LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES

  1. Hassaan Ahmed
  2. Kajal Patel
  3. Darren Greenwood
  4. Stephen Halpin
  5. Penny Lewthwaite
  6. Abayomi Salawu
  7. Lorna Eyre
  8. Andrew Breen
  9. Rory O’Connor
  10. Anthony Jones
  11. Manoj Sivan

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Abstract

Objective

To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission.

Design

Systematic review and meta-analysis of the literature.

Data sources

Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up.

Results

The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term.

Conclusions

The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.16.20067975: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThere were too few studies to formally explore the sources of heterogeneity through meta-regression (e.g. by mean age, disease, % male, or level of evidence) or examine potential small-study effects such as publication bias through funnel plots.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    , EMBASE (1974 to March 31st, 2020)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    CINAHL Plus (1937 to March Week 3 2020) and PsycINFO (1806 to Match Week 3 2020).
    PsycINFO
    suggested: (PsycINFO, RRID:SCR_014799)
    Terms were entered as MeSH terms where available for each database, otherwise these were searched as keywords in the title, abstract and subject headings.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This could be due to circulatory limitation, muscle weakness, critical illness neuropathy and myopathy (CINM) and deconditioning30. The 6MWD is also reduced at 3 months and slowly improves by 12 months44,45. We know from other literature that such chronic weakness may be present in patients even 5 years after ICU admission, therefore, rehabilitation needs of these patients can be prolonged46. Early rehabilitation combining mobilisation with strengthening exercises may improve exercise tolerance in these patient groups as it has substantial evidence for improving weakness and functional independence in CINM47. Our meta-analysis showed that around a third of CoV survivors may have psychological conditions such as PTSD, depression and anxiety beyond 6 months. These estimates are much higher than the prevalence of these conditions reported as part of post-ICU syndrome in medical and surgical patients48. This indicates that the long-lasting mental health impact is not from serious illness alone, but also from factors such as fear49, stigma37 and quarantine50, all of which also apply to COVID-1951. The neuropsychiatric aspects of CoV infections are not very well known yet and priorities and strategies for mental health science research have already been set out52. SF-36 scores for role limitations in CoV survivors were particularly low compared to healthy individuals. Tansey et al. (2007)14 reported that 17% CoV survivors had not returned to their previous level of working even at ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.04.16.20067975 on medRxiv
  3. Version published to 10.2340/16501977-2694