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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 24% Improvement Relative Risk HCQ for COVID-19  Synolaki et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 312 patients in Greece Lower mortality with HCQ (not stat. sig., p=0.27) c19hcq.org Synolaki et al., medRxiv, September 2020 Favors HCQ Favors control

The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality

Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655
Sep 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments. c19hcq.org
Retrospective 117 patients, 58 HCQ showing lower mortality for HCQ patients.
Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3".
Although the 24% lower mortality is not statistically significant, it is consistent with the significant 25% lower mortality [20‑29%] from meta analysis of the 250 mortality results to date.
risk of death, 23.6% lower, RR 0.76, p = 0.27, treatment 21 of 98 (21.4%), control 60 of 214 (28.0%), NNT 15.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Synolaki et al., 5 Sep 2020, retrospective, Greece, preprint, 20 authors.
This PaperHCQAll
Activin/Follistatin-axis deregulation is independently associated with COVID-19 in-hospital mortality
Evgenia Synolaki, Vasileios Papadopoulos, Georgios Divolis, Efstratios Gavriilidis, Georgia Loli, Arianna Gavriil, Christina Tsigalou, Olga Tsahouridou, Eleni Sertaridou, Petros Rafailidis, Arja Pasternack, Dimitrios T Boumpas, Georgios Germanidis, Olli Ritvos, Simeon Metallidis, Panagiotis Skendros, Dr Paschalis Sideras
doi:10.1101/2020.09.05.20184655
Background: Activins are members of the TGFβ-superfamily implicated in the pathogenesis of several immuno-inflammatory disorders. Based on our previous studies demonstrating that over-expression of Activin-A in murine lung causes pathology sharing key features of COVID-19, we hypothesized that Activins and their natural inhibitor Follistatin might be particularly relevant to COVID-19 pathophysiology. Methods: Activin-A, Activin-B and Follistatin levels were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in three independent centers, and compared with common demographic, clinical and laboratory parameters. Optimal-scaling with ridge-regression was used to screen variables and establish a prediction model. Result: The Activin/Follistatin-axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a novel disease scoring system, adding one point for each of Follistatin>6235pg/ml, Activin-A>591pg/ml, Activin-B>249pg/ml, CRP>10.3mg/dL, LDH>427U/L, Intensive Care Unit (ICU) admission, Neutrophil/Lymphocyte-Ratio>5.6, Years of Age>61, Comorbidities>1 and D-dimers>1097ng/ml, efficiently predicted fatal outcome in an initial cohort (AUC: 0.951±0.032, p<10 -6 ). Two independent cohorts that were used for validation indicated comparable AUC (0.958, p=0.880 and 0.924, p=0.256, respectively). Conclusions: This study unravels strong link between Activin/Follistatin-axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based .
Supplementary Data Study criteria and disease status Inclusion criteria of the study were: a) adult patients (>18 years old), any gender; b) positive SARS-CoV-2 RT-PCR testing in nasopharyngeal swab or BAL; c) hospitalization due to COVID-19, any disease stage; d) Known final disease outcome. Patients without available sample obtained before the 21 st day-of-disease were excluded. Comorbidities considered were diabetes mellitus, arterial hypertension, dyslipidemia, obesity, atrial fibrillation, coronary disease, heart-failure, renal-failure, chronic obstructive pulmonary disease or asthma, immunosuppression (without a record of malignancy), autoimmunity and cancer. The disease-status (DS) of COVID-19 patients was classified based on the adaptation of the Sixth Revised Trial Version of the Novel Coronavirus Pneumonia Diagnosis and Treatment Guidance, as described previously by Hadjadj et al [1] . Specifically, mild cases (DS1) were defined as mild clinical symptoms (fever, myalgia, fatigue, diarrhea) and no sign of pneumonia on thoracic X-Ray or/and CT scan. Moderate cases (DS2) were defined as clinical symptoms associated with dyspnea and radiological findings of pneumonia on thoracic X-Ray or/and CT scan, and requiring a maximum of 3 L/min of oxygen. Severe cases (DS3) were defined as respiratory distress requiring more than 3 L/min of oxygen and no other organ failure. Critical cases (DS4) were defined as respiratory failure requiring mechanical ventilation, shock..
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Late treatment
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