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Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience

Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027
Aug 2020  
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Median time to PCR- -21% Improvement Relative Risk HCQ for COVID-19  Saleemi et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 85 patients in Saudi Arabia Slower viral clearance with HCQ (not stat. sig., p=0.05) c19hcq.org Saleemi et al., medRxiv, August 2020 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19hcq.org
Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely.
median time to PCR-, 21.0% higher, relative time 1.21, p < 0.05, treatment 65, control 20.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Saleemi et al., 11 Aug 2020, retrospective, Saudi Arabia, preprint, 5 authors.
This PaperHCQAll
Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real-world experience
Sarfraz Saleemi, Abdulrahman Alrajhi, Mohammed Alhajji, Areej Alfattani, Faisal Albaiz
doi:10.1101/2020.08.05.20151027
Background: The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known. Methods: This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Results: Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18+6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R 2 =0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients >60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild-HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group. Conclusion: Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.
References
Arshad, Kilgore, Chaudhry, Jacobsen, Wang et al., Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19, International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.06.099
Chen, Zhang, Zhu, Associations of clinical characteristics and antiviral drugs with viral RNA clearance in patients with COVID-19 in Guangzhou, China: a retrospective cohort study, doi:10.1101/2020.04.09.20058941
Gautret, Lagier, Parola, Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study, Travel Med Infect Dis, doi:10.1016/j.tmaid.2020.101663
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105949
Gorbalenya, Baker, Baric, The species Severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol, doi:10.1038/s41564-020-0695-z
Huang, Li, Xiao, Pang, Liang et al., Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19, National Science Review, doi:10.1093/nsr/nwaa113
Huang, Tang, Pang, Treating COVID-19 with Chloroquine, J Mol Cell Biol, doi:10.1093/jmcb/mjaa014
Mallat, Hamed, Balkis, Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: a retrospective study, doi:10.1101/2020.04.27.20082180
Meyerowitz, Vannier, Friesen, Rethinking the role of hydroxychloroquine in the treatment of COVID-19, FASEB J, doi:10.1096/fj.202000919
Molina, Delaugerre, Goff, No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection, Med Mal Infect, doi:10.1016/j.medmal.2020.03.006
Tang, Cao, Han, Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial, doi:10.1101/2020.04.10.20060558
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Wölfel, Corman, Guggemos, Virological assessment of hospitalized patients with COVID-2019, Nature, doi:10.1038/s41586-020-2196-x
Xiao, Tong, Gao, Zhu, Zhang et al., Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: A descriptive study, J Clin Virol, doi:10.1016/j.jcv.2020.104346
Yao, Ye, Zhang, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis, doi:10.1093/cid/ciaa237
Zhu, Zhang, Wang, A Novel Coronavirus from Patients with Pneumonia in China, 2019, N Engl J Med, doi:10.1056/NEJMoa2001017
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Eighty-five patients were included in the study, 65 in HCQ ' '(Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from ' 'symptom onset to negative PCR and effect of gender, age and disease severity on time to viral ' 'clearance was ' 'measured.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Median time to ' 'negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, ' '19 days (IQR: 8, Mean 18±6, N=20), <jats:italic>(p</jats:italic> &lt;0.05). Forty-one (63%) ' 'patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate ' 'regression model (F=6.8, <jats:italic>P</jats:italic>&lt;0.002, R<jats:sup>2</jats:sup>=0.20) ' 'shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) ' 'and with every year increase in the age, the time to negative PCR would be delayed by 0.12 ' 'days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on ' 'duration (<jats:italic>p</jats:italic> 0.142 and 0.156 respectively) but older patients ≥60 ' 'year had longer duration compared to patients &lt;60 year of age although ' '<jats:italic>p</jats:italic> value did not reach significance (<jats:italic>p</jats:italic> ' '0.073). Median time to negative PCR in mild- HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was ' 'longer when compared with non-HCQ group <jats:italic>(p</jats:italic> &lt;0.05). On day 28, ' 'all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ ' 'group.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Hydroxychloroquine ' '(HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with ' 'COVID-19 and it is correlated with older age. 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Late treatment
is less effective
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