Authors' objectives: Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority. To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs. Identifying and addressing the long-term health and societal challenges after COVID-19 is a research priority. Capturing the full range of COVID-19 long-term outcomes is essential to support accurate screening and assessment to establish rehabilitation needs of people facing persistent problems in everyday life, measure change over time, and optimise rehabilitation interventions and service provision. To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs.

Authors' results and conclusions: PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants’ median age was 58 years interquartile range (45–68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality. PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities. We collated 116 data sets from 40 countries (IPD = 62,849), comprising 20 RCTs, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Median age of participants was 58 [interquartile range (IQR) (45, 68)], 34,185 (54.4%) were female. We described 158 unique symptoms. Individual studies reported between 1 and 37 symptoms. We categorised 137 unique assessment instruments, predominantly describing ICF-body functions. After COVID-19 infection: Lower overall perception of health by EuroQoL visual analogue scale (EuroQoL VAS) was associated with increasing age [RoD = 1.006, 95% CI (1.004 to 1.009)], increasing body mass index [BMI, RoD = 0.983, 95% CI (0.978 to 0.988)], female sex [RoD = 1.15, 95% CI (1.07 to 1.24)], initial hospitalisation for COVID-19 [RoD = 0.70, 95% CI (0.60 to 0.82)], presence of existing immunosuppression [RoD = 0.75, 95% CI (0.67, 0.83)], cardiac conditions [RoD = 0.73, 95% CI (0.63 to 0.86)] and lung disease [RoD = 0.89, 95% CI (0.83 to 0.97)] at 3–6 months (D = 3, IPD = 1766); initial hospitalisation for COVID-19 [RoD = 0.66, 95% CI (0.58 to 0.75)], female sex [RoD = 1.17, 95% CI (1.10 to 1.25)], unemployment [RoD = 0.78, 95% (0.70 to 0.87)], presence of existing obesity [RoD = 0.79, 95% CI (0.73 to 0.85)], immunosuppression [RoD = 0.74, 95 CI (0.67, 0.83)], diabetes [RoD = 0.79, 95% CI (0.70 to 0.90)], lung disease [RoD = 0.89, 95% CI (0.82 to 0.96)] and chronic kidney disease [RoD = 0.72 (0.57 to 0.90) at 9–12 months (D = 4, IPD = 2818); initial hospitalisation for COVID-19 [RoD = 0.61, 95% CI (0.51 to 0.73)], lower education level [RoD = 0.89, 95% CI (0.82 to 0.97)], presence of existing mental/behavioural disorders [RoD = 0.66, 95% CI (0.60 to 0.72)], immunosuppression [RoD = 0.72, 95% CI (0.64 to 0.82)], diabetes [RoD = 0.76, 95% CI (0.68 to 0.86)], lung disease [RoD = 0.88, 95% CI (0.81 to 0.95)] and chronic kidney disease [RoD = 0.75, 95% CI (0.61 to 0.93)], beyond 12 months (D = 3, IPD = 1932). Poorer cognitive function by Montreal Cognitive Assessment was associated with increasing age [RoD = 0.992, 95% CI (0.989 to 0.995)], other ethnicity [RoD = 0.76, 95% CI (0.67 to 0.85)], lower education level (did not complete primary education RoD = 0.54, 95% CI (0.41 to 0.71)] and presence of existing mental/behavioural disorders [RoD = 0.87, 95% CI (0.78 to 0.96)] at 3–6 months (D = 2, IPD = 839); and increasing age [RoD = 0.989, 95% CI (0.984 to 0.994)], Black [RoD = 0.53, 95% CI (0.40 to 0.72)], Asian [RoD = 0.80, 95% CI (0.68 to 0.95)] and other ethnicities [RoD = 0.63, 95% CI (0.45 to 0.90)] and lower education level (did not complete primary education RoD = 0.67, 95% CI (0.47 to 0.94)] beyond 12 months (D = 2, IPD = 566). Higher anxiety by Hospital Anxiety and Depression-A scale was associated with female sex [RoD = 0.80, 95% CI (0.74 to 0.87)], younger age [RoD = 0.988, 95% CI (0.985 to 0.991)], presence of existing lung disease [RoD = 1.28, 95% CI (1.17 to 1.40)] and neurological conditions [RoD = 1.32, 95% CI (1.10 to 1.58)] in initially hospitalised populations at 3–6 months (D = 5, N = 1394); female sex [RoD = 0.78, 95% CI (0.70 to 0.87)] and presence of existing circulatory disorders [RoD = 1.24, 95% CI (1.06 to 1.45)] in initially non-hospitalised populations at 3–6 months (D = 2, N = 