Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study

Abstract

Objectives: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status.

Design: Retrospective nationwide cohort study.

Setting: Electronic medical records from an Israeli nationwide healthcare organisation.

Population: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.

Main outcome measures: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.

Results: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.

Conclusions: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Fig 1

Study population and cohort selection. Schematic representation of cohort and sub-cohorts selection. People who were included in matched negative SARS-CoV-2 cohort and tested positive during study were added to positive cohort and re-matched. SARS-CoV-2 variants were determined according to variant dominance at time of polymerase chain reaction (PCR) testing

Fig 2

Risk for long term health outcomes after SARS-CoV-2 infection in patients with mild disease. Hazard ratios and risk differences per 10 000 patients of reported health outcomes (persistent symptoms) in unvaccinated SARS-CoV-2 infected patients with mild covid-19 during early and late periods

Fig 3

Risk for long term health outcomes after SARS-CoV-2 infection in patients with mild disease. Hazard ratios and risk differences per 10 000 patients of reported health outcomes (acute diagnoses, infectious diseases, chronic conditions) in unvaccinated SARS-CoV-2 infected patients with mild covid-19 during early and late periods. TIA=transient ischaemic attack

Fig 4

Monthly risk of significant reported outcomes in unvaccinated infected patients. Hazard ratios (with 95% confidence intervals) for reported health outcomes that were significantly different for unvaccinated people infected with SARS-CoV-2 compared with matched uninfected people. Monthly risk of reported outcomes was evaluated longitudinally during early and late periods

Fig 5

Risk of significant reported outcomes in different age subgroups. Hazard ratios and risk differences (with 95% confidence intervals) for all reported health conditions (supplementary tables S4a-l) were evaluated during early and late (orange) periods

Fig 6

Risk of significant reported outcomes in male and female patients. Hazard ratios and risk differences (with 95% confidence intervals) for all reported health conditions (supplementary tables 5b and5c) were evaluated during early and late periods

Fig 7

Hazard ratios (with 95% confidence intervals) for long covid health outcomes 30-90 days after infection for unvaccinated versus vaccinated patients. Health outcomes that were significantly related to SARS-CoV-2 infection were assessed in vaccinated and unvaccinated patients (supplementary tables 8a-b)