Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
Martin Modrák, Paul-Christian Bürkner, Tomáš Sieger, Tomáš Slisz, Martina Vašáková, Grigorij Mesežnikov, Luis Fernando Casas-Mendez, Jaromír Vajter, Jan Táborský, Viktor Kubricht, Daniel Suk, Jan Horejsek, Martin Jedlička, Adriana Mifková, Adam Jaroš, Miroslav Kubiska, Jana Váchalová, Robin Šín, Markéta Veverková, Zbyšek Pospíšil, Julie Vohryzková, Rebeka Pokrievková, Kristián Hrušák, Kristína Christozova, Vianey Leos-Barajas, Karel Fišer, Tomáš Hyánek
doi:10.1101/2020.12.03.20239863
We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. Most patients were admitted during the first wave of the epidemic. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.
Conflict of Interest The authors declare that there is no conflict of interest.
References
Agarwal, Mukherjee, Kumar, Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial). medRxiv,
doi:10.1101/2020.09.03.20187252Beigel, Tomashek, Dodd, Remdesivir for the Treatment of Covid-19 -Final Report, New England Journal of Medicine,
doi:10.1056/NEJMoa2007764Bello-Chavolla, Bahena-López, Ne, Predicting Mortality Due to SARS-CoV-2: A Mechanistic Score Relating Obesity and Diabetes to COVID-19 Outcomes in Mexico, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgaa346Boulware, Pullen, Bangdiwala, A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19, New England Journal of Medicine,
doi:10.1056/NEJMoa2016638Brat, Weber, Gehlenborg, International electronic health recordderived COVID-19 clinical course profiles: the 4CE consortium, npj Digital Medicine,
doi:10.1038/s41746-020-00308-0Cap, Tocilizumab announcement
Castelnuovo, Costanzo, Antinori, 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,
doi:10.1016/j.ejim.2020.08.019Catteau, Dauby, Montourcy, Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants, International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.106144Cg, Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on Lopinavir-Ritonavir
Chen, Nirula, Heller, SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19, N Engl J Med. Published online,
doi:10.1056/NEJMoa2029849Core, R: A Language and Environment for Statistical Computing
Dauby, Van Praet, Vanhomwegen, Veliziotis, Konopnicki et al., Tolerability of favipiravir therapy in critically ill patients with COVID-19: A report of four cases, J Med Virol. Published online
Furtado, Berwanger, Fonseca, Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial, The Lancet,
doi:10.1016/S0140-6736(20)31862-6Hood, Dahly, Wilkinson, Statistical review of Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial, Published online,
doi:10.5281/zenodo.3779933Hood, Goulao, Dahly, Yap, Statistical Review of Remdesivir in Adults with Severe COVID-19: A Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial
Horby, Mafham, Linsell, Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. medRxiv,
doi:10.1101/2020.07.15.20151852Kalil, Patterson, Mehta, Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, N Engl J Med. Published online,
doi:10.1056/NEJMoa2031994Li, Zhang, Hu, Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2020.10044Lou, Liu, Qiu, Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: an Exploratory Randomized, Controlled Trial. medRxiv,
doi:10.1101/2020.04.29.20085761Lu, Hu, Fan, ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China. medRxiv,
doi:10.1101/2020.02.20.20025510Maeda, Obata, Rizk, Kuno, The association of interleukin-6 value, interleukin inhibitors, and outcomes of patients with COVID-19 in New York City, J Med Virol. Published online
Mitja, Ubals, Corbacho, A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease. medRxiv,
doi:10.1101/2020.07.20.20157651Parackova, Zentsova, Bloomfield, Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils' but Impaired Monocytes' and Dendritic Cells' Responsiveness, Cells,
doi:10.3390/cells9102206Rajasingham, Bangdiwala, Nicol, Hydroxychloroquine as preexposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. medRxiv,
doi:10.1101/2020.09.18.20197327Recovery, Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report, New England Journal of Medicine,
doi:10.1056/NEJMoa2021436Robin, Turck, Hainard, pROC: an open-source package for R and S+ to analyze and compare ROC curves, BMC Bioinformatics,
doi:10.1186/1471-2105-12-77Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review, JAMA,
doi:10.1001/jama.2020.6019Shi, Yu, Zhao, Wang, Zhao et al., Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan, Critical Care,
doi:10.1186/s13054-020-2833-7Shrestha, Budhathoki, Khadka, Shah, Pokharel et al., Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis, Virol J,
doi:10.1186/s12985-020-01412-zSiemieniuk, Bartoszko, Ge, Drug treatments for covid-19: living systematic review and network meta-analysis, BMJ,
doi:10.1136/bmj.m2980Skipper, Pastick, Engen, Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19, Annals of Internal Medicine,
doi:10.7326/M20-4207Steegen, Tuerlinckx, Gelman, Vanpaemel, Increasing Transparency Through a Multiverse Analysis, Perspect Psychol Sci,
doi:10.1177/1745691616658637Sterne, Murthy, Diaz, Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis, JAMA. Published online,
doi:10.1001/jama.2020.17023Takahashi, Iwasaki, Watanabe, Case studies of SARS-CoV-2 treated with favipiravir among patients in critical or severe condition, International Journal of Infectious Diseases,
doi:10.1016/j.ijid.2020.08.047Therneau, Grambsch, Modeling Survival Data: Extending the Cox Model
Tobaiqy, Qashqary, Al-Dahery, Therapeutic management of patients with COVID-19: a systematic review, Infection Prevention in Practice,
doi:10.1016/j.infpip.2020.100061Valle, Kim-Schulze, Huang, An inflammatory cytokine signature predicts COVID-19 severity and survival, Nature Medicine,
doi:10.1038/s41591-020-1051-9Wilkinson, Dahly, Statistical Review of Favipiravir Versus Arbidol for COVID-19: A Randomized Clinical Trial
Williams, Storlie, Therneau, Jr, Hannig, A Bayesian Approach to Multistate Hidden Markov Models: Application to Dementia Progression, Journal of the American Statistical Association,
doi:10.1080/01621459.2019.1594831Wynants, Calster, Collins, Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal, BMJ,
doi:10.1136/bmj.m1328
