Can Early Outpatient Treatment Reduce the Risk of Long COVID?

COVID-19 monoclonal antibodies (mAbs), intravenous remdesivir, and oral antivirals, including Paxlovid (nirmatrelvir/ritonavir) and molnupiravir, have been used for early COVID-19 treatment in individuals at high risk of severe disease progression. However, there is little known about the effect of early therapies on post-COVID-19 conditions, or “long COVID.”

A new study, presented during a poster session at the recent 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023), compared the efficacy of these therapies in reducing COVID-19 hospitalization and death. The investigators also studied whether early outpatient COVID-19 therapy reduced long COVID symptoms after 3 months.

From April 2021-March 2022, the retrospective observational study recruited outpatient adults from a COVID-19 clinic. The patients were stratified into 3 cohorts: mAb recipients, antiviral recipients (oral and short-course remdesivir), and controls (eligible patients who refused treatment).

After 3 months, the investigators evaluated the persistence of long COVID symptoms, including fever, cough, pharyngodynia, dyspnea, chills, nasal congestion, myalgia, headache, dysgeusia/anosmia, and gastrointestinal disease. They also accounted for neuro-behavioral symptoms, such as asthenia, anxiety/mood disorder, and memory or concentration deficit.

The investigators utilized univariate and multivariable logistic models to estimate the associations between each considered outcome and treatment. Models were adjusted by age, sex, vaccination status, early COVID-19 treatment, treatment group, and number of comorbidities (if applicable).

The final study cohort included 649 patients, 51.6% of whom were male, 14% unvaccinated, and with an average age of 67 years. A total of 242 patients were treated with mAbs, 197 with antivirals, and 210 received no treatment. Broken down by comorbidity, 36.7% of all subjects had cerebro-cardiovascular disease, 22% were obese, and 50% had more than 1 comorbidity.

Overall, 29 patients (4.5%) died or were hospitalized. Hospitalization and death were significantly correlated with advanced age.

Data for long COVID at 3 months were only available for 323 patients (49.8% of the original cohort). Females showed a positive association with long COVID, with an Odds Ratio (OR) of 2.14, while men did not. Patients who received antiviral drugs were less likely to develop long COVID, with an OR of 0.43, in comparison to untreated participants. Patients treated with monoclonal antibodies had an OR of 0.48, and a protective benefit against neuro-behavioral symptoms, in comparison to untreated participants.

The investigators concluded that early implementation of COVID-19 therapies can reduce the risk of COVID-19 symptoms after 3 months. Specifically, antivirals were protective against any symptoms of long COVID, while monoclonal antibodies reduced the incidence of neuro-behavioral long COVID symptoms.