COVID-19-related morbidity and mortality in people with multiple long-term conditions: a systematic review and meta-analysis of over 4 million people

Objectives: To describe the direct impact of coronavirus disease 2019 (COVID-19) infection on morbidity and mortality in people with multiple long-term conditions (MLTCs). Design: A systematic review and meta-analysis including observational studies. Setting: Studies conducted between 1 January 2020 and 4 May 2023 across 51 countries were identified from five databases. Participants: A total of 4,084,469 patients with confirmed COVID-19 infection. Main outcome measures: Pooled risk ratios (RRs) for mortality, hospitalisation, severe disease, intensive care unit (ICU) admission and mechanical ventilation were estimated with random effect meta-analysis models. Results: A total of 38,356 studies were identified and 111 included. In most (74%) of the studies, MLTCs referred to having two or more long-term conditions. Others described MLTCs by high weighted indices: the Charlson Comorbidity Index in 11% and the Clinical Frailty Score in 7%. Using the National Institutes of Health quality assessment tool for observational studies, the risk of bias was judged as low and moderate in 86 and 25 studies, respectively. Having MLTCs was associated with increased mortality (RR: 2.61 [95% CI: 2.27 to 3.0]); hospitalisation (2.4 [1.92 to 2.99]); severe disease (2.61 [1.92 to 3.54]); ICU admission (1.22 [1.07 to 1.39]) and mechanical ventilation (1.83 [1.18 to 2.84]) compared with those with no MLTCs. Pooled RRs for adverse outcomes were higher in children and young people compared with all age groups. In meta-regression analyses, men were more likely to need ICU admission (p = 0.013) and mechanical ventilation (p = 0.002). Conclusions: Public health policies, clinical and preventative interventions should prioritise people with MLTCs to minimise direct adverse outcomes from COVID-19 disease.