A Systematic Review of Persistent Symptoms and Residual Abnormal Functioning following Acute COVID-19: Ongoing Symptomatic Phase vs. Post-COVID-19 Syndrome

  1. Glenn Jennings
  2. Ann Monaghan
  3. Feng Xue
  4. David Mockler
  5. Román Romero-Ortuño

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Abstract

Objective: To compare the two phases of long COVID, namely ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life. Design: Systematic review. Data Sources: Electronic search of EMBASE, MEDLINE, ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar between January and April 2021, and manual search for relevant citations from review articles. Eligibility Criteria: Cross-sectional studies, cohort studies, randomised control trials, and case-control studies with participant data concerning long COVID symptomatology or abnormal functioning. Data Extraction: Studies were screened and assessed for risk of bias by two independent reviewers, with conflicts resolved with a third reviewer. The AXIS tool was utilised to appraise the quality of the evidence. Data were extracted and collated using a data extraction tool in Microsoft Excel. Results: Of the 1145 studies screened, 39 were included, all describing adult cohorts with long COVID and sample sizes ranging from 32 to 1733. Studies included data pertaining to symptomatology, pulmonary functioning, chest imaging, cognitive functioning, psychological disorder, and/or quality of life. Fatigue presented as the most prevalent symptom during both OSC and PCS at 43% and 44%, respectively. Sleep disorder (36%; 33%), dyspnoea (31%; 40%), and cough (26%; 22%) followed in prevalence. Abnormal spirometry (FEV1 < 80% predicted) was observed in 15% and 11%, and abnormal chest imaging was observed in 34% and 28%, respectively. Cognitive impairments were also evident (20%; 15%), as well as anxiety (28%; 34%) and depression (25%; 32%). Decreased quality of life was reported by 40% in those with OSC and 57% with PCS. Conclusions: The prevalence of OSC and PCS were highly variable. Reported symptoms covered a wide range of body systems, with a general overlap in frequencies between the two phases. However, abnormalities in lung function and imaging seemed to be more common in OSC, whilst anxiety, depression, and poor quality of life seemed more frequent in PCS. In general, the quality of the evidence was moderate and further research is needed to understand longitudinal symptomatology trajectories in long COVID. Systematic Review Registration: Registered with PROSPERO with ID #CRD42021247846.

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  1. Version published to 10.3390/jcm10245913
  2. ScreenIT

    SciScore for 10.1101/2021.06.25.21259372: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationIn terms of study designs, cross-sectional studies, cohort studies, randomised control trials, and case-control studies were included, while meta-analyses, systematic reviews, narrative reviews, clinical trials, case studies and series, opinion pieces, and non-peer reviewed publications were excluded.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.2 Search strategy: A search strategy was created by a medical librarian that included MeSH terminology related to “post-acute COVID-19”, “long COVID”, “prevalence”, “symptomatology”, “spirometry”, “imaging”, “cognitive”, “psychological burden”, and “quality of life”.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    The full search strategy is shown in Appendix A. EMBASE, MEDLINE
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    , ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar were searched between January and April 2021, with the search was limited to articles published between March 2020 and April 2021.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    2.4 Data extraction: The data from the included studies were extracted by a single reviewer using Microsoft Excel (Appendix B).
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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:
    Therefore, further research is needed to better understand the complex interplay between somatic and psychosocial drivers in long COVID. 4.2 Strengths and weaknesses of the study: A strength of the study is the novel approach to the characterisation of long COVID by considering the OSC and PCS phases, which NICE separated as potentially distinct entities (5) but had not yet been systematically characterised. Another robust aspect of this review is the collation of a total of 39 studies conducted in 17 different countries, which captures the global nature of the COVID-19 pandemic. However, the major limitation of the study resides in the lack of inter-study consistency regarding assessment methods for symptomatology and functional impairments. Many of the studies denoted symptom presence or absence using self-report tools, which are affected by self-report biases (51). Standardised scales were also utilised, however there was no consistency in the selected scales with fatigue alone quantified by 5 distinct objective scales: the Chalder Fatigue Scale (42), the Fatigue Severity Scale (36), the PROMIS (26), and SF-36 (10) scales, and a previously validated unnamed scale (39). This poor inter-study consistency may compromise the validity of the findings, with scales potentially being more or less sensitive or even assessing distinct sub-domains of a symptom. Abnormal patterns in chest imaging were also highly heterogenous through the mixed use of chest x-ray, regular CT, high-reso...

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.06.25.21259372v1 on medRxiv