Long COVID after mild infection may persist for months, resolve within a year

Patients with mild COVID-19 may encounter a few health concerns for several months following SARS-CoV-2 infection, but these outcomes tend to resolve within a year from diagnosis, reveals a study.

“This nationwide dataset of patients with mild COVID-19 suggests that mild disease does not lead to serious or chronic long-term morbidity in the vast majority of patients and adds a small continuous burden on healthcare providers,” the researchers said.

“Importantly, the risk for lingering dyspnoea was reduced in vaccinated patients with breakthrough infection compared with unvaccinated people, while risks of all other outcomes were comparable,” they added.

A retrospective nationwide cohort study was conducted to determine the clinical sequelae of long COVID for a year after infection in patients with mild disease and to explore its relationship with age, sex, SARS-CoV-2 variants, and vaccination status.

The researchers used electronic medical records from an Israeli nationwide healthcare organization to identify 1,913,234 Maccabi Healthcare Services members who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. The team assessed the risk of an evidence-based list of 70 long COVID outcomes in unvaccinated patients with SARS-CoV-2 matched to uninfected individuals, adjusted for age and sex and stratified by SARS-CoV-2 variants. They also assessed the risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls.

Hazard ratios (HRs) and risk differences (RDs) per 10,000 patients, measured during the early (30‒180 days) and late (180‒360 days) time periods after infection, were used to compare the risks.

Long COVID outcomes

COVID-19 infection contributed to higher risks in early and late periods for anosmia and dysgeusia (early period: HR, 4.59, 95 percent confidence interval [CI], 3.63‒5.80; RD, 19.6, 95 percent CI, 16.9‒22.4; late period: HR, 2.96, 95 percent CI, 2.29‒3.82; RD, 11.0, 95 percent CI, 8.5‒13.6), cognitive impairment (early period: HR, 1.85, 95 percent CI, 1.58‒2.17; RD, 12.8, 95 percent CI, 9.6‒16.1; late period: HR, 1.69, 95 percent CI, 1.45‒1.96; RD, 13.3, 95 percent CI, 9.4‒17.3), and dyspnoea (early period: HR, 1.79, 95 percent CI, 1.68‒1.90; RD, 85.7, 95 percent CI, 76.9‒94.5; late period: HR, 1.30, 95 percent CI, 1.22‒1.38; RD, 35.4, 95 percent CI, 26.3‒44.6). [BMJ 2023;380:e072529]

Likewise, COVID-19 correlated with increased risks for weakness (early period: HR, 1.78, 95 percent CI, 1.69‒1.88; RD, 108.5, 95 percent CI, 98.4‒118.6; late period: HR, 1.30, 95 percent CI, 1.22‒1.37; RD, 50.2, 95 percent CI, 39.4‒61.1) and palpitations (early period: HR, 1.49, 95 percent CI, 1.35‒1.64; RD, 22.1, 95 percent CI, 16.8‒27.4; late period: HR, 1.16, 95 percent CI, 1.05‒1.27; RD, 8.3, 95 percent CI, 2.4‒14.1), and with significant but reduced excess risk for streptococcal tonsillitis and dizziness.

Hair loss, chest pain, cough, myalgia, and respiratory disorders also significantly increased but only during the early period.

Notably, minor differences existed between male and female patients, and children presented with fewer outcomes than adults during the early phase of COVID-19, most of which resolved in the late period. These findings remained consistent across variants of SARS-CoV-2.

Vaccination

Interestingly, vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea but similar risk for other outcomes relative to their unvaccinated counterparts.

“In Israel, the BNT162b2 SARS-CoV-2 mRNA vaccine was evaluated in a nationwide vaccination campaign and effectively reduced symptomatic COVID-19, hospital admissions, severe disease, and death,” the researchers said. [N Engl J Med 2021;384:1412-1423; N Engl J Med 2021;385:1393-1400]

“Recent studies have also shown that vaccination results in reduction in the risk of the postacute sequelae of COVID-19,” they added. [Brain Behav Immun 2022;103:154-162; Nat Med 2022;28:1461-1467; Vaccines (Basel) 2022;10:652]

In the current study, the association between vaccination status and long-term health outcomes was examined in patients with breakthrough infections and mild disease course. However, protection from acquisition of infection or from severe illness, hospital admission, and death was not measured; thus, it did not contradict any of these proven benefits.

“Our findings suggest that mild COVID-19 in vaccinated people was significantly associated with reduced risk for dyspnoea compared with unvaccinated patients up to 3 months after infection,” the researchers said. “This is in accordance with reports showing that vaccination before SARS-CoV-2 breakthrough infection partially reduced the risk of postacute sequalae.” [Nat Med 2022;28:1461-1467]