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Meta-Analysis
. 2023 Jul 12;32(169):220254.
doi: 10.1183/16000617.0254-2022. Print 2023 Sep 30.

SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis

J Daniel Kelly  1 , Tristan Curteis  2 , Aaditya Rawal  3 , Molly Murton  4 , Laura J Clark  2 , Zarena Jafry  3 , Rikisha Shah-Gupta  5 , Mark Berry  5 , Aprille Espinueva  6 , Linda Chen  6 , Mazin Abdelghany  6 , Daniel A Sweeney  7 , Jennifer K Quint  8
Affiliations
Meta-Analysis

SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis

J Daniel Kelly et al. Eur Respir Rev. .

Abstract

Background: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC.

Methods: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses.

Results: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)).

Conclusions: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.

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Conflict of interest statement

Conflict of interest: J.D. Kelly received consulting fees from Gilead. T. Curteis, A. Rawal, M. Murton, L.J. Clark and Z. Jafry are employees of Costello Medical, which received payment from Gilead Sciences for analytical services for this study. R. Shah-Gupta is an employee of Gilead Sciences. M. Berry is an employee of, and owns stock in, Gilead Sciences. A. Espinueva was an employee of, and owned stock in, Gilead Sciences at the time of the study. L. Chen is an employee of, and owns stock in, Gilead Sciences and owns stocks in Pfizer. M. Abdelghany is an employee of, and owns stock in, Gilead Sciences. D.A. Sweeney has no conflicts of interest to report. J.K. Quint received consulting fees from Gilead, AstraZeneca and Evidera, and received research grants from HDR UK.

Figures

FIGURE 1
FIGURE 1
a) Histogram summarising frequency of reporting of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) outcomes in extracted studies. Studies that reported on more than one follow-up time-point are included in the plot at each time-point they reported on. b) Sunburst plot summarising frequency of reporting of PASC outcomes in extracted studies. The sunburst plot summarises the frequency of reporting of PASC symptoms across the extracted studies, with the inner ring divided by symptom category and the outer ring reporting all symptoms within each category. The size of each section in both the inner and the outer ring reflects the number of primary publications that reported each symptom. The starburst plot does not contain any information on combined symptoms or the percentage of patients experiencing at least one symptom. COVID-19: coronavirus disease 2019; ENT: ear–nose–throat.
FIGURE 2
FIGURE 2
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. #: studies were required to have the aim of characterising “long COVID”. CDSR: Cochrane Database of Systematic Reviews; CENTRAL: Cochrane Central Register of Controlled Trials; WHO ICTRP: World Health Organization International Clinical Trials Registry Platform; QoL: quality of life; COVID-19: coronavirus disease 2019.
FIGURE 3
FIGURE 3
Key study characteristics assessed in feasibility assessment: a) coronavirus disease 2019 (COVID-19) disease severity (reported by 13 out of 52 studies), b) oxygen status (reported by 29 out of 52 studies), c) duration of hospitalisation (reported by 30 out of 52 studies) and d) intensive care unit (ICU) admission (reported by 34 out of 52 studies). Disease severity was recorded either at admission or during the period of hospitalisation; oxygen status was recorded over the period of hospitalisation. Duration of hospitalisation was reported by studies as either mean or median; in the heterogeneity assessment these values were assumed to be equivalent as per standard practice and the standard deviation was calculated from the interquartile range for studies reporting the median. IMV: invasive mechanical ventilation.
FIGURE 4
FIGURE 4
Meta-analysis summary estimates for each of the 13 symptoms of interest at each of the three time periods of interest. Combined anosmia and ageusia and combined arthralgia and myalgia were both extracted as a single outcome for when studies reported both anosmia and ageusia or arthralgia and myalgia as a single outcome. NR: not reported.
FIGURE 5
FIGURE 5
Meta-analysis summary estimates for fatigue at each of the three time periods of interest. #: the Fernández-de-las-Peñas et al. [28, 47, 48, 50] studies were conducted by the same group of authors but included distinct patient groups. I2>50% and p<0.05 indicates substantial heterogeneity.
FIGURE 6
FIGURE 6
Meta-analysis summary estimates for dyspnoea/breathlessness at each of the three time periods of interest. #: the Fernández-de-las-Peñas et al. [28, 47, 48, 50] studies were conducted by the same group of authors but included distinct patient groups. I2>50% and p<0.05 indicates substantial heterogeneity.
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