Pandemic Science, Reinfections and hydroxychloroquine

2 European reinfections

Netherlands

Marion Koopmans (virologist)

Viral genomes were different

Older person with a weakened immune system

Reinfections had been expected.

We have to see whether it happens often

Belgium

Woman, first time in March, second time in June

Marc Van Ranst (virologist)

Woman’s symptoms relatively mild

May not have created enough antibodies to prevent a reinfection

They might have helped limit the sickness

I think that in the coming days that we will see other similar stories

It’s not good news

How common

High levels of surveillance

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study (European Journal of Internal Medicine,

Immunomodulatory

Anti-inflammatory

Anti-thrombotic

Directly inhibits viral entry and spread in several in vitro and in vivo models

Might inhibit ACE 2, reduced internalization of the virus

)303356/fulltext

Multicenter Italian collaboration, relationship between HCQ therapy and COVID-19 in-hospital mortality

Methods

Retrospective observational study

N = 3,451

33 clinical centers in Italy

February 19th to May 23rd

Laboratory-confirmed SARS-CoV-2 infection

Comparing patients who received HCQ with patients who did not

Dose

HCQ, all centres, 400 mg/day

One centre, 600 mg/day

5 to 15 days

Dose, BNF link

Results

Out of 3,451

76.3% received HCQ

HCQ group

N = 2633

Death rate 8.9

Per, 1,000 person days

Non HCQ group

N = 817

Death rate 15.7

After adjustment for propensity scores

30% lower risk of death in patients receiving HCQ

HR=0.70;

95%CI: 0.59 to 0.84;

HCQ use was associated with a 30% reduced death rate

95%CI: 16% to 41%

These data do not discourage the use of HCQ in inpatients with COVID-19

Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis (26 August, Clinical Microbiology and Infection, France)

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839 articles

29 articles met our inclusion criteria

Including 3 RCTs

Evaluated the effects of hydroxychloroquine with or without azithromycin (except one)

Meta-analysis

Hydroxychloroquine group

n = 11,932 participants for the,

Association with mortality

RR = 0.83 (not significant)

Hydroxychloroquine with azithromycin group

N = 8081

RR = 1.27

Increased risk or mortality

We identified a significant absolute risk difference of +7%

Control group

N = 12,930

Conclusion

Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients

the combination of hydroxychloroquine and azithromycin significantly increased mortality

WHO, Solidarity clinical trial for COVID-19 treatments

On 4 July 2020, WHO accepted the recommendation from the Solidarity Trial’s International Steering Committee to discontinue the trial’s hydroxychloroquine and lopinavir/ritonavir arms.

WHO dose in Solidarity trial

Canadian arm

Treatments for COVID-19: Canadian Arm of the SOLIDARITY Trial (CATCO)

Hydroxychloroquine 800mg BID for 1 day

then 400mg BID for 10 days plus optimized supportive care,

Lancet, retracted paper

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We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study (lancet 21st august

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Retrospective, multinational, cohort

N = 956 374

Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis

Long term it appears to be associated with excess cardiovascular mortality

The addition of azithromycin increases the risk of heart failure and cardiovascular mortality

even in the short term.

We call for careful consideration of the benefit–risk trade-off when counselling those on hydroxychloroquine treatment.