Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."

Placebo controlled trial. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment assignment.

There is a substantial number of participants who did not complete the study. There were 18 out of 80 (22.5%) in intervention group and 19 out of 72 (26.4%) in the placebo group. Patients were analysed according to randomization group.

37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
No evidence to support that the results were not bias by missing outcome data.
The missing patients might have different outcomes compared to the patients that remained in the trial.
High proportion of withdrawals without explanation

No detailed information on outcome measurement reported. Medical records were used to measure outcomes that were not self-reported. No patients died during the trial.
Participants and personnel were blinded to the treatment, so differences in the ascertainment of the outcome are unlikely. Ascertainment of mortality considered objective enough.

The primary analysis reported agrees with that of the protocol.
Unlikely that multiple outcome measures or analyses were used since 0 patients died during the trial.

Quote: "Patients were randomized 1:1 to fluvoxamine or matching
placebo capsules. Randomization schedules were generated
that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16
and sex. Treatments were randomly allocated using alternating
block sizes of 2 and 4. Randomization allocation was conducted
via REDCap, which displayed randomization assignment
to the laboratory manager (J.S.), who prepared the
study materials, including the study drug or placebo. All outcome
assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment
assignment."

"Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."
No, placebo controlled trial. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment
assignment.

There is a substantial number of participants who did not complete the study. There were 18 in intervention group and 19 in the placebo group.
Patients were analysed according to randomization group.

37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
No evidence to support that the results were not bias by missing outcome data.
The missing patients might have different outcomes compared to the patients that remained in the trial.
High proportion of the withdrawals had no reason explaining it.
No detailed information on outcome measurement reported. Medical records were used to measure outcomes that were not self-reported. No patients died during the trial.
Participants and personnel were blinded to the treatment, so differences in the ascertainment of the outcome are unlikely. Ascertainment of mortality considered subjective enough.
Participants and personnel were blinded to the treatment, so differences in the ascertainment of the outcome are unlikely.

The primary analysis reported in the paper agrees with that of the protocol.
Unlikely that multiple outcome measures or analyses were used since 0 patients died during the trial.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomization group with intention-to treat analyses.

Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported. No information about measuring mortality are reported. Outcome measurement or ascertainment of the outcome are unlikely to differ between groups for mortality.

Comment: The primary analysis reported in the paper agrees with that of the protocol.
Numerical results are unlikely to be selected from multiple outcome measures or analyses.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomization group with intention-to treat analyses.

Quote: "84 participants stopped fluvoxamine and 64 participants
stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing.
We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported. No information about measuring mortality are reported.
Comment: Outcome measurement or ascertainment of the outcome are unlikely to differ for mortality.

Comment: The primary analysis reported in the paper agrees with that of the protocol.
Comment: Numerical results are unlikely to be selected from multiple outcome measures or analyses.

Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."

All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment. Patients were analyzed according to randomization group.

Although 37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study, the authors performed a senstivity analysis to assess the missing data.

In this case we consider hospitalisation as obejctive enough to allow for an unbiased assessment. Study personnel and participants were blinded to the intervention.

The primary analysis reported in the paper agrees with that of the protocol. Unlikely that multiple outcome measures or analyses were used since 0 patients died during the trial.

No concerns.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomization group with intention-to treat analyses.

Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or
social media applications using video-teleconferencing. We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported. Hospital admission is judged to be objective enough to allow for an unbiased assessment. Outcome measurement or ascertainment of the outcome are unlikely to differ between both groups.

Comment: The primary analysis reported in the publication agrees with that of the protocol.

Numerical results are unlikely to be selected from multiple outcome measures or analyses. Outcomes are sufficiently different and details are reported for each measurement separately.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomisation group with intention-to treat analyses.
Quote: "We assessed time-to-event outcomes
using
Cox proportional hazard models and binary outcomes
using logistic regression."

Quote: "84 participants stopped fluvoxamine and 64 participants
stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3,
4, 5, 7, 10, 14, and 28 in person or via telephone contact or
social media applications using video-teleconferencing.
We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported. Hospital admission is judged to be objective enough to allow for an unbiased assessment.
Comment: Outcome measurement or ascertainment of the outcome are unlikely to differ between both groups.

Comment: The primary analysis reported in the paper agrees with that of the protocol.
Comment: Numerical results are unlikely to be selected from multiple outcome measures or analyses. Outcomes re sufficiently different and details are reported for each measurement separately.

Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."

Placebo controlled trial. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment.

There is a substantial number of participants who did not complete the study. There were 18 out of 80 (22.5%) in the intervention group and 19 out of 72 (26.4%) in the placebo group.
Quote: "the data appeared to be missing at random and no data imputation was conducted"

Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random.

