persists in Long Covid in some patients beyond 12 months post infection; however, this impairment may have pre-existing origin. Although there is an association with acute COVID-19 hospitalisation, male gender and high serum bicarbonate were predictive of cardiovascular impairment, subtypes of disease (based on symptoms, examination, and investigations) are yet to be established. Therefore, interventional trials with pre-specified subgroup analysis are required to inform therapeutic options.

Source: Roca-Fernandez A, Wamil M, Telford A, et al. CARDIOVASCULAR IMPAIRMENT IN LONG COVID ONE YEAR POST-SARS-COV-2 INFECTION. J Am Coll Cardiol. 2022 Mar, 79 (9_Supplement) 1312. https://doi.org/10.1016/S0735-1097(22)02303-8

Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort

Abstract:

About 10% of people infected by severe acute respiratory syndrome coronavirus 2 experience post COVID-19 disease. We analysed data from 968 adult patients (5350 person-months) with a confirmed infection enroled in the ComPaRe long COVID cohort, a disease prevalent prospective e-cohort of such patients in France. Day-by-day prevalence of post COVID-19 symptoms was determined from patients’ responses to the Long COVID Symptom Tool, a validated self-reported questionnaire assessing 53 symptoms.

Among patients symptomatic after 2 months, 85% still reported symptoms one year after their symptom onset. Evolution of symptoms showed a decreasing prevalence over time for 27/53 symptoms (e.g., loss of taste/smell); a stable prevalence over time for 18/53 symptoms (e.g., dyspnoea), and an increasing prevalence over time for 8/53 symptoms (e.g., paraesthesia). The disease impact on patients’ lives began increasing 6 months after onset. Our results are of importance to understand the natural history of post COVID-19 disease.

Source: Tran VT, Porcher R, Pane I, Ravaud P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat Commun. 2022 Apr 5;13(1):1812. doi: 10.1038/s41467-022-29513-z. PMID: 35383197. https://www.nature.com/articles/s41467-022-29513-z (Full text)

COVID-19 patients require multi-disciplinary rehabilitation approaches to address persisting symptom profiles and restore pre-COVID quality of life

Abstract:

Background: Long-COVID diagnosis is prominent, and our attention must support those experiencing debilitating and long-standing symptoms. To establish patient pathways, we must consider the societal and economic impacts of sustained COVID-19. Accordingly, we sought to determine the pertinent areas impacting quality of life (QoL) following a COVID-19 infection.

Research methods: Three hundred and eighty-one participants completed a web-based survey (83% female, 17% male) consisting of 70 questions across 7 sections (demographics, COVID-19 symptoms; QoL; sleep quality; breathlessness; physical activity and mental health). Mean age, height, body mass and body mass index (BMI) were 42 ± 12 years, 167.6 ± 10.4 cm, 81.2 ± 22.2 kg, and 29.1 ± 8.4 kg.m2, respectively.

Results: Participant health was reduced because of COVID-19 symptoms (‘Good health‘ to ‘Poor health‘ [P < 0.001]). Survey respondents who work reported ongoing issues with performing moderate (83%) and vigorous (79%) work-related activities.

Conclusions: COVID-19 patients report reduced capacity to participate in activities associated with daily life, including employment activities. Bespoke COVID-19 support pathways must consider multi-disciplinary approaches that address the holistic needs of patients to restore pre-pandemic quality of life and address experienced health and wellbeing challenges.

Plain Language Summary: The long-term impact of long-COVID has a dramatic impact upon daily activities and lifestyle. The development of bespoke support pathways to support patients must address the physical and psychological considerations to adequately restore pre-COVID quality of life and address broader societal and economic implications, especially for those that are of working age.

Source: Faghy MA, Maden-Wilkinson T, Arena R, Copeland RJ, Owen R, Hodgkins H, Willmott A. COVID-19 patients require multi-disciplinary rehabilitation approaches to address persisting symptom profiles and restore pre-COVID quality of life. Expert Rev Respir Med. 2022 Apr 18:1-6. doi: 10.1080/17476348.2022.2063843. Epub ahead of print. PMID: 35385677. https://www.tandfonline.com/doi/full/10.1080/17476348.2022.2063843 (Full text)

Studying severe long COVID to understand post-infectious disorders beyond COVID-19

To the Editor — As the COVID Human Genetic Effort consortium (https://www.covidhge.com/), we have studied genetic and immunological determinants of life-threatening COVID-19 pneumonia1, multisystem inflammatory syndrome (MIS-C)2, resistance to SARS-CoV-2 infection3 and ‘COVID toes’4, and here we present our efforts to investigate post-acute COVID-19 syndrome, or ‘long COVID’.

Most people infected with SARS-CoV-2 experience a mild to moderate acute infection, while ~10% develop hypoxemic pneumonia and 3% develop critical illness, which are outcomes associated with older age and male sex. Inborn errors of type I interferon immunity involving the viral sensors TLR7 or TLR3 can explain critical disease in 1–5% of people less than 60 years of age, whereas neutralizing autoantibodies to the type I interferons IFN-α, IFN-β and IFN-ω are seen in 15–20% of people over 70 years of age1, which highlights the importance of type I interferon immunity for protective immunity against acute SARS-CoV-2 infection in the respiratory tract.