569); initial hospitalisation for COVID-19 [RoD = 1.20, 95% CI (1.08 to 1.33)], female sex [RoD = 0.82, 95% CI (0.78 to 0.87)], presence of existing lung disease [RoD = 1.19, 95% CI (1.07 to 1.33)] and in unemployed smokers [RoD = 1.19, 95% CI (1.04 to 1.36)] at 9–12 months (D = 3, IPD = 1679); initial hospitalisation for COVID-19 [RoD = 1.30, 95% CI (1.17 to 1.45)], female sex [RoD = 0.84, 95% CI (0.79 to 0.88)], younger age [RoD = 0.988, 95% CI (0.985 to 0.991)] and those not in employment [RoD = 1.18, 95% CI (1.10 to 1.26)] beyond 12 months (D = 4, IPD = 1340). Higher depression by Hospital Anxiety and Depression-D scale was associated with younger age [RoD = 0.990, 95% CI (0.987 to 0.994)], female sex [RoD = 0.78, 95% CI (0.71 to 0.86)], presence of existing lung disease [RoD = 1.24, 95% CI (1.12 to 1.37)] and mental/behavioural disorders [RoD = 1.61, 95% CI (1.44 to 1.81)] at 3–6 months (D = 3, IPD = 1001); younger age [RoD = 0.998, 95% CI (0.996 to 0.999)], female sex [RoD = 0.89, 95% CI (0.86 to 0.93)], people not in employment [RoD = 1.30, 95% CI (1.20 to 1.42)], presence of existing diabetes [RoD = 1.33, 95% CI (1.17 to 1.51)], cancer [RoD = 1.19 [1.07, 1.32)] or smoking [RoD = 1.11, 95% CI (1.06 to 1.18)] at 9–12 months (IPD = 1722, D = 4); and initial hospitalisation for COVID-19 [RoD = 1.15, 95% CI (1.06 to 1.24)], female sex [RoD = 0.91, 95% CI (0.88 to 0.95)], obesity [RoD = 1.08, 95% CI (1.02 to 1.13)], smoking [RoD = 1.09, 95% CI (1.02 to 1.17)] and for people not in employment [RoD = 1.07, 95% CI (1.02 to 1.13)], beyond 12 months (D = 4, IPD = 1286). Higher stress by Depression, Anxiety and Stress Scale-21 was associated with smoking [RoD = 1.26, 95% CI (1.12 to 1.42)], presence of diabetes [RoD = 1.42, 95% CI (1.02 to 1.97)], immunosuppression [RoD = 1.55, 95% CI (1.12 to 2.15)] and female sex [RoD = 0.64, 95% CI (0.57 to 0.72)] at 9–12 months (D = 2, IPD = 1344); female sex [RoD = 0.66, 95% CI (0.56 to 0.78)], smoking [RoD = 1.34, 95% CI (1.13 to 1.59)] and not being in employment [RoD = 1.50, 95% CI [1.15 to 1.97)] beyond 12 months (D = 2, IPD = 698). Worse PTSD by revised Impact of Event Scale was associated with younger age [RoD = 0.991, 95% CI (0.985 to 0.996)], female sex [RoD = 0.72, 95% CI (0.62 to 0.83)] and presence of existing lung disease [RoD = 1.30, 95% CI (1.10 to 1.53)] at 3–6 months (D = 5, IPD = 1036). Greater fatigue by Fatigue Assessment Scale was associated with younger age [RoD = 0.997, 95% CI (0.995 to 0.998)], female sex [RoD = 0.87, 95% CI (0.83 to 0.90)], presence of existing lung disease [RoD = 1.12, 95% CI (1.08 to 1.17)], neurological conditions [RoD = 1.21, 95% CI (1.10 to 1.33)] and musculoskeletal conditions [RoD = 1.10, 95% CI (1.04 to 1.16)] at 3–6 months (D= 3, IPD= 1030); younger age [RoD = 0.998, 95% CI (0.997 to 0.999)], female sex [RoD = 0.90, 95% CI (0.88 to 0.93)], presence of existing immunosuppression [RoD = 1.15, 95% CI (1.06 to 1.24)] and lung disease [RoD = 1.08, 95% CI (1.03 to 1.13)] at 9–12 months (D = 5, IPD = 1594); and female sex [RoD = 0.90, 95% CI (0.85 to 0.94)] and presence of existing mental/behavioural disorders [RoD = 1.26, 95% CI (1.18 to 1.34)] beyond 12 months (D = 2, IPD = 722). Poorer ability to cope with daily life by Nottingham Extended Activities of Daily Living Scale was associated with female sex [RoD = 1.30, 95% CI (1.18 to 1.43)], presence of existing lung disease [RoD = 0.72, 95% CI (0.65 to 0.80)], chronic kidney disease [RoD = 0.82, 95% CI (0.67 to 0.995)], increasing age [RoD = 0.995, 95% CI (0.992 to 0.999)] and certain lower education strata (completed high school RoD = 0.82, 95% CI (0.74 to 0.89)] at 3–6 months (D = 2, IPD = 1086); and increasing age [RoD = 0.990, 95% CI (0.984 to 0.996)], female sex [RoD = 1.24, 95% CI (1.07 to 1.45)] and certain lower education strata (did not complete primary education RoD = 0.53, 95% CI (0.33 to 0.84)] beyond 12 months (D = 2, IPD = 574). Poorer walking ability by 6-minute walk test was associated with increasing age [estimate of difference = −1.54, 95% CI (−2.18 to −0.91)], female sex [estimate of difference = 46.25, 95% CI (27.80 to 