The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study

  1. Tarek Sulaiman
  2. Abdulrhman Mohana
  3. Laila Alawdah
  4. Nagla Mahmoud
  5. Mustafa Hassanein
  6. Tariq Wani
  7. Amel Alfaifi
  8. Eissa Alenazi
  9. Nashwa Radwan
  10. Nasser AlKhalifah
  11. Ehab Elkady
  12. Manwer Alanazi
  13. Mohammed Alqahtani
  14. Khalid Abdullah
  15. Yousif Yousif
  16. Fouad AboGazalah
  17. Fuad Awwad
  18. Khaled Alabdulkareem
  19. Fahad AlGhofaili
  20. Ahmad AlJedai
  21. Hani Jokhdar
  22. Fahad Alrabiah

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Abstract

BACKGROUND

Currently, there is no proven effective therapy nor vaccine for the treatment of SARS-CoV-2. Evidence regarding the potential benefit of early administration of hydroxychloroquine (HCQ) therapy in symptomatic patients with Coronavirus Disease (COVID-19) is not clear.

METHODS

This observational prospective cohort study took place in 238 ambulatory fever clinics in Saudi Arabia, which followed the Ministry of Health (MOH) COVID-19 treatment guideline. This guideline included multiple treatment options for COVID-19 based on the best available evidence at the time, among which was Hydroxychloroquine (HCQ). Patients with confirmed COVD-19 (by reverse transcriptase polymerase chain reaction (PCR) test) who presented to these clinics with mild to moderate symptoms during the period from 5-26 June 2020 were included in this study. Our study looked at those who received HCQ-based therapy along with supportive care (SC) and compared them to patients who received SC alone. The primary outcome was hospital admission within 28-days of presentation. The secondary outcome was a composite of intensive care admission (ICU) and/or mortality during the follow-up period. Outcome data were assessed through a follow-up telephonic questionnaire at day 28 and were further verified with national hospitalisation and mortality registries. Multiple logistic regression model was used to control for prespecified confounders.

RESULTS

Of the 7,892 symptomatic PCR-confirmed COVID-19 patients who visited the ambulatory fever clinics during the study period, 5,541 had verified clinical outcomes at day 28 (1,817 patients in the HCQ group vs 3,724 in the SC group). At baseline, patients who received HCQ therapy were more likely to be males who did not have hypertension or chronic lung disease compared to the SC group. No major differences were noted regarding other comorbid conditions. All patients were presenting with active complaints; however, the HCQ groups had higher rates of symptoms compared to the SC group (fever: 84% vs 66.3, headache: 49.8 vs 37.4, cough: 44.5 vs 35.6, respectively). Early HCQ-based therapy was associated with a lower hospital admission within 28-days compared to SC alone (9.4% compared to 16.6%, RRR 43%, p-value <0.001). The composite outcome of ICU admission and/or mortality at 28-days was also lower in the HCQ group compared to the SC (1.2% compared to 2.6%, RRR 54%, p-value 0.001). Adjusting for age, gender, and major comorbid conditions, a multivariate logistic regression model showed a decrease in the odds of hospitalisation in patients who received HCQ compared to SC alone (adjusted OR 0.57 [95% CI 0.47-0.69], p-value <0.001 ). The composite outcome of ICU admission and/or mortality was also lower for the HCQ group compared to the SC group controlling for potential confounders (adjusted OR 0.55 [95% CI 0.34-0.91], p-value 0.019).

CONCLUSION

Early intervention with HCQ-based therapy in patients with mild to moderate symptoms at presentation is associated with lower adverse clinical outcomes among COVID-19 patients, including hospital admissions, ICU admission, and/or death.

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    SciScore for 10.1101/2020.09.09.20184143: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients who attended these clinics provided consent be enrolled in and allow the use of their clinical data for prospective research purposes at their first visit.
    IRB: Ethical consideration: The Saudi Arabian MOH central Institutional Review Board (IRB) approved this observational prospective cohort study, log number: 20-129M.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Although our study included a large cohort of symptomatic COVID-19 participants, we acknowledge that it has several limitations. The population represented in the dataset analysed is relatively young with a limited number of patients who were above the age of 65 years based on the cautionary measure taken by the national ambulatory fever clinic program. Although the multivariable model adjusts for this age group, given the small numbers of patients in this stratum, we caution from generalising the results to this age-group. Furthermore, the study took place in all regions of the Kingdom during the pandemic, which imposed some logistic challenges leading to losing the follow up of many patients in both treatment groups. To overcome this anticipated challenge, the study protocol was designed with an additional verification process to ensure capturing all hard outcome data from reliable national registries. As this verification process was non-differential to the initial treatment group allocation, and the fact that the sample size of the cohort is considered large, we believe that the overall results are valid.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2020.09.09.20184143v1 on medRxiv