Version 1
: Received: 2 May 2020 / Approved: 5 May 2020 / Online: 5 May 2020 (03:32:22 CEST)
Version 2
: Received: 6 May 2020 / Approved: 9 May 2020 / Online: 9 May 2020 (04:45:37 CEST)
How to cite:
Membrillo de Novales, F.J.; Ramírez-Olivencia, G.; Estébanez, M.; de Dios, B.; Herrero, M.D.; Mata, T.; Borobia, A.M.; Gutiérrez, C.; Simón, M.; Ochoa, A.; Martínez, Y.; Aguirre, A.; Alcántara, F.D.A.; Fernández-González, P.; López, E.; Campos, S.; Navarro, M.; Ballester, L.E. Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study. Preprints2020, 2020050057 (doi: 10.20944/preprints202005.0057.v1).
Membrillo de Novales, F.J.; Ramírez-Olivencia, G.; Estébanez, M.; de Dios, B.; Herrero, M.D.; Mata, T.; Borobia, A.M.; Gutiérrez, C.; Simón, M.; Ochoa, A.; Martínez, Y.; Aguirre, A.; Alcántara, F.D.A.; Fernández-González, P.; López, E.; Campos, S.; Navarro, M.; Ballester, L.E. Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study. Preprints 2020, 2020050057 (doi: 10.20944/preprints202005.0057.v1).
Cite as:
Membrillo de Novales, F.J.; Ramírez-Olivencia, G.; Estébanez, M.; de Dios, B.; Herrero, M.D.; Mata, T.; Borobia, A.M.; Gutiérrez, C.; Simón, M.; Ochoa, A.; Martínez, Y.; Aguirre, A.; Alcántara, F.D.A.; Fernández-González, P.; López, E.; Campos, S.; Navarro, M.; Ballester, L.E. Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study. Preprints2020, 2020050057 (doi: 10.20944/preprints202005.0057.v1).
Membrillo de Novales, F.J.; Ramírez-Olivencia, G.; Estébanez, M.; de Dios, B.; Herrero, M.D.; Mata, T.; Borobia, A.M.; Gutiérrez, C.; Simón, M.; Ochoa, A.; Martínez, Y.; Aguirre, A.; Alcántara, F.D.A.; Fernández-González, P.; López, E.; Campos, S.; Navarro, M.; Ballester, L.E. Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study. Preprints 2020, 2020050057 (doi: 10.20944/preprints202005.0057.v1).
Abstract
Background: There is no treatment proven effective against COVID-19. Several drugs with in vitro potential against SARS-CoV-2 virus have been proposed. Hydroxychloroquine has in vitro anti-viral and immunomodulatory activity, but there is no current clinical evidence of its effectiveness changing the outcome of the disease. Methods: We enrolled all 18-85 years old inpatients from Central Defense Hospital “Gómez Ulla”, Madrid, Spain, who were hospitalised for COVID-19 and had a definitive outcome (dead or discharged). We used a statistical survival analysis to detect treatment differences associated with in-hospital death. Results: We analysed first 220 medical records. 166 patients met the inclusion criteria. 48,8 % of patients not treated with HCQ died, 22% of those treated with hydroxychloroquine (p=0,002). According to clinical picture at admission, hydroxychloroquine increased the mean cumulative survival in all groups from 1,4 to 1,8 times. This difference was statistically significant in the mild group. Conclusions: in a cohort of 166 patients from 18 to 85 years hospitalised with COVID-19, hydroxychloroquine treatment with 800mg added loading dose increased survival when patients were admitted in early stages of the disease. There was a non-statistically significant trend towards survival in all groups, which will have to be clarified in subsequent studies.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
12 May 2020
Commenter: Frank Conijn
The commenter has declared there is no conflict of interests.
Comment:
Table 2 shows that the D dimer levels at baseline were 558 (HCQ group) versus 1511 (no HCQ group). That is an extreme difference: 558 is quite normal while 1511 is sky-high. How can that have gotten a p value of 0.168? If it's clinically utterly significant, how can it be statistically insignificant?
For those who don't know: D dimer is a biomarker that indicates the risk of thrombosis. And there are more and more reports by clinicians who see all kinds of embolisms in Covid patients on the ICUs.
Received:
12 May 2020
Commenter: Frank Conijn
The commenter has declared there is no conflict of interests.
Comment:
Actually, D-dimer is a protein fragment that's released when a clot dissolves. So it in fact indicates that thrombosis is already occurring. And high levels of D-dimer appear to be a powerful predictor of mortality in hospitalized patients with Covid-19. See https://www.nature.com/articles/d41586-020-01403-8.
Response 2 to
Comment 1
Received:
13 May 2020
Commenter: Frank Conijn
The commenter has declared there is no conflict of interests.
Received:
12 May 2020
Commenter: Francisco Javier Membrillo
The commenter has declared there is no conflict of interests.
Comment:
This point is discussed on V2. At the beginning of the pandemic our ER department didn't perform d-dymer at admission, so we most patients didn't have this data and it's interpretation is difficult. Thanks for the feedback
Received:
12 May 2020
Commenter: Francisco Javier Membrillo
The commenter has declared there is no conflict of interests.
Comment:
Totally agree. Unfortunately, at the beginning of the pandemic in Spain our Emergency department didn't test d-dymer systematically. So over half of patients dont' have this data fullfilled. Please revise v2 were we added a paragraph explaining this point. Thanks for the feedback
Francisco Javier Membrillo de Novales
*
,
Commenter:
The commenter has declared there is no conflict of interests.
For those who don't know: D dimer is a biomarker that indicates the risk of thrombosis. And there are more and more reports by clinicians who see all kinds of embolisms in Covid patients on the ICUs.
Commenter:
The commenter has declared there is no conflict of interests.
Commenter:
The commenter has declared there is no conflict of interests.
Commenter:
The commenter has declared there is no conflict of interests.
Commenter:
The commenter has declared there is no conflict of interests.