Although hypoxemic pneumonia typically occurs 2 weeks after infection, a small fraction of children and young adults develop MIS-C at about 4 weeks after infection. This disorder overlaps Kawasaki disease and superantigen-mediated toxic shock syndrome. Immunological analyses have revealed hyperinflammatory immune responses, distinct from those of acute COVID-19 and Kawasaki disease5, and activation of T cells, possibly by a SARS-CoV-2 superantigen6. There is massive expansion of T cells expressing the T cell receptor (TCR) β-chain variable region TRBV11-2 in combination with variable TCR α-chains and broadly reactive autoantibodies2. Intriguingly, the delayed presentation of MIS-C after infection is at odds with other superantigen-mediated disorders, which might be explained by viral persistence specifically in the intestine and repeated superantigen-mediated activation through a leaky gut. Viral persistence has been proposed to be associated with the degree of activation of the immune system during acute infection with SARS-CoV-27.

Signs and symptoms after SARS-CoV-2 infection have been reported to also persist even longer in some children and adults. The World Health Organization defines the ‘post COVID’ condition as one that “occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis” (https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1). Long COVID spans from very mild to severely debilitating disease with objective organ damage, but sometimes the distinction between recovery from post–intensive care unit syndrome and ongoing pathology is not clearly defined or reported in studies.

Interestingly, an acute multi-organ phenotype encompassing multiple neurological, neuropsychological–neurocognitive, cardiopulmonary, gastrointestinal and dermatological complaints during acute COVID-19 correlates with longer persistence of signs and symptoms8.

The World Health Organization’s definition of long COVID is vague, which leads to concerns that a variety of conditions, including psychosomatic complaints, become intermixed with more severe, post-infectious organ dysfunction. To maximize our chances of identifying the human genetic immunological determinants of disease, we will focus our efforts on the most severe cases of long COVID available through our international network of collaborators and clinics. We will include patients with over 3 months of persistent signs and symptoms after PCR-verified SARS-CoV-2 infection. We will also limit our studies to patients with severe organ damage or dysfunction that can be objectively verified by imaging and physiological or biochemical–molecular tests (Fig. 1a). Finally, to distinguish these patients with severe long COVID from patients with post–critical illness syndromes, we will include only patients whose persistent organ dysfunction cannot be explained by the severity of the preceding SARS-CoV-2 infection or by the treatments or medical interventions experienced.

Read the rest of this article HERE.

Source: Brodin P, Casari G, Townsend L, O’Farrelly C, Tancevski I, Löffler-Ragg J, Mogensen TH, Casanova JL; COVID Human Genetic Effort. Studying severe long COVID to understand post-infectious disorders beyond COVID-19. Nat Med. 2022 Apr 5. doi: 10.1038/s41591-022-01766-7. Epub ahead of print. PMID: 35383311. https://www.nature.com/articles/s41591-022-01766-7 (Full article)

COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study

Abstract:

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID – the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID.

The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits.

In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on “objective” cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.

Source: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG. COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study. Front Aging Neurosci. 2022 Mar 17;14:804937. doi: 10.3389/fnagi.2022.804937. PMID: 35370620; PMCID: PMC8967943. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967943/ (Full study)

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study

Abstract:

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere.

There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing “Long COVID”-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not.

We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.

Source: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG. COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study. Front Aging Neurosci. 2022 Mar 17;14:804922. doi: 10.3389/fnagi.2022.804922. PMID: 35370617; PMCID: PMC8968323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968323/ (Full text)

Histopathology of Persistent Long COVID Toe: A Case Report

Abstract:

During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including: pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within ten days of exposure. Biopsy of the distal toe 16 weeks after initial exposure demonstrated papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy of “long COVID toe” following presumed SARS-Cov-2 exposure, with demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.

Source: Nirenberg MS, Requena L, Santonja C, Smith GT, McClain SA. Histopathology of Persistent Long COVID Toe: A Case Report. J Cutan Pathol. 2022 Apr 2. doi: 10.1111/cup.14240. Epub ahead of print. PMID: 35366017.  https://pubmed.ncbi.nlm.nih.gov/35366017/

Persisting olfactory dysfunction in post-COVID-19 is associated with gustatory impairment: Results from chemosensitive testing eight months after the acute infection

Abstract:

Olfactory and gustatory disorders are prominent symptoms of acute COVID-19. Although both senses recover in many patients within weeks to months, persistency has been described in up to 60%. However up to now most reports on the course of chemosensitive disorders after COVID-19 are not based on psychophysical testing but only on subjective patients’ ratings. In this study we assessed both olfaction and gustation using psychophysical tests eight months after COVID-19. Validated psychophysical testing revealed hyposmia in 18% and hypogeusia in even 32% of 303 included patients. This shows that olfactory and especially gustatory disorders have to be seen as important chronic symptoms post-COVID-19. The high prevalence of gustatory dysfunction indicates that gustatory function does not recover or might even deteriorate in the months following the acute infection.

Source: Hintschich CA, Fischer R, Hummel T, Wenzel JJ, Bohr C, Vielsmeier V. Persisting olfactory dysfunction in post-COVID-19 is associated with gustatory impairment: Results from chemosensitive testing eight months after the acute infection. PLoS One. 2022 Mar 23;17(3):e0265686. doi: 10.1371/journal.pone.0265686. PMID: 35320821; PMCID: PMC8942205. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942205/ (Full text)