37 study participants did not complete the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
No evidence to support that the results were not bias by missing outcome data.

Outcome data could potentially be missing when participants experienced serious adverse events.

Quote: "Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization."
Comment: This was a remote trial with minimal patient-practitioner contact. (Serious) adverse events were self-reported and not verified by practitioner or medical record. Differences in measurement and ascertainment of the outcome unlikely between groups.

The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study."

Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated
that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted
via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment assignment."

"Participants were well matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."
No, placebo controlled trial. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment assignment.

There is a substantial number of participants who did not complete the study. There were 18 in intervention group and 19 in the placebo group.
Quote: "the data appeared to be missing at random and no data imputation was conducted"

Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random.

37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
No evidence to support that the results were not bias by missing outcome data.
Outcome data could potentially be missing when participants experienced serious adverse events.

The outcomes for the missing observations would have been significantly different from the final participants analysed.
Quote: Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization.
Comment: This was a remote trial with minimal patient-practitioner contact. (Serious) adverse events were self-reported and not verified by practitioner or medical record.
Comment: Differences in measurement and ascertainment of the outcome unlikely.

The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study."

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomization group with intention-to treat analyses.

Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether participants took study medication."; "All serious and non-serious adverse events were reported to study personnel as per local regulatory
requirements."
Comment: The outcomes appears to also be self-reported. Outcome measurement or ascertainment of the outcome are unlikely to differ in both groups.

Comment: The primary analysis reported in the paper agrees with that of the protocol.

Numerical results are unlikely to be selected from multiple outcome measures or analyses.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group."

Comment: Patients were analysed according to randomization group with intention-to treat analyses.
Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing.
We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported.
Comment: Outcome measurement or ascertainment of the outcome are unlikely to differ in both groups.

Comment: The primary analysis reported in the paper agrees with that of the protocol.
Comment: Numerical results are unlikely to be selected from multiple outcome measures or analyses.

Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."

Placebo controlled trial. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment assignment.

Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random.

37 study participants did not finish the study. There were 18 out of 80 (22.5%) in the intervention group and 19 out of 72 (26.4%) in the placebo group. No evidence to support that the results were not bias by missing outcome data. The outcomes for the missing observations would have been significantly different from the final participants analysed.

Quote: "Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization."
Comment: This was a remote trial with minimal patient-practitioner contact. (Serious) adverse events were self-reported and not verified by practitioner or medical record. Differences in measurement and ascertainment of outcome unlikely.

The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study."

Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated
that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted
via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment assignment."

"Participants were well matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."
No, placebo controlled trial. All outcome assessors, investigators, and research staff who were in
contact with participants were blinded to participant treatment
assignment.

There is a substantial number of participants who did not complete the study. There were 18 in intervention group and 19 in the placebo group.
Quote: " the data appeared to be missing at random and no data imputation was conducted"

37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
No evidence to support that the results were not bias by missing outcome data.

The outcomes for the missing observations would have been significantly different from the final participants analysed.
Quote: Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization.
Comment: This was a remote trial with minimal patient-practitioner contact. (Serious) adverse events were self-reported and not verified by practitioner or medical record.
Comment: Differences in measurement and ascertainment of outcome unlikely.

In the protocol it states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study."

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."
Quote: "With respect to covariates of age,
body-mass index, and comorbidities, the groups were generally well balanced."

No, The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group.

Comment: Patients were analysed according to randomization group with intention-to treat analysis.
Quote: "We assessed time-to-event outcomes
using Cox proportional hazard models and binary outcomes using logistic regression."

Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported. Outcome measurement or ascertainment of the outcome are unlikely to differ between both groups.

Comment: The primary analysis reported in the paper agrees with that of the protocol.

Numerical results are unlikely to be selected from multiple outcome measures or analyses.

Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Sites requested randomisation by text message to the pharmacist at the coordinating centre.
This maintained concealment of allocation. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)."

"Participants were well matched in demographic and clinical characteristics."

The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group.

Comment: Patients were analysed according to randomization group with intention-to treat analyses.
Quote: "We assessed time-to-event outcomes
using Cox proportional hazard models and binary outcomes using logistic regression."

Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability."
Comment: Proportions of drop-out are comparable between groups and < 12%. This proportion seems tolerable and is not considered to introduce bias to the results.

Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing.
We collected outcome data irrespective of whether
participants took study medication."
Comment: All outcomes were reported to be self-reported.

Outcome measurement or ascertainment of the outcome are unlikely to differ both groups.

The primary analysis reported in the paper agrees with that of the protocol.

Numerical results are unlikely to be selected from multiple outcome measures or analyses.