Tag: long covid symptoms
Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review
Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID’s impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation.
Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.
These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.
We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.
Source: Pollack Beth, von Saltza Emelia, McCorkell Lisa, Santos Lucia, Hultman Ashley, Cohen Alison K., Soares Letícia. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Frontiers in Rehabilitation Sciences, Vol 4, 2023, ISSN=2673-6861. DOI: 10.3389/fresc.2023.1122673 https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673 (Full text)
Lung diffusing capacities for nitric oxide and carbon monoxide at rest and post-walking in long COVID
Abstract:
Background: Approximately one-third of long coronavirus disease 2019 (long COVID) patients report breathlessness and fatigue even during activities of daily living. We hypothesised that abnormalities of combined diffusing capacity of the lung for nitric oxide (D LNO) and carbon monoxide (D LCO) at rest or after mild exercise are associated with breathlessness in patients with long COVID.
Methods: Single-breath combined D LNO and D LCO were measured at rest and immediately after a short bout of treadmill exercise simulating ordinary walking in 32 Caucasian patients with long COVID and dyspnoea at rest. 20 subjects served as a control group.
Results: At rest, combined D LNO, D LCO and alveolar volume (V A) were significantly lower in long COVID than in controls, with D LNO and D LCO being below the limits of normal in 69% and 41% of cases, respectively. Mean values of D LNO/V A and D LCO/V A in long COVID patients were less than controls, yet, in only 22% and 12% of long COVID patients were the values of D LNO/V A and D LCO/V A below the limits of normal. After treadmill exercise, D LNO, D LNO/D LCO, V A and heart rate increased significantly without differences between groups. D LNO remained below the limit of normal in 47% of long COVID patients.
Conclusion: These data suggest localised discrete loss of lung units in approximately half of long COVID patients, not completely explained by loss of V A or of alveolar-capillary recruitment during exercise.
Source: Barisione G, Brusasco V. Lung diffusing capacities for nitric oxide and carbon monoxide at rest and post-walking in long COVID. ERJ Open Res. 2023 Apr 17;9(2):00363-2022. doi: 10.1183/23120541.00363-2022. PMID: 37070120; PMCID: PMC9638122. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638122/ (Full text)
Chronic Disease Self-Management of Post-Acute Sequelae of COVID-19 Among Older Adults: A Mixed-Methods Analysis
Abstract:
Introduction: Approximately 20-30% of individuals who contract acute coronavirus disease (COVID-19) infection develop longer term complications of their initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). PASC is characterized by chronic, varying symptomatology.
Methods: Using a mixed methods study design, we aimed to gain insight into individuals’ experience with PASC, including cognitive issues, fatigue, and sleep disturbances. We explored whether our previously developed application (app), aimed at improving self-management skills among individuals with chronic diseases, is relevant for individuals with PASC and gained information to adapt the app for individuals with PASC. The study included 19 individuals, aged 40 years and older, recruited from our research participant database, Nova Southeastern University clinics, and community locations. We included this age range because older adults are more likely to have comorbid conditions, allowing us to better understand the impact of COVID-19 infection in these individuals. Participants completed seven standardized self-report questionnaires online, and an individual semi-structured interview via videoconferencing. Quantitative data were assessed using descriptive statistics and calculating individuals’ scores in relation to norms. Qualitative data were analyzed using a thematic analysis approach. Triangulation of the data was accomplished by calculating correlations between participants’ responses on self-report scales and themes found in semi-structured interviews.
Results: Themes included disruption of everyday life, diverse physical symptoms, and cognitive problems including brain fog, fatigue, coping, and emotional upset. Quantitative analysis demonstrated that participants experienced high levels of fatigue, negative mood, cognitive problems, and overall reduction in health-related quality of life (HRQOL). Correlation analyses revealed that individual interview responses were related to participants’ self-report of symptoms on standard questionnaires.
Discussion: Findings indicate that self-report questionnaires may reflect the experience of individuals with PASC and its impact. Additionally, further efforts to expand our prior mobile app are warranted among individuals with PASC.
Source: Thomas-Purcell K, Davenport R, Ayala V, Purcell D, Ownby RL. Chronic Disease Self-Management of Post-Acute Sequelae of COVID-19 Among Older Adults: A Mixed-Methods Analysis. Clin Interv Aging. 2023 Apr 14;18:607-617. doi: 10.2147/CIA.S393732. PMID: 37082741; PMCID: PMC10112475. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112475/
Cytokine deficiencies in patients with Long-COVID
Abstract:
Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of Interferon Gamma (IFNγ) and Interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID.
We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.
Source: Williams ES, Martins TB, Shah KS, Hill HR, Coiras M, Spivak AM, Planelles V. Cytokine Deficiencies in Patients with Long-COVID. J Clin Cell Immunol. 2022;13(6):672. Epub 2022 Nov 18. PMID: 36742994; PMCID: PMC9894377. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894377/ (Full text)
Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort
Abstract:
Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences.
Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria.
Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS.
Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.
Source: Anna Franziska Legler, Lil Meyer-Arndt, Lukas Moedl, Claudia Kedor, Helma Freitag, Elena Steinle, Uta Hoppmann, Rebekka Rust, Frank Konietschke, Andreas Thiel, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl. Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort.
medRxiv 2023.04.15.23288582; doi: https://doi.org/10.1101/2023.04.15.23288582 (Full text available as PDF file)
The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms
Abstract:
Background: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms.
Methods: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes.
Results: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants.
Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses.
Source: Buck AM, Deitchman AN, Takahashi S, Lu S, Goldberg SA, Hoh R, Williams MC, Kerbleski M, Deveau TM, Munter SE, Lombardo J, Wrin T, Petropoulos CJ, Durstenfeld MS, Hsue PY, Kelly JD, Greenhouse B, Martin JN, Deeks SG, Peluso MJ, Henrich TJ. The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms. medRxiv [Preprint]. 2023 Mar 31:2023.03.30.23287923. doi: 10.1101/2023.03.30.23287923. PMID: 37034660; PMCID: PMC10081395. https://www.medrxiv.org/content/10.1101/2023.03.30.23287923v1.full-text (Full text)
Risk factors for psychiatric symptoms in patients with long COVID: A systematic review
Abstract:
Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear.
In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included.
Several limitations in this review were the heterogeneity of studies’ outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.
Source: Zakia H, Pradana K, Iskandar S. Risk factors for psychiatric symptoms in patients with long COVID: A systematic review. PLoS One. 2023 Apr 7;18(4):e0284075. doi: 10.1371/journal.pone.0284075. PMID: 37027455; PMCID: PMC10081737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081737/ (Full text)
Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan
Abstract:
Purpose: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters.
Methods: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal–Wallis test. Multiple comparison tests were performed using the Dunn’s test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals.
Results: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively.
Conclusions: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.
Source: Tsuchida, T., Yoshimura, N., Ishizuka, K. et al. Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan. Clin Exp Med (2023). https://doi.org/10.1007/s10238-023-01057-6 (Full text)
Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative
Abstract:
Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively.
With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients.
We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.
Source: Zang C, Zhang Y, Xu J, Bian J, Morozyuk D, Schenck EJ, Khullar D, Nordvig AS, Shenkman EA, Rothman RL, Block JP, Lyman K, Weiner MG, Carton TW, Wang F, Kaushal R. Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative. Nat Commun. 2023 Apr 7;14(1):1948. doi: 10.1038/s41467-023-37653-z. PMID: 37029117; PMCID: PMC10080528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080528/ (Full text)