Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study – BMC Infectious Diseases

Study design and data source

This retrospective cohort study followed STROBE and RECORD reporting guidelines. We used data from administrative health datasets managed by Public Health Scotland and National Records of Scotland, linked and pseudonymized by the electronic Data Research and Innovation Service.

The study cohort was drawn from the Scottish general practitioner-registered population living within six health boards (i.e. Ayrshire & Arran, Dumfries & Galloway, Forth Valley, Greater Glasgow & Clyde, Lanarkshire and Lothian) that used the Hospital Electronic Prescribing and Medicines Administration (HEPMA) system for recording administration and prescription of COVID-19 therapies.

The index date (Day 1) was defined as the earliest date of a confirmed COVID-19 diagnosis (via reverse transcriptase polymerase chain reaction [RT-PCR] or lateral flow test [LFT]), or treatment date during the study period. Patients were followed up for 28 days (Day 28) from index (defined as the acute period), during which patient outcomes were evaluated. We included patients diagnosed with COVID-19 from December 1, 2021–October 25, 2022. The baseline period was defined as the 2 years prior to index for secondary care events and 1 year prior to index for general practitioner prescriptions.

Study population

Non-hospitalized patients (defined as having treatment for COVID-19 initiated in an outpatient or community setting) were eligible for inclusion if they were aged ≥ 18 years on the index date; had a COVID-19 diagnosis/positive SARS-CoV-2 RT-PCR or LFT; lived within 1 of the 6 geographical zones attached to a Scottish health board that used the HEPMA prescribing system; met ≥ 1 of the NHS highest-risk conditions criteria for receiving early treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir (as defined by the presence of diagnosis codes) (Table 1); and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir, or molnupiravir, or received no early COVID-19 treatment.

At the time of study, the NHS highest-risk criteria were Down’s syndrome, solid cancer, hematologic diseases (including cancers), advanced renal disease, advanced liver disease, immune-mediated inflammatory disease (IMID), immune deficiencies, HIV/AIDS, solid-organ and stem-cell transplant recipients, and rare neurologic conditions [4]. These highest-risk criteria were evaluated during the baseline period.

Patients were excluded if they received more than one COVID-19 treatment (sotrovimab, nirmatrelvir/ritonavir, molnupiravir, or remdesivir) in an outpatient setting during the acute period. Patients were also excluded if they received remdesivir as an early treatment in an outpatient setting, or initiated any COVID-19 treatment while in an inpatient setting (defined as overnight admission on the day of or prior to treatment, and discharge after the day of treatment). These latter two criteria were intended to ensure that only non-hospitalized patients with mild-to-moderate COVID-19 were included.

Study outcomes

The primary outcomes of this study were the proportions of patients with all-cause and COVID-19-related hospitalizations during the acute period (28 days following index). COVID-19-related hospitalizations were defined as any non-elective hospital visit for which COVID-19 was listed in the primary diagnosis field (among patients in whom the hospitalization episode was complete, i.e. discharge had occurred and clinical coding was complete).

Secondary outcomes included the number of all-cause and COVID-19-related inpatient hospitalization days, the proportion of patients with a critical care admission as part of hospitalization, the proportion of patients requiring non-invasive ventilation and mechanical ventilation, and the proportion of deaths during the acute period.

For all outcomes, patients were excluded if there was less than 45 days between the index diagnosis and data extraction censoring dates (regardless of whether they died in this interval) for the outcomes data (October 6, 2022). Forty-five days is the period recommended by Public Health Scotland to account for a reporting lag in the datasets used.

Patient characteristics were also recorded, including age, sex, COVID-19 vaccination status, and comorbidity history. Cohorts were described in relation to “highest-risk” conditions that made patients eligible for early treatment with sotrovimab, nirmatrelvir/ritonavir, or molnupiravir, as mentioned above. Additionally, the cohorts were described in relation to other “high-risk” conditions that may predispose patients to severe COVID-19 outcomes (Table 1).

Outcomes were reported for the following cohorts: Cohort 1, patients receiving early treatment with sotrovimab; Cohort 2, patients receiving early treatment with nirmatrelvir/ritonavir; Cohort 3, patients receiving early treatment with molnupiravir; and Cohort 4, patients at highest risk who received no early COVID-19 treatment.

A subgroup analysis was also conducted. We described 28-day COVID-19-related hospitalization among sotrovimab-treated patients (Cohort 1) and those without any early COVID-19 treatments (Cohort 4) during the periods of Omicron BA.1 (December 1, 2021–February 28, 2022), Omicron BA.2 (March 1–May 31, 2022) and Omicron BA.5 (June 1–September 30, 2022) subvariant predominance in the UK (Fig. 1) [19]. These analyses were not performed for patients treated with nirmatrelvir/ritonavir or molnupiravir due to small sample sizes. Due to low sequencing rates, periods of most prevalent circulating variants were used as a proxy for the infecting variant.

Data analysis

Continuous variables (e.g. age) were summarized using mean, standard deviation, median, interquartile range, and range. Categorical variables (e.g. sex) were described using frequencies and percentages. Due to the study’s information governance and data suppression rules, counts of between 0 and 5 were suppressed and are reported as n =  ≤ 5 throughout (unless they were structural zeros caused by inclusion/exclusion criteria). This suppression did not apply to mortality data.