The study is a double-blind, randomised, placebo-controlled trial that will be conducted primarily in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other persons at risk of contracting COVID-19, who can be followed reliably for 5 months. The initial aim was to recruit 40,000 participants and we predict an average of 400-800 participants per site in 50-100 sites.

The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 3 months.

If the participant is diagnosed with COVID-19, they will take continue to take the study medication until:

• 90 days after enrolment (i.e., completion of kit)
• hospitalised due to COVID-19 disease (i.e., not for quarantine purposes) in which case they will stop, or
• advised to stop by their healthcare professional for other reasons

Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.

This study is funded by Wellcome Trust Grant reference 221307/Z/20/Z.

Study Participants The study population is adult healthcare workers and other persons defined by the site investigator at risk of contracting COVID-19.

Inclusion Criteria

1. Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct
2. Agrees not to self-medicate with chloroquine, hydroxychloroquine or other potential antivirals
3. Adults (exact age is dependent on countries) less than 70 years old at the time of consent
4. Not previously diagnosed with COVID-19
5. Not currently symptomatic with an ARI
6. Participant is a healthcare worker or is a person at risk of contracting COVID-19.
7. Possesses an internet-enabled smartphone (Android or iOS)

Exclusion Criteria:

1. Hypersensitivity reaction to chloroquine, hydroxychloroquine or 4-aminoquinolines
2. Contraindication to taking chloroquine as prophylaxis e.g. known epileptic, known creatinine clearance < 10 ml/min
3. Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines, or history of these medications within the previous 7 days
4. Taking prohibited medications
5. Known retinal disease
6. Inability to be followed up for the trial period
7. Known prolonged QT syndrome (however ECG is not required at baseline)
8. Known pregnancy or women who are actively trying to become pregnant
9. Prior diagnosis of porphyria
10. Previously received any dose of COVID-19 vaccine

The investigator may consult the physician's guidance documents for any further questions regarding eligibility of potential participants.

Prohibited medications for the purpose of study enrollment include:

• Antiarrhythmic medications: digoxin, amiodarone, sotalol, flecainide
• Antiparasitic/malarial agents: mefloquine, halofantrine, praziquantel
• Antibiotics: levofloxacin, moxifloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin
• Antifungal drugs: fluconazole, ketoconazole, itraconazole, terfenadine
• Psychoactive drugs: lithium, quetiapine, chlorpromazine, thioridazine, ziprasidone, haloperidol, droperidol, methadone
• Migraine treatment: sumatriptan
• Antihistamines: astemizole
• Antiemetics: prochlorperazine, metoclopramide
• Cancer treatments: abiraterone, dabrafenib, dacomitinib, enzalutamide, idelalisib, mitotane
• Other specific drugs: ciclosporin, conivaptan, agalsidase alfa or beta, mifepristone, stiripentol

PrincipaI Investigators will also be directed to crediblemeds.org to check other agents that may prolong QT interval

With participant's consent, suitably anonymised clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future.