64.71)], increasing BMI [estimate of difference = −4.22, 95% CI (−5.81 to −2.62)], presence of existing cardiac conditions [estimate of difference = −77.46, 95% CI (−113.39 to −41.53)], lung disease [estimate of difference = −31.71, 95% CI (−53.73 to −9.70)] and female sex without cardiac conditions [estimate of difference = 56.73, 95% CI (14.05 to 99.42)] at 3–6 months (D = 6, IPD = 567). Poorer mobility by Short Physical Performance Battery was associated with increasing age [RoD = 0.989, 95% CI (0.986 to 0.992)], female sex [RoD = 1.35, 95% CI (1.25 to 1.47)], presence of existing lung disease [RoD = 0.78, 95% CI (0.72 to 0.85)], chronic kidney disease [RoD = 0.72, 95% CI (0.59 to 0.88)], neurological conditions [RoD = 0.67, 95% CI (0.54 to 0.83)], musculoskeletal conditions [RoD = 0.79, 95% CI (0.71 to 0.89)] and diabetes at 3–6 months (D = 2, IPD = 1080). Worse breathlessness was associated with increasing COVID-19 severity (ventilated population RoD = 1.29, 95% CI (1.08 to 1.54)], presence of existing lung disease [RoD = 1.11, 95% CI (1.02 to 1.20)], immunosuppression [RoD = 1.33, 95% CI (1.15 to 1.54)], obesity [RoD = 1.19, 95% CI (1.10 to 1.29)] and female sex [RoD = 0.91 [0.87, 0.96)] at 3–6 months (D = 3, IPD = 744); increasing age [RoD = 1.002, 95% CI (1.001 to 1.003)], increasing age in the presence of existing lung disease [RoD = 1.005, 95% CI (1.002 to 1.008)], presence of obesity [RoD = 1.18, 95% CI (1.12 to 1.25)], existing circulatory disorders [RoD = 1.11, 95% CI (1.06 to 1.16)], immunosuppression [RoD = 1.21, 95% CI (1.11 to 1.32)], female sex [RoD = 0.91, 95% CI (0.88 to 0.94)] and initial hospitalisation for COVID-19 [RoD = 1.18, 95% CI (1.11 to 1.25)] at 9–12 months (D = 3, IPD = 1277); increasing age [RoD = 1.003, 95% CI (1.002 to 1.005)], initial hospitalisation for COVID-19 [RoD = 1.24, 95% CI (1.14 to 1.36)], presence of obesity [RoD = 1.21, 95% CI (1.11 to 1.31)] circulatory disorders [RoD = 1.10, 95% CI (1.03 to 1.18)] and female sex [RoD = 0.88, 95% CI (0.84 to 0.92)], beyond 12 months (D = 3, IPD = 655). Mortality was associated with increasing age [RoD = 1.068, 95% CI (1.052 to 1.074)], male sex [RoD = 1.31, 95% CI (1.15 to 1.50)], existing cancer [RoD = 1.23, 95% CI (1.04 to 1.46)], chronic kidney disease [RoD = 1.49, 95% CI (1.19 to 1.72)], dementia/Alzheimer’s [RoD = 1.56, 95% CI (1.31 to 1.86)] and lung disease [RoD = 1.25, 95% CI (1.07 to 1.46)] in hospitalised non-ventilated populations (D = 5, IPD = 5027); and increasing age [RoD = 1.036, 95% CI (1.028 to 1.044)], male sex [RoD = 1.27, 95% CI (1.05 to 1.54)], existing diabetes [RoD = 1.56, 95% CI (1.30 to 1.87)], chronic kidney disease [RoD = 1.47, 95% CI (1.08 to 2.00)] and liver disease [RoD = 2.10, 95% CI (1.37 to 3.22)] in hospitalised and ventilated populations (D = 9, IPD = 969). Later hospitalisation after infection was associated with increasing age [OR = 1.02, 95% CI (1.01 to 1.02)], existing cerebrovascular disease [OR = 1.68, 95% CI (1.12 to 2.53)], diabetes [OR = 1.56, 95% CI (1.23 to 1.98)], chronic kidney disease [OR = 1.67, 95% CI (1.23 to 2.26)], cancer [OR = 2.64, 95% CI (2.02 to 3.44)] and current smoking status [OR = 0.76, 95% CI (0.61 to 0.94)] (D = 2, IPD = 1336). We observed no significant impact of COVID-positivity on later hospitalisation, compared with COVID-negative participants. We were therefore unable to calculate the additional costs of COVID-19 rehospitalisation. Worse HRQoL by EuroQoL-derived health utilities was associated with exposure to COVID-19 [estimate = −0.03, 95% CI (−0.06 to −0.01)] female sex [estimate = −0.054, 95% CI (−0.07 to −0.04)] initial hospitalisation for COVID-19 [estimate = −0.07, 95%CI [−0.1 to −0.04)], presence of diabetes [estimate = −0.06, 95% CI (−0.09 to −0.04)], obesity [estimate = −0.05, 95% CI (−0.06 to −0.04)], existing lung disease [estimate = −0.05, 95% CI (−0.07 to −0.04)], chronic kidney disease [estimate = −0.05, 95% CI (−0.09 to −0.01)]; better HRQoL was seen in non-smokers [estimate = 0.02, 95% CI (0.01 to 0.04)], people with a higher education status [0.02, 95% CI (0.01 to 0.04)] and those in employment [estimate = 0.04, 95% CI (0.03 to 0.05)]. Initial hospitalisation with COVID-19 consistently resulted in lower HRQoL that did not appear to recover for up to 2 years after the initial COVID-19 infection. Heterogeneity was low for 34/37 models; using a GRADE-informed assessment of models, 22/37 were of moderate and 11/37 were of low quality. PRECIOUS contribute to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights the disproportionate impact of poorer long-term outcomes in female sex, and those with pre-existing comorbidities.

