Gaps in Long COVID treatments research: A scoping review

Background Long COVID affects 6 to 10% of people following SARS-CoV-2 infection. It has been documented worldwide, with over 200 symptoms reported. This scoping review assesses the evidence on Long COVID treatments to identify gaps in the evidence-base to inform research prioritisation. Methods We searched four databases (MEDLINE, Embase, Cochrane’s Trial register, Epistemonikos) supplemented by a grey literature search up to April 2023. Two reviewers screened articles and extracted data. Data were analysed using a thematic approach. Results Of 3675 records identified, 26 studies were included. Most were in high-income countries (92%), with two in upper-middle-income countries (8%). None reported inclusion of children, nor pregnant women and only 37.5% included adults over 64 years. Five (20.8%) presented ethnicity data, of these 92.9% of participants were of white ethnicity. Treatments included nutritional supplements (46%), conventional medicines (38%), hyperbaric medicine (8%), COVID-19 vaccination (4%) and complementary, alternative medicine (4%). Conclusion This scoping review highlights that more than four years after the start of the pandemic, research gaps remain for Long COVID treatments. There is a lack of research in low-income countries, despite trials being best placed locally to reflect different population demographics. There is a lack of inclusion of population sub-groups, particularly children, pregnant women and ethnic minority groups. Inclusion of these groups in future research is important given they may be at a higher risk of adverse outcomes of COVID-19, and a lack of appropriate treatments for Long COVID may contribute to the widening of health inequalities.</p

Types of outcomes reported.

<p>Types of outcomes reported.</p

Facilitators and barriers to integrated cervical cancer and HIV care.

<p>The tables shows barriers and facilitators mentioned in the results or discussion.</p

Results of the studies evaluating integration.

<p>Results of the studies evaluating integration.</p

Type of integration and cervical cancer services provided.

<p>The table shows the integration models described in the included studies.</p

Model 3—Complex program of integration and coordination described.

<p>Model 3—Complex program of integration and coordination described.</p

Model 1—Within clinic integration using internal staff.

<p>Model 1—Within clinic integration using internal staff.</p

Model 2—Coordination between co-located clinics/specialists.

<p>Model 2—Coordination between co-located clinics/specialists.</p

Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.</p