The time to alleviation of targeted COVID-19 symptoms by Day 29 for participants with symptom alleviation, was calculated as symptom alleviation date/time minus first dose date/time. For participants who completed Day 29 of the study or discontinued from the study before Day 29 without symptom alleviation (censored) and without inter-current events, time was calculated as last date/time on which symptom alleviation was assessed minus the first dose date/time or Day 28, whichever occurred first. Symptom alleviation was defined as, all targeted symptoms scored moderate or severe at baseline were scored as mild/none and all targeted symptoms scored mild/none at baseline were scored as none, for at least 48 consecutive hours. Targeted symptoms included: stuffy or runny nose, sore throat, shortness of breath, cough, low energy or tiredness, muscle or body aches, headache, chills or shivering and feeling hot or feverish.

Kaplan-Meier (KM) estimates were used in outcome measure analysis.

The Full Analysis Positive Set (FAPS) included all participants, except from one of the site which did not comply with study rules, who were randomized into the study, have received at least 1 dose of study drug, and were SARS-CoV-2 positive at baseline as confirmed by Cepheid's Xpert Xpress CoV-2/Flu/RSV plus test or SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) test from central lab.

Participants with available data were analyzed.

TEAEs were defined as 1 or both of the following:

• Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.
• Any AEs leading to premature discontinuation of study drug. Percentages were rounded off.

Participants in the Safety Analysis Set were analyzed.

Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days.

Percentages were rounded off.

Participants from the Safety Analysis Set who had available postbaseline data were analyzed.

Percentages were rounded off.

Participants in the Safety Analysis Set were analyzed.

COVID-19 symptom resolution was defined as all targeted symptoms scored as none for at least 48 consecutive hours. The first day of the 48 consecutive hours was considered the date of symptom resolution. The time to COVID-19 symptom resolution was the time (expressed as days) from the first dose date/time to the date/time of symptom resolution.

KM estimates were used in the outcome measure analysis.

Participants in the Full Analysis Positive Set with available data were analyzed.

COVID-19 moderate symptom relapse was defined as having at least 1 symptom being moderate or severe OR at least 2 mild symptoms OR a hospitalization for COVID-19 or death, observed on a day during COVID-19 symptom relapse.

Percentages were rounded off.

Participants in the Full Analysis Positive Set who had short symptom recovery with available data were analyzed.

Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified.

KM estimates were used in the outcome measure analysis. Percentages were rounded off.

Participants in the Full Analysis Positive Set were analyzed.

COVID-19-related hospitalization was defined as ≥ 24 hours of acute care for a reason related to COVID-19, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This included specialized acute medical care units within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution. The date and duration (if there was 1 day difference between the start date and end date) of hospital admission, and primary reason for hospitalization (including if the hospitalization was related to COVID-19) was to be recorded.

Percentages were rounded off.

Participants in the Full Analysis Positive Set were analyzed.

The Virology Analysis Set included all participants, who were randomized into the study, had received at least 1 dose of study drug, and had a baseline SARS-CoV-2 viral load ≥ Lower limit of quantification (LLOQ).

Participants with available data were analyzed.

Time to antigen negativity was defined (in days) as the number of days to the first date of 2 consecutive dates achieving a negative result. Antigen negativity was defined as 2 consecutive negative SARS-CoV-2 rapid antigen test (regardless if there was missing data in between), or negative test at last available sample for participants who completed or discontinued from the study after at least 1 positive antigen test.

The Antigen Analysis Set included all participants, who were randomized into the study, had received at least 1 dose of study drug, and had at least 1 SARS-CoV-2 rapid antigen test positive from Day 1 to Day 5 and SARS-CoV-2 polymerase chain reaction (PCR) positive at baseline per Full Analysis Positive Set.

Viral antigen rebound was defined as any positive SARS-CoV-2 rapid antigen test after antigen negativity.

Percentages were rounded off.

Participants from Antigen Analysis Set with antigen negativity were included.

The Pharmacokinetic (PK) Analysis Set included all randomized participants, who took at least 1 dose of study drug and had at least 1 non-missing concentration value reported by the PK laboratory for GS-441524.

Participants with available data were analyzed.

AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady-state.

The Intensive PK Substudy analysis set included all randomized participants, who took at least 1 dose of study drug, participated in the intensive PK substudy, and had at least 1 non-missing concentration for GS-441524, excluding participants with identified outliers, were analyzed.

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Participants from Intensive PK Substudy Analysis Set excluding participants with identified outliers, were analyzed.

Cmax is defined as the maximum observed plasma concentration of drug.

Participants from Intensive PK Substudy Analysis Set excluding participants with identified outliers, were analyzed.

Symptom relapse means at least 2 consecutive diary entries (regardless of missing data in between) where there was any symptom (regardless of severity) OR a hospitalization for COVID-19 or a death after short symptom recovery.

Percentages were rounded off.

Participants in the Full Analysis Positive Set with available data were analyzed.