Authors' methods: Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19. Contributed data were collected in clinical, community and research settings. Interventions from original studies were included as covariates in models. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019–November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers. Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3–6 months, 9–12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I2. Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system. We conducted systematic identification of COVID-19 data sets and meta-analysis of individual participant data (IPD) on long-term outcomes after COVID-19. We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), World Health Organization (WHO) Global Index Medicus, Epistemonikos, LitCOVID; from November 2019 to November 2021; CENTRAL, MEDLINE, EMBASE, CINAHL, WHO International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for relevant studies reporting on > 10 people from cohort, case-control, survey or randomised controlled trial (RCT) studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28 days after COVID-19 onset. Principal investigators were invited to contribute data. Data were originally collected in clinical, community and research settings in the primary studies. Study descriptors, demography, equity, symptoms and outcomes of interest were extracted by two independent reviewers and cross-checked by data contributors. We described demography, equity, mapped outcome assessment tools to the International Classification of Functioning, Disability and Health (ICF), and described symptom prevalence over time. A one-stage meta-analysis approach described factors associated with available outcomes at 3–6 months, 9–12 months and beyond 12 months, for n > 500 IPD and > 1 data set. Interventions in original studies were included as covariates in long-term outcome models where appropriate. Findings were presented as ratio of difference (RoD), point estimates or odds ratio (OR) and 95% confidence interval (95% CI). Study quality was described using the Mixed Methods Appraisal Tool; individual models were appraised using a Grading of Recommendations Assessment, Development and Evaluation (GRADE)-informed approach and heterogeneity was described using the I2 statistic. Outcomes examined included physical functioning and mental health in the context of quality-of-life instruments, overall perception of health, sleep, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder (PTSD), fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life (HRQoL). Data were primarily collated from high-income countries; we lacked adequate data on ethnicity and measures of health inequity, which would have enhanced our analyses. No data on healthcare resource use, apart from later hospitalisation, were available; therefore, we were unable to calculate additional costs to the healthcare system for those with COVID-positivity. Use of secondary data for IPD meta-analyses limited available covariates for adjusted analyses to those included in primary data sets. The final models reflected variable significance within the context of data availability and were limited to long-term outcomes of interest to the primary research.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hsdr/NIHR132895

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hsdr/GJMA0602

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GJMA0602

Organisation Name: NIHR Health Services and Delivery Research programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk