Tag: long covid symptoms

Postacute sequelae of COVID-19 at 2 years

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection.

The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively.

Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6-89.6) and 642.8 (95% CI: 596.9-689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9-31.0%) and 21.3% (18.2-24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year.

In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.

Source: Bowe B, Xie Y, Al-Aly Z. Postacute sequelae of COVID-19 at 2 years. Nat Med. 2023 Aug 21. doi: 10.1038/s41591-023-02521-2. Epub ahead of print. PMID: 37605079. https://www.nature.com/articles/s41591-023-02521-2 (Full text)

Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19

Abstract:

The coronavirus disease 2019 (COVID-19) remains an epidemic worldwide. Most patients suffer residual symptoms, the so-called “Long COVID,” which includes respiratory and neuropsychiatric symptoms. Brain Fog, one of the symptoms of Long COVID, is a major public health issue because it can impair patients’ quality of life even after recovery from the disease. However, neither the pathogenesis nor the treatment of this condition remains unknown.

We focused on serum ferritin levels in this study and collected information on the onset of Brain Fog through questionnaires and found that high ferritin levels during hospitalization were associated with the occurrence of Brain Fog. In addition, we excluded confounders as far as possible using propensity score analyses and found that ferritin was independently associated with Brain Fog in most of the models. We conducted phase analysis and evaluated the interaction of each phase with ferritin levels and Brain Fog.

We found a positive correlation between serum ferritin levels during hospitalization and Brain Fog after COVID-19. High ferritin levels in patients with Brain Fog may reflect the contribution of chronic inflammation in the development of Brain Fog. This study provides a novel insight into the pathogenic mechanism of Brain Fog after COVID-19.

Source: Ishikura T, Nakano T, Kitano T, Tokuda T, Sumi-Akamaru H, Naka T. Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19. Sci Rep. 2023 Aug 11;13(1):13095. doi: 10.1038/s41598-023-40011-0. PMID: 37567939; PMCID: PMC10421912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421912/ (Full text)

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study

Abstract:

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed.

A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening.

A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

Source: Reuken PA, Besteher B, Finke K, Fischer A, Holl A, Katzer K, Lehmann-Pohl K, Lemhöfer C, Nowka M, Puta C, Walter M, Weißenborn C, Stallmach A. Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study. Eur Arch Psychiatry Clin Neurosci. 2023 Aug 16. doi: 10.1007/s00406-023-01661-3. Epub ahead of print. PMID: 37587244. https://link.springer.com/article/10.1007/s00406-023-01661-3 (Full text)

Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022

Abstract:

Objective To characterise Long COVID in a highly vaccinated population infected by Omicron.

Design Follow-up survey of persons testing positive for SARS-CoV-2 in Western Australia, 16 July-3 August 2022.

Setting Community

Participants 22,744 persons with COVID-19 who had agreed to participate in research at the time of diagnosis were texted a survey link 90 days later; non-responders were telephoned. Post stratification weights were applied to responses from 11,697 (51.4%) participants, 94.0% of whom had received >= 3 vaccine doses.

Main outcome measures Prevalence of ‘Long COVID’ – defined as reporting new or ongoing COVID-19 illness-related symptoms or health issues 90 days post diagnosis; associated health care utilisation, reductions in work/study and risk factors were assessed using log-binomial regression.

Results 18.2% (n=2,130) of respondents met case definition for Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%); 38.2% consulted a GP and 1.6% reported hospitalisation in the month prior to the survey due to ongoing symptoms. Of 1,778 respondents with Long COVID who were working/studying before their COVID-19 diagnosis, 17.9% reported reducing/discontinuing work/study.

Conclusion 90 days post Omicron infection, almost 1 in 5 respondents reported Long COVID symptoms; 1 in 15 of all persons with COVID-19 sought healthcare for associated health concerns >=2 months after the acute illness.

The known The prevalence of Long COVID varies widely across studies conducted in diverse settings globally (range: 9%-81%).

The new In a highly vaccinated population (94% with >=3 vaccine doses), almost 20% of persons infected with the SARS-CoV-2 Omicron variant reported symptoms consistent with Long COVID 90 days post diagnosis. Long COVID was associated with sustained negative impacts on work/study and a substantial utilisation of GP services 2-3 months after the acute illness; however, ED presentations and hospitalisations for Long COVID were rare.

The implications GP clinics play a significant role in managing the burden of Long COVID in Australia.

Source: Mulu Woldegiorgis, Gemma Cadby, Sera Ngeh, Rosemary Korda, Paul Armstrong, Jelena Maticevic, Paul Knight, Andrew Jardine, Lauren Bloomfield, Paul Effler. Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022. medRxiv 2023.08.06.23293706; doi: https://doi.org/10.1101/2023.08.06.23293706 https://www.medrxiv.org/content/10.1101/2023.08.06.23293706v1.full-text (Full text)

Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study

Abstract:

Objectives: Ongoing symptomatic coronavirus disease 2019 (OSC) is defined as persistent symptoms beyond 4 weeks of acute illness. OSC leads to prolonged hospitalization and oxygen dependence. We aimed to find the outcome of Janus kinase inhibitors (JAKi) as a steroid-sparing agent to treat OSC.

Methods: In this single-center case-controlled study comparing JAKi and corticosteroids in OSC cases, data of 41 cases out of 86 were included – 21 in the JAKi group and 20 in the corticosteroid group from 4 weeks of acute illness to the next 4 weeks. Clinical parameters and inflammatory markers were recorded. The primary outcome was to compare the proportion of patients who were able to maintain oxygen saturation ≥95% with any oxygen supplementation in the two groups.

Results: The baseline clinical and demographic characteristics were similar in the two groups. The age was 53.65 ± 9.8 years and 51.48 ± 14.0 years in the corticosteroid group and JAKi group, respectively. At the baseline, 85% of patients in the corticosteroid group and 85.8% in the JAKi group were on oxygen support. The most common symptom in both groups was breathlessness followed by cough. Twenty percent of patients in the JAKi group received baricitinib and the remaining were given tofacitinib. At the time of follow-up, the majority of cases had a significant reduction in C-reactive protein (CRP) and D-dimer; however, the change in CRP and D-dimer was similar in both groups. The number of patients off oxygen support at 4 weeks was higher in the JAKi group (85% in the corticosteroid group vs. 95.2% in the JAKi group, P = 0.269), and the median time to liberation from oxygen support was significantly lower in JAKi group (19 days in corticosteroid group vs. 9 days in JAKi group, P < 0.001). The frequency of any adverse event was also higher in the corticosteroid group (70% vs. 23.8%, P = 0.003).

Conclusion: JAKi can be used as immunomodulatory drugs in hypoxic OSC cases having evidence of ongoing inflammation.

Source: Singh PK, Sharma VK, Lalwani LK, Chaudhry D, Govindagoudar MB, Sriram CP, Ahuja A. Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study. Turk J Emerg Med. 2023 Jun 26;23(3):149-155. doi: 10.4103/tjem.tjem_363_22. PMID: 37529783; PMCID: PMC10389097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10389097/ (Full text)

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC)

Abstract:

Background: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce.

Methods: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests and physical examination were obtained from all patients. SARSCoV-2 reactive T cell response was analyzed via multiparametric flowcytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay.

Results: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells.

Conclusions: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.

Source: Krystallenia Paniskaki, et al. Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC) https://d197for5662m48.cloudfront.net/documents/publicationstatus/144335/preprint_pdf/a855de5e766f9457795050e56413075a.pdf (Full text)

Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects

Abstract:

In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022.

Amino acids and metabolites were measured by gas chromatography–mass spectrometry (GC–MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326).

The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = − 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003).

Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

Source: Mikuteit, M., Baskal, S., Klawitter, S. et al. Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects. Amino Acids (2023). https://doi.org/10.1007/s00726-023-03305-1 https://link.springer.com/article/10.1007/s00726-023-03305-1 (Full text)

A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework

Abstract:

Physical and psychological symptoms lasting months following an acute COVID-19 infection are now recognized as post-acute sequelae of COVID-19 (PASC). Accurate tools for identifying such patients could enhance screening capabilities for the recruitment for clinical trials, improve the reliability of disease estimates, and allow for more accurate downstream cohort analysis.

In this retrospective cohort study, we analyzed the EHR of hospitalized COVID-19 patients across three healthcare systems to develop a pipeline for better identifying patients with persistent PASC symptoms (dyspnea, fatigue, or joint pain) after their SARS-CoV-2 infection. We implemented distributed representation learning powered by the Machine Learning for modeling Health Outcomes (MLHO) to identify novel EHR features that could suggest PASC symptoms outside of typical diagnosis codes. MLHO applies an entropy-based feature selection and boosting algorithms for representation mining. These improved definitions were then used for estimating PASC among hospitalized patients.

30,422 hospitalized patients were diagnosed with COVID-19 across three healthcare systems between March 13, 2020 and February 28, 2021. The mean age of the population was 62.3 years (SD, 21.0 years) and 15,124 (49.7%) were female.

We implemented the distributed representation learning technique to augment PASC definitions. These definitions were found to have positive predictive values of 0.73, 0.74, and 0.91 for dyspnea, fatigue, and joint pain, respectively.

We estimated that 25 percent (CI 95%: 6-48), 11 percent (CI 95%: 6-15), and 13 percent (CI 95%: 8-17) of hospitalized COVID-19 patients will have dyspnea, fatigue, and joint pain, respectively, 3 months or longer after a COVID-19 diagnosis. We present a validated framework for screening and identifying patients with PASC in the EHR and then use the tool to estimate its prevalence among hospitalized COVID-19 patients.

