Tag: mild covid

Brain temperature and free water increases after mild COVID-19 infection

Abstract:

The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild infection. Chronic neuroinflammation may underlie these enduring symptoms, but studying neuroinflammatory phenomena in vivo is challenging, especially without a comparable pre-COVID-19 dataset.

In this study, we present a unique dataset of 10 otherwise healthy individuals scanned before and after experiencing mild COVID-19. Two emerging MR-based methods were used to map pre- to post-COVID-19 brain temperature and free water changes. Post-COVID-19 brain temperature and free water increases, which are indirect biomarkers of neuroinflammation, were found in structures functionally associated with olfactory, cognitive, and memory processing.

The largest pre- to post-COVID brain temperature increase was observed in the left olfactory tubercle (p = 0.007, 95% CI [0.48, 3.01]), with a mean increase of 1.75 °C. Notably, the olfactory tubercle is also the region of the primary olfactory cortex where participants with chronic olfactory dysfunction showed the most pronounced increases as compared to those without lingering olfactory dysfunction (adjusted pFDR = 0.0189, 95% CI [1.42, 5.27]). These preliminary insights suggest a potential link between neuroinflammation and chronic cognitive and olfactory dysfunction following mild COVID-19, although further investigations are needed to improve our understanding of what underlies these phenomena.

Source: Sharma AA, Nenert R, Goodman AM, Szaflarski JP. Brain temperature and free water increases after mild COVID-19 infection. Sci Rep. 2024 Mar 28;14(1):7450. doi: 10.1038/s41598-024-57561-6. PMID: 38548815; PMCID: PMC10978935. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978935/ (Full text)

Role of the complement system in Long COVID

Abstract:

Long COVID, or Post-Acute COVID Syndrome (PACS), may develop following SARS-CoV-2 infection, posing a substantial burden to society. Recently, PACS has been linked to a persistent activation of the complement system (CS), offering hope for both a diagnostic tool and targeted therapy. However, our findings indicate that, after adjusting proteomics data for age, body mass index and sex imbalances, the evidence of complement system activation disappears.

Furthermore, proteomic analysis of two orthogonal cohorts—one addressing PACS following severe acute phase and another after a mild acute phase—fails to support the notion of persistent CS activation. Instead, we identify a proteomic signature indicative of either ongoing infections or sustained immune activation similar to that observed in acute COVID-19, particularly within the mild-PACS cohort.

Source: Vadim Farztdinov, Boris Zühlke, Franziska Sotzny, Fridolin Steinbeis, Martina Seifert, Claudia Kedor, Kirsten Wittke, Pinkus Tober-Lau, Thomas Zoller, Kathrin Textoris-Taube, Daniela Ludwig, Clemens Dierks, Dominik Bierbaum, Leif Erik Sander, Leif G Hanitsch, Martin Witzenrath, Florian Kurth, Michael Mülleder, Carmen Scheibenbogen, Markus Ralser. Role of the complement system in Long COVID. medRxiv 2024.03.14.24304224; doi: https://doi.org/10.1101/2024.03.14.24304224 https://www.medrxiv.org/content/10.1101/2024.03.14.24304224v1.full-text (Full text)

Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection

Abstract:

Background: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19.

Methods: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL.

Results: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (β=-0.080, p = 0.001) and long COVID (β=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (β=-0.147, p = 0.026) and long (β=-0.186, p < 0.001) COVID.

Conclusion: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.

Source: Soare IA, Ansari W, Nguyen JL, Mendes D, Ahmed W, Atkinson J, Scott A, Atwell JE, Longworth L, Becker F. Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection. Health Qual Life Outcomes. 2024 Jan 30;22(1):12. doi: 10.1186/s12955-024-02230-5. PMID: 38287294; PMCID: PMC10826014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826014/ (Full text)

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

Abstract:

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals.

We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI).

The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls.

Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI).

Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Source: Scardua-Silva, L., Amorim da Costa, B., Karmann Aventurato, Í. et al. Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19. Sci Rep 14, 1758 (2024). https://doi.org/10.1038/s41598-024-52005-7  https://www.nature.com/articles/s41598-024-52005-7 (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)

The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study

Abstract:

Background: SARS-CoV-2 may affect the male reproductive system as it uses angiotensin-converting enzyme [ACE]2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild COVID-19 on testicular function, and INSL3 levels have not previously been assessed during acute SARS-CoV-2 infection.

Objectives: To assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19.

Materials and methods: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 RT-PCR test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters.

Results: Lower plasma testosterone [T] (total and calculated free [c-fT]) and higher LH concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (P < 0.001 and P = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (P = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (P = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point.

Discussion and conclusion: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded. This article is protected by copyright. All rights reserved.

Source: Lauritsen MP, Kristensen TL, Bo Hansen C, Schneider UV, Talbot AL, Skytte AB, Petersen JH, Johannsen TH, Zedeler A, Albrethsen J, Juul A, Priskorn L, Jørgensen N, Westh H, Freiesleben NC, Nielsen HS. The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study. Andrology. 2023 Jul 8. doi: 10.1111/andr.13494. Epub ahead of print. PMID: 37421657. https://pubmed.ncbi.nlm.nih.gov/37421657/

Mild COVID-19 infection associated with post-COVID-19 condition after 3 months – a questionnaire survey

Abstract:

Introduction: The coronavirus disease 2019 (COVID-19), caused by infection with SARS-CoV-2, can lead to post-COVID-19 condition, a secondary syndrome of persistent and new post-acute symptoms, but evidence on this syndrome is still scarce.

Methods: In a questionnaire survey, residents of the city of Bremen (Germany) with verified SARS-CoV-2 infection were invited to answer questions (online questionnaire or interview) concerning symptoms experienced at the time of infection and at the time of questionnaire completion at least three months later. Main outcome of the analysis was the presence of a post-COVID-19 condition at the time of the interview, defined as the presence of at least two of three leading symptoms: fatigue, breathing difficulties, or cognitive problems.

Results: A post-COVID-19 condition was more likely to be reported if respondents had, at the time of infection, suffered from fatigue (OR 1.75; 95% CI: 1.00, 3.06), breathing difficulties (OR 4.02; 95% CI: 2.80, 5.77), cognitive symptoms (OR 2.98; 95% CI: 1.48, 6.02), or head- & bone aches (OR 2.06; 95% CI: 1.25, 3.42). The odds of developing a post-COVID-19 condition increased with the number of symptoms at infection. Females were more likely to report a post-COVID-19 condition (OR 1.54; 95% CI: 1.05, 2.24). Analyzing only non-hospitalized respondents changed results only slightly.

Conclusion: Our study adds to growing evidence that even a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition. Females and those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to also experience post COVID-19 symptoms several months after infection.

KEY MESSAGES

Even a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition.

Females seem more likely to develop a post-COVID-19 condition.

Those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to develop a post-COVID-19 condition.

Source: Rach S, Kühne L, Zeeb H, Ahrens W, Haug U, Pohlabeln H. Mild COVID-19 infection associated with post-COVID-19 condition after 3 months – a questionnaire survey. Ann Med. 2023 Dec;55(1):2226907. doi: 10.1080/07853890.2023.2226907. PMID: 37337723; PMCID: PMC10283437. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283437/ (Full text)

Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection

Abstract:

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children.

This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time.

Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. ‘

Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.

Source: Eder J, Schumm L, Armann JP, Puhan MA, Beuschlein F, Kirschbaum C, Berner R, Toepfner N. Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection. Sci Rep. 2023 Jun 17;13(1):9823. doi: 10.1038/s41598-023-35692-6. PMID: 37330522. https://www.nature.com/articles/s41598-023-35692-6 (Full text)

Long COVID syndrome after SARS-CoV-2 survival in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Abstract:

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients have a more severe COVID-19 course than the general population. Many patients report different persistent symptoms after SARS-CoV-2 infection. The aim of our study is to analyze the prevalence of long COVID-19 symptoms and assess if COVID-19 affects pulmonary hypertension (PH) prognosis.

PAH/CTEPH patients who survived COVID-19 for at least 3 months before visiting the PH centers were included in the study. The patients were assessed for symptoms in acute phase of SARS-CoV-2 infection and persisting in follow-up visit, WHO functional class, 6-min walk distance, NT-proBNP concentration. The COMPERA 2.0 model was used to calculate 1-year risk of death due to PH at baseline and at follow-up. Sixty-nine patients-54 (77.3%) with PAH and 15 (21.7%) with CTEPH, 68% women, with a median age of 47.5 years (IQR 37-68)-were enrolled in the study.

About 17.1% of patients were hospitalized due to COVID-19 but none in an ICU. At follow-up (median: 155 days after onset of SARS-CoV-2 symptoms), 62% of patients reported at least 1 COVID-19-related symptom and 20% at least 5 symptoms. The most frequently reported symptoms were: fatigue (30%), joint pain (23%), muscle pain (17%), nasal congestion (17%), anosmia (13%), insomnia (13%), and dyspnea (12%).

Seventy-two percent of PH patients had a low or intermediate-low risk of 1-year death due to PH at baseline, and 68% after COVID-19 at follow-up. Over 60% of PAH/CTEPH patients who survived COVID-19 suffered from long COVID-19 syndrome, but the calculated 1-year risk of death due to PH did not change significantly after surviving mild or moderate COVID-19.

Source: Wieteska-Miłek M, Kuśmierczyk-Droszcz B, Betkier-Lipińska K, Szmit S, Florczyk M, Zieliński P, Hoffman P, Krzesińki P, Kurzyna M. Long COVID syndrome after SARS-CoV-2 survival in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Pulm Circ. 2023 May 31;13(2):e12244. doi: 10.1002/pul2.12244. PMID: 37266140; PMCID: PMC10232226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232226/ (Full text)