According to the World Health Organization, as of the end of 2023, COVID-19 has resulted in over 770 million infections and over 7 million deaths worldwide [1]. While the introduction of comprehensive vaccine programs has reduced the number of deaths due to COVID-19 [2], the virus that causes COVID-19, SARS-CoV-2, continues to evolve and the number of new infections continues to rise [1]. The global impact of COVID-19 has been substantial, and the repercussions of the disease continue to impact healthcare resources, economies, and individuals. In-depth interviews with patients indicate that the impact of living with COVID-19 is significant, and a substantial part of this is due to symptoms, which are frequently persistent [3, 4].

The symptoms experienced by patients with COVID-19 are heterogeneous and vary in duration from days to months and even years [4,5,6,7]. For example, patients with COVID-19 report systemic symptoms, such as fatigue, weakness, and joint pain, along with symptoms of the upper and lower respiratory tract (e.g., dyspnea), the gastrointestinal system, depression/anxiety, and cognitive functioning [3, 5, 8, 9]. While some symptoms like headache, fever, and chills are associated with early stages of the infection and resolve within days, other symptoms such as cough, dyspnea, and loss of taste/smell tend to occur later in the disease trajectory and can become persistent [10]. Studies have estimated that nearly three-quarters of patients have persistent COVID-19-related symptoms, i.e., symptoms lasting at least 60 days after diagnosis [9, 11]. Symptom manifestation is not only burdensome but negatively impacts patients’ daily lives [3, 12, 13]. Specifically, patients with COVID-19 report difficulties with self-care, activities of daily living, and emotional/psychological well-being [3], which can persist months after the initial infection [4]. The impact of COVID-19 on patients has been so profound that there is a call to action for the mental well-being of patients, including increased attention to mental health [14]. Furthermore, research has found that patients with certain risk factors (e.g., higher age, obesity, and comorbidities such as diabetes mellitus) are more likely to experience severe symptoms, even after the introduction of vaccine programs [10, 15].

At the start of the pandemic, clinical trials investigating therapeutics for COVID-19 typically focused on reducing mortality and hospitalizations. However, as the introduction of vaccine programs has reduced the number of severe COVID-19 cases, the focus of outcomes has shifted, and reliable data on the long-term impact of symptoms on patients’ daily lives has become increasingly important for individual patient care, healthcare resource planning, and development of public health policy. Patient-reported outcomes (PROs) are now central to the management of patients with COVID-19, as they reveal the effect of COVID-19 on patients’ health-related quality of life (HRQoL) and inform physicians of possibly more serious complications [16]. PROs directly measure the experience from the patient perspective, without third-party judgment or interpretation from others such as clinicians or researchers [17], and therefore assist regulators with the evaluation of treatment benefit and risk [18]. Their importance in clinical trials and drug approvals was further affirmed when the US Food and Drug Administration (FDA) issued guidance for approaches that measure and analyze common COVID-19-related symptoms in outpatient clinical trials [18]. Furthermore, the benefits of PROs extend beyond clinicians and regulators to inform treatment decisions with patients [19].

Monoclonal antibodies (mAbs) have been used therapeutically since 1985, including in the management of cancers, autoimmune diseases, and infections. They are widely regarded as being highly specific for their target antigen, are generally well tolerated, and can be rapidly developed. In the race to decrease the healthcare, patient, and economic burden of COVID-19, anti-SARS-CoV-2 mAbs were investigated across different settings and patient groups, and found to effectively prevent hospitalizations and other complications associated with COVID-19 [20,21,22,23]. Consequently, four mAbs received Emergency Use Authorizations from the FDA for the treatment of COVID-19; however, none are currently approved in the USA as the currently dominant variants (Omicron lineage) are not thought to be susceptible to the currently available anti-SARS-CoV-2 mAbs [24]. Given the efficacy seen with earlier mAbs in the management of COVID-19 and the continual increase in infection rates, a number of new mAbs are currently under investigation, and clinicians, patients, and policy decision makers are keen to see if this next generation of anti-SARS-CoV-2 mAbs can positively impact clinical endpoints, such as deaths and hospitalizations, but also, and maybe more importantly, PROs, such as symptom relief, activities of daily living, and emotional/psychological well-being.

To date, there is limited evidence from controlled studies regarding patients’ experiences with COVID-19 and the impact of mAbs on their symptoms, functioning, and overall HRQoL. An adaptive, randomized phase 1/2/3 trial conducted before the emergence of Omicron-lineage variants found that a mAb combination (casirivimab plus imdevimab [CAS + IMD]) in patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 decreased time to symptom resolution by 4 days compared to placebo [23]. The difference was evident from day 3 and consistent across patient subgroups [23]. Here, we further assessed the effects of a mAb combination on symptoms, daily function, and overall HRQoL using PRO data collected from outpatients in this trial.