Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort

Summary:

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.

Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677.

Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively).

Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials.

Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.

Source: Elisa Gentilotti, Anna Górska, Adriana Tami, Roy Gusinow, Massimo Mirandola, Jesús Rodríguez Baño, et al. Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort. Lancet,  “eClinicalMedicine” https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00284-5/fulltext (Full text)

Exploring the Complexities of Long Covid: An Analysis of Illness Narratives through Antonovsky’s Sense of Coherence Theory

Abstract:

Long Covid is a chronic illness resulting from Covid-19 infection, characterized by persistent symptoms over an extended period. Given the significant impact on affected individuals’ lives, it is crucial to understand and interpret their experiences. Therefore, comprehending how affected individuals understand, manage, and derive meaning from their lives becomes essential.

Antonovsky’s Sense of Coherence (SOC) theory (1987), compromising Comprehensibility, Manageability, and Meaningfulness, can serve as a foundation for this exploration. SOC is shaped by life experiences and aids in finding effective coping strategies. However, the expression of SOC among people with long Covid has not yet been studied. Therefore, this study examines how people with long Covid negotiate the three SOC components in illness narratives.

Thematic analysis of 34 online collected illness narratives from Dutch individuals with long Covid revealed 13 themes interpreted in relation to SOC components. The findings include three themes that were interpreted as reflecting the Comprehensibility component, displaying an understanding of long Covid and its’ impact, and experiences of social support.

Three themes fall under Manageability by describing maintaining control and normality through seeking professional help and adapting to the new state of health. Meaningfulness was characterized by two themes, expressing recognition of values and a sense of direction for maintaining motivation in recovery. Five themes were interpreted as barriers to SOC components, as participants mentioned experiencing misunderstanding and invalidations, medical and public uncertainty, relinquishing enjoyable activities, and struggles in progress and illness acceptance. These results can enhance understanding of long Covid among individuals and assist healthcare practitioners tailor interventions to their specific needs.

Source: Estelle Gosch. Exploring the Complexities of Long Covid: An Analysis of Illness Narratives through Antonovsky’s Sense of Coherence Theory. Master Thesis Positive Clinical Psychology and Technology, Department of Psychology, Health, and Technology, Faculty Behavioural, Management, and Social Sciences, University of Twente. http://essay.utwente.nl/95672/1/Gosch_MA_BMS.pdf (Full text)

Long COVID prevalence and impact on quality of life 2 years after acute COVID-19

Abstract:

There has been an increasing interest in the long-term impact of long COVID. However, only a few studies have investigated the clinical manifestations of long COVID after 24 months of acute infection. In this study, prospective online surveys were conducted in adults previously diagnosed with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13, 2020, at 6, 12, and 24 months after COVID-19.

We investigated self-reported symptoms and the EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys. After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis. Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%), insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the incidence of long COVID at 24 months in terms of the number of vaccinations received.

Although the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants. Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time, and COVID-19 vaccination or the number of vaccinations received may not significantly affect the incidence of long COVID.

Source: Kim Y, Bae S, Chang HH, Kim SW. Long COVID prevalence and impact on quality of life 2 years after acute COVID-19. Sci Rep. 2023 Jul 11;13(1):11207. doi: 10.1038/s41598-023-36995-4. PMID: 37433819. https://www.nature.com/articles/s41598-023-36995-4 (Full text)

High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning

Abstract:

Background: Autonomic dysfunction including postural orthostatic tachycardia syndrome (POTS) has been reported in individuals with post-acute sequelae of Covid-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls.

Methods: All participants were prospectively enrolled between 5th August 2021 and 31st October 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio and orthostatic changes during a 10-minute active standing test as well as Sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the Euroquol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures.

Results: A total of 99 participants (n=33 PASC, n=33 POTS and n=33 healthy controls; median age 32 [18], 85.9% females) were included. Compared to healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (p<0.001), greater heart rate increase during 10-minute active standing test (p<0.001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all p<0.001) and poor HrQoL across all EQ-5D-5L domains (all p<0.001), lower median EQ-VAS (p<0.001) and lower utility scores (p<0.001). The majority (79%) of those with PASC met the internationally established criteria for POTS.

Conclusion: The prevalence of autonomic symptomology or POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.

Trial registration: ANZCTR 12621000476831.

Source: Seeley MC, Gallagher C, Ong E, Langdon A, Chieng J, Bailey D, Page A, Lim HS, Lau DH. High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning. Am J Med. 2023 Jun 28:S0002-9343(23)00402-3. doi: 10.1016/j.amjmed.2023.06.010. Epub ahead of print. PMID: 37391116. https://www.amjmed.com/article/S0002-9343(23)00402-3/fulltext (Full text)

Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies

Abstract:

Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a “probable or confirmed” Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months.

Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid.

Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.

Source: Farigol Hakem Zadeh, Daniel R. Wilson, Devendra K. Agrawal. Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies. Archives of Microbiology and Immunology. 7 (2023): 36-61. http://www.fortunejournals.com/articles/long-covid-complications-underlying-mechanisms-and-treatment-strategies.html (Full text)

Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group

Abstract:

Background: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID.

Methods: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life.

Results: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire.

Conclusions: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.

