Tag: long covid symptoms

Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection

Abstract:

Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection.

Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS.

Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers.

The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers.

Source: Kirchberger I, Meisinger C, Warm TD, Hyhlik-Dürr A, Linseisen J, Goßlau Y. Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection. Viruses. 2023 Jun 5;15(6):1326. doi: 10.3390/v15061326. PMID: 37376625; PMCID: PMC10303962. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303962/ (Full text)

Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation

Abstract:

Background: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term.

Methodology: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization.

Results: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (>3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis.

Conclusion: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Source: Bhattacharyya P, Sengupta S, De A, Mukherjee S, Paul M, Dey D. Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation. J Assoc Physicians India. 2022 Nov;70(11):11-12. doi: 10.5005/japi-11001-0147. PMID: 37355939. https://japi.org/article/files/JAPI0147_p18-22_compressed.pdf (Full text)

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up

Abstract:

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry.

In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization.

The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Source: Babicki M, Kapusta J, Pieniawska-Śmiech K, Kałuzińska-Kołat Ż, Kołat D, Mastalerz-Migas A, Jankowski P, Chudzik M. Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up. Viruses. 2023 Jun 13;15(6):1370. doi: 10.3390/v15061370. PMID: 37376668; PMCID: PMC10304551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304551/ (Full text)

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

Abstract:

Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration.

Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models.

Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral-microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.

Source: Zhang J, Zhang Y, Xia Y, Sun J. Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19. Genes Dis. 2023 Jun 19. doi: 10.1016/j.gendis.2023.03.034. Epub ahead of print. PMID: 37362775; PMCID: PMC10278891. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278891/ (Full text)

Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis

Abstract:

Long-term persistent symptoms of COVID-19 affect 30-80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities.

The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286).

Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model.

The results showed an overall medium-high effect size (g = -.68, p = .02) with a 95% CI (-1.05 to -.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls.

Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear.

Source: Sobrino-Relaño S, Balboa-Bandeira Y, Peña J, Ibarretxe-Bilbao N, Zubiaurre-Elorza L, Ojeda N. Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis. Sci Rep. 2023 Jun 26;13(1):10309. doi: 10.1038/s41598-023-37420-6. PMID: 37365191; PMCID: PMC10293265. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293265/ (Full text)

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)

Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy

Background: The negative impact of long COVID on social life and human health is increasingly prominent, and the elevated risk of cardiovascular disease in patients recovering from COVID-19 has also been fully confirmed. However, the pathogenesis of long COVID-related inflammatory cardiomyopathy is still unclear. Here, we explore potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy.

Methods: Datasets that met the study requirements were identified in Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were obtained by the algorithm. Then, functional enrichment analysis was performed to explore the basic molecular mechanisms and biological processes associated with DEGs. A protein–protein interaction (PPI) network was constructed and analyzed to identify hub genes among the common DEGs. Finally, a third dataset was introduced for validation.

Results: Ultimately, 3,098 upregulated DEGs and 1965 downregulated DEGs were extracted from the inflammatory cardiomyopathy dataset. A total of 89 upregulated DEGs and 217 downregulated DEGs were extracted from the dataset of convalescent COVID patients. Enrichment analysis and construction of the PPI network confirmed VEGFA, FOXO1, CXCR4, and SMAD4 as upregulated hub genes and KRAS and TXN as downregulated hub genes. The separate dataset of patients with COVID-19 infection used for verification led to speculation that long COVID-associated inflammatory cardiomyopathy is mainly attributable to the immune-mediated response and inflammation rather than to direct infection of cells by the virus.

Conclusion: Screening of potential biomarkers and therapeutic targets sheds new light on the pathogenesis of long COVID-associated inflammatory cardiomyopathy as well as potential therapeutic approaches. Further clinical studies are needed to explore these possibilities in light of the increasingly severe negative impacts of long COVID.

Source: Peng Qi, Mengjie Huang and Haiyan Zhu. Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy. Front. Med., 29 June 2023. Sec. Infectious Diseases: Pathogenesis and Therapy. Volume 10 – 2023 | https://doi.org/10.3389/fmed.2023.1191354 https://www.frontiersin.org/articles/10.3389/fmed.2023.1191354/full (Full text)

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Abstract:

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized.

Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases.

Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis.

Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk.

Trial Registration NCT04549831 (www.clinicaltrial.org)

Source: Bergantini, L., Baldassarri, M., d’Alessandro, M. et al. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder. Respir Res 24, 158 (2023). https://doi.org/10.1186/s12931-023-02458-7 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02458-7 (Full text)

Natural history of long-COVID

Abstract:

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test.

Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.

Source: Hastie, C.E., Lowe, D.J., McAuley, A. et al. Natural history of long-COVID in a nationwide, population cohort study. Nat Commun 14, 3504 (2023). https://doi.org/10.1038/s41467-023-39193-y https://www.nature.com/articles/s41467-023-39193-y (Full text)

Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months

Abstract:

COVID-19 causes immune perturbations which may persist long-term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate or severe disease and investigated whether it associates with long COVID.

At 3 months, patients with severe disease displayed persistent activation of CD4+ and CD8+ T-cells, based on expression of HLA-DR, CD38, Ki67 and granzyme B, and elevated plasma levels of IL-4, IL-7, IL-17 and TNF-α compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation.

Patients with severe disease reported a higher number of long COVID symptoms which did not however, correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex and disease severity. Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.

Source: Marianna Santopaolo, Michaela Gregorova, Fergus Hamilton, David Arnold, Anna Long, Aurora Lacey, Alice Halliday, Holly Baum, Kristy Hamilton, Rachel Milligan, Elizabeth Oliver, Olivia Pearce, Lea Knezevic, Begonia Morales Aza, Alice Milne, Emily Milodowski, Eben Jones, Rajeka Lazarus, Anu Goenka, Adam Finn, Nicholas Maskell, Andrew D Davidson, Kathleen Gillespie, Linda Wooldridge, Laura Rivino (2023) Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months eLife 12:e85009 https://doi.org/10.7554/eLife.85009 https://elifesciences.org/articles/85009