Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

BackgroundColchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions. MethodsIn this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus colchicine twice daily for 10 days or until discharge (or one of the other treatment arms) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FindingsBetween 27 November 2020 and 4 March 2021, 5610 patients were randomly allocated to receive colchicine and 5730 patients to receive usual care alone. Overall, 1173 (21%) patients allocated to colchicine and 1190 (21%) patients allocated to usual care died within 28 days (rate ratio 1.01; 95% confidence interval [CI] 0.93-1.10; p=0.77). Consistent results were seen in all pre-specified subgroups of patients. There was no significant difference in duration of hospitalisation (median 10 days vs. 10 days) or the proportion of patients discharged from hospital alive within 28 days (70% vs. 70%; rate ratio 0.98; 95% CI 0.94-1.03; p=0.44). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (25% vs. 25%; risk ratio 1.02; 95% CI 0.96-1.09; p=0.47). InterpretationIn adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056). Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.

Previous COVID-19 infection but not Long-COVID is associated with increased adverse events following BNT162b2/Pfizer vaccination

ImportanceUnderstanding Adverse Events (AEs) associated with SARS-CoV-2 vaccination has public health implications, especially with regards to vaccine hesitancy. ObjectiveTo establish whether individuals with prior history of COVID-19 were more likely to experience AEs after BNT162b2/Pfizer vaccination, than those without previous COVID-19, and whether COVID-19-vaccination interval influenced AE severity. DesignAn observational study explored AEs after vaccination. Participants were invited to complete an electronic survey, capturing self-reported COVID-19 symptoms, PCR/antibody results, and AEs following first dose of BNT162b2/Pfizer vaccine. In a subset where PCR/antibody results could be verified, a sensitivity analysis was conducted. SettingThree North-East England hospital Trusts in the United Kingdom. ParticipantsHealthcare workers formed an opportunistic sample - 265 of 974 reported prior positive SARS-CoV-2 PCR and/or antibody. ExposureAll participants had received their first dose of BNT162b2/Pfizer vaccine. Main Outcomes and MeasuresNature, severity, duration, and onset of self-reported AEs (reported via a modified version of the FDA Toxicity Grading Scale for vaccine-associated AEs), was compared between those with and without a prior history of COVID-19, using 2-way ANCOVA and logistic regression. Effects of age, gender, illness-vaccine interval, and ongoing symptoms ( Long-COVID) on AEs, were also explored. ResultsOf 974 respondents (81% female, mean age 48), 265 (27%) reported previous COVID-19 infection. Within this group (symptoms median 8.9 months pre-vaccination), 30 (11%) complained of Long-COVID. The proportion reporting one moderate/severe symptom was higher in the previous COVID-19 group (56% v 47%, OR=1.5 [95%CI, 1.1-2.0], p=.009), with fever, fatigue, myalgia-arthralgia and lymphadenopathy significantly more common. There was no significant relationship between illness-vaccine interval and symptom composite score (rs=0.09, p=.44). Long-COVID was not associated with worse AEs in comparison to the group without previous COVID-19. In the smaller sensitivity analysis cohort (412 people) similar findings were obtained although only myalgia and arthralgia remained significant. Conclusions and RelevancePrior COVID-19 infection but not ongoing Long-COVID symptoms were associated with an increase in the risk of self-reported adverse events following BNT162b2/Pfizer vaccination. COVID-19 illness-vaccination interval did not significantly influence AEs. This data can support education around vaccine-associated AEs and, through improved understanding, help to combat vaccine hesitancy. Key PointsO_ST_ABSQuestionC_ST_ABSDoes previous COVID-19 infection or Long-COVID increase the frequency of Adverse Events (AEs) following first dose of BNT162b2/Pfizer vaccination? FindingsIn a survey-based observational study, healthcare workers in the United Kingdom reported AEs experienced after their first dose of BNT162b2/Pfizer vaccine. Prior COVID-19 infection, but not Long-COVID, were associated with increased risk of self-reported AEs including lymphadenopathy post-vaccination. Duration since COVID-19 infection did not affect severity of AEs. MeaningOur study can inform education and understanding of AEs associated with COVID-19 vaccination and help to combat vaccine hesitancy.