Source: Cazé AB, Cerqueira-Silva T, Bomfim AP, de Souza GL, Azevedo AC, Brasil MQ, Santos NR, Khouri R, Dan J, Bandeira AC, Cavalcanti LP, Barral-Netto M, Barral A, Barbosa CG, Boaventura VS. Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group. J Glob Health. 2023 May 12;13:06015. doi: 10.7189/jogh.13.06015. PMID: 37166260; PMCID: PMC10173895. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173895/ (Full text)

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19

Abstract:

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL.

In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George’s Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms.

Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic.

Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.

Trial registration: The study is registered on www.ClinicalTrials.gov , NCT04793269.

Source: Malesevic S, Sievi NA, Baumgartner P, Roser K, Sommer G, Schmidt D, Vallelian F, Jelcic I, Clarenbach CF, Kohler M. Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19. Sci Rep. 2023 May 12;13(1):7717. doi: 10.1038/s41598-023-34678-8. PMID: 37173355; PMCID: PMC10175927. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175927/ (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/

How do long COVID patients perceive their current life situation and occupational perspective? Results of a qualitative interview study in Germany

Abstract:

Introduction: Many people experience persistent or new-onset symptoms such as fatigue or cognitive problems after an acute infection with COVID-19. This phenomenon, known as long COVID, impacts physical and mental wellbeing, and may affect perceived quality of life and occupational perspectives likewise. The aim of this study is to gain a deeper understanding of how people with long COVID experience health-related restrictions in their daily life and their occupational situation, and to identify key challenges they face.

Methods: Guided qualitative interviews were conducted with 25 people with long COVID. The interviews were transcribed according to Dresing/Pehl and Kuckartz and analyzed using qualitative content analysis. Afterward, a systematic comparison of the data and a reflection under consideration of lifeworld-theoretical approaches (Berger and Luckmann) were carried out.

Results: The interviews revealed that many participants have severe symptoms which strongly impair them in perform daily and work-related activities, and in their personal interests. Many interviewees already reach their stress limit during routine household activities or childcare. Of the 25 participants, 19 experienced limitations in pursuing leisure activities, and 10 of the 23 interviewees with jobs reported being on sick leave for several months. Several respondents who had vocational reintegration are still affected by ongoing symptoms that affect their work performance considerably. This leads to uncertainty, role conflicts, a decline in social contacts, and decreased incomes, which contribute to an impairment in their quality of life.

Conclusions: This study shows the huge need for specific support for people with long COVID in different areas of life. To prevent people with long COVID from finding themselves in social and economic precarity, decision-makers should develop strategies to systematically support them in their sustainable reintegration into the workforce. The focus should be on creating long COVID-sensitive workplaces, compensating for decreased incomes, and improving access to relief services such as vocational reintegration. We argue, that a shift of perspectives is necessary and that long COVID should be considered rather as a “social disease” with considerably impairments in the social life of those affected.

Trial registration: The study is registered in the German register for clinical trials (DRKS00026007).

Source: Schmachtenberg T, Müller F, Kranz J, Dragaqina A, Wegener G, Königs G, Roder S. How do long COVID patients perceive their current life situation and occupational perspective? Results of a qualitative interview study in Germany. Front Public Health. 2023 Mar 9;11:1155193. doi: 10.3389/fpubh.2023.1155193. PMID: 36969629; PMCID: PMC10034079. https://www.frontiersin.org/articles/10.3389/fpubh.2023.1155193/full (Full text)

The health impact of long COVID: a cross-sectional examination of health-related quality of life, disability, and health status among individuals with self-reported post-acute sequelae of SARS CoV-2 infection at various points of recovery

Abstract:

Objective: The novel Coronavirus (COVID-19) has continued to present a significant burden to global public health efforts. The purpose of this study was to estimate the health-related quality of life, disability, and health status of individuals with self-reported long COVID at various lengths of recovery.

Methods: We conducted a cross-sectional online survey of individuals with self-reported long COVID. Participants were asked to complete the five-item EuroQOL EQ-5D-5L and EQ visual analog scale, the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 and the 10-item Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1.2 short form. Descriptive and inferential statistics were used to characterize the responses and differences across groups.

Results: Eighty-two participants from 13 countries completed the EQ-5D-5L, 73 completed the WHODAS 2.0 and 80 participants completed the PROMIS. The mean EQ-5D-5L utility score was 0.51. The mean WHODAS score was 49.0. In the previous 30 days, participants reported their symptoms affected them for a mean of 24 days, they were totally unable to carry out usual activities for 15 days, and they cut back or reduced activities for 26 days. The mean PROMIS physical health and mental health scores were 10.7 and 8.6, respectively, corresponding to below-average health. No significant differences were detected across time or according to severity of acute infection.

Conclusions: Long COVID presents a significant chronic health burden to adults in the US and abroad. This health burden may persist for many months post-acute infection.

Source: Tak CR. The health impact of long COVID: a cross-sectional examination of health-related quality of life, disability, and health status among individuals with self-reported post-acute sequelae of SARS CoV-2 infection at various points of recovery. J Patient Rep Outcomes. 2023 Mar 21;7(1):31. doi: 10.1186/s41687-023-00572-0. PMID: 36943643; PMCID: PMC10029785. https://jpro.springeropen.com/articles/10.1186/s41687-023-00572-0 (Full text)