Source: Strasser ZH, Dagliati A, Shakeri Hossein Abad Z, Klann JG, Wagholikar KB, Mesa R, Visweswaran S, Morris M, Luo Y, Henderson DW, Samayamuthu MJ; Consortium for Clinical Characterization of COVID-19 by EHR (4CE); Omenn GS, Xia Z, Holmes JH, Estiri H, Murphy SN. A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework. PLOS Digit Health. 2023 Jul 25;2(7):e0000301. doi: 10.1371/journal.pdig.0000301. PMID: 37490472; PMCID: PMC10368277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368277/ (Full text)

First insights from patients presenting with long/post-COVID syndrome in primary care: an exploratory report

Abstract:

Background: Following the global pandemic of coronavirus disease 2019 (COVID-19), the long COVID or post-COVID syndrome refers to a relatively complex novel clinical entity. We conducted this study to assess the primary epidemiological features, main symptoms, and comorbidities probably related to this syndrome in patients referred to our long/post-COVID primary care unit during the initial months of its operation.

Methods and material: This single-center prospective observational study was conducted between April 2022 and December 2022 and enrolled 71 patients (33 men, 38 women) who were examined due to persisting symptoms after recovering from COVID-19 infection, with the mean time of the first visit estimated at 3.12 ± 2.41 months from their acute COVID-19 illness. A thorough medical history, clinical examination, laboratory, and any other tests were performed on all patients when necessary.

Results: The most common symptoms of long/post-COVID reported were fatigue (63.4 %), a persistent cough (45.1 %), stress manifestations (42.3 %), arthralgia or myalgia (33.8 %), tachycardia (32.4 %), depression manifestations (29.6 %), exertional dyspnea (28.2 %), and sleep disorders (25.4 %). Hypertension (in about 40 %) and the presence of five or more symptoms during the acute COVID-19 illness (in approximately 52 %) could be regarded as factors increasing the long/post-COVID appearance. The long/post-COVID syndrome affects even patients not experiencing severe COVID-19 illness. Unvaccinated patients are at higher risk of severe COVID-19 (p =0.014), higher risk of hospitalization (p =0.002), and in higher need of respiratory support with high flow (p =0.017) when compared to vaccinated ones. Hospitalized patients appear to be older than outpatients (59 ± 12.42 vs 52.78 ± 11.48 years of age; p =0.032.

Conclusion: The long/post-COVID syndrome is an established clinical entity, and several clinical features, symptoms, and patient profiles have to be assessed from the initial medical contact in primary care to exclude early any other clinical conditions and offer guided therapeutic strategies to those patients. HIPPOKRATIA 2022, 26 (4):138-142.

Source: Sotiriadou M, Birka S, Oikonomidou E, Κouzoukidou E, Mpogiatzidis P. First insights from patients presenting with long/post-COVID syndrome in primary care: an exploratory report. Hippokratia. 2022 Oct-Dec;26(4):138-142. PMID: 37497527; PMCID: PMC10367945. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10367945/ (Full text)

Initial COVID-19 Severity and Long-COVID Manifestations: An Observational Analysis

Abstract:

Objective: New-onset or persistent symptoms beyond after 4 weeks from COVID-19 are termed “long-COVID.” Whether the initial severity of COVID-19 has a bearing on the clinicoradiological manifestations of long COVID is an area of interest.

Material and methods: We did an observational analysis of the long-COVID patients after categorizing them based on their course of COVID-19 illness into mild, moderate, and severe groups. The clinical and radiological profile was compared across these groups.

Results: Out of 150 long-COVID patients recruited in the study, about 79% (118), 14% (22), and 7% (10) had a history of mild, moderate, and severe COVID-19, respectively. Fatigue (P = .001), breathlessness (P = .001), tachycardia (P = .002), tachypnea (P < .001), raised blood pressure (P < .001), crepitations (P = .04), hypoxia at rest (P < .001), significant desaturation in 6-minute walk test (P = .27), type 1 respiratory failure (P = .001), and type 2 respiratory failure (P = .001) were found to be significantly higher in the long-COVID patients with a history of severe COVID-19. These patients also had the highest prevalence of abnormal chest X-ray (60%) and honeycombing in computed tomography scan thorax (25%, P = .027).

Conclusion: The course of long COVID bears a relationship with initial COVID-19 severity. Patients with severe COVID-19 are prone to develop more serious long-COVID manifestations.

Source: Goel N, Goyal N, Spalgais S, Mrigpuri P, Varma-Basil M, Khanna M, Nagaraja R, Menon B, Kumar R. Initial COVID-19 Severity and Long-COVID Manifestations: An Observational Analysis. Thorac Res Pract. 2023 Jan;24(1):22-28. doi: 10.5152/ThoracResPract.2023.21307. PMID: 37503595. https://thoracrespract.org/en/initial-covid-19-severity-and-long-covid-manifestations-an-observational-analysis-165530 (Full text as PDF file)