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All Studies   Meta Analysis    Recent:   

Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121
Mar 2021  
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Mortality 59% Improvement Relative Risk HCQ for COVID-19  Martin-Vicente et al.  ICU PATIENTS Is very late treatment with HCQ beneficial for COVID-19? Retrospective 92 patients in Spain Lower mortality with HCQ (not stat. sig., p=0.41) c19hcq.org Martin-Vicente et al., medRxiv, March 2021 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 411 studies, recognized in 46 countries.
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4,300+ studies for 75 treatments. c19hcq.org
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
This study is excluded in the after exclusion results of meta analysis: unadjusted results with no group details; treatment or control group size extremely small.
risk of death, 59.3% lower, RR 0.41, p = 0.41, treatment 37 of 91 (40.7%), control 1 of 1 (100.0%), NNT 1.7.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Martin-Vicente et al., 8 Mar 2021, retrospective, Spain, preprint, 38 authors.
This PaperHCQAll
Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients
María Martin-Vicente, Raquel Almansa, Isidoro Martínez, Ana P Tedim, Elena Bustamante, Luis Tamayo, César Aldecoa, José Manuel Gómez, Gloria Renedo, Jose Ángel Berezo, Jamil Antonio Cedeño, Nuria Mamolar, Pablo García Olivares, Rubén Herrán, Ramón Cicuendez, Pedro Enríquez, Alicia Ortega, Noelia Jorge, Amanda De La Fuente, Juan Bustamante-Munguira, María José Muñoz-Gómez, Milagros González-Rivera, Carolina Puertas, Vicente Más, Mónica Vázquez, Felipe Pérez-García, Jesús Rico-Feijoo, Silvia Martín, Anna Motos, Laia Fernandez-Barat, Jose María Eiros, Marta Dominguez-Gil, Ricard Ferrer, Ferrán Barbé, David J Kelvin, Jesús F Bermejo-Martin, Salvador Resino, Antoni Torres
doi:10.1101/2021.03.08.21253121
Purpose: to evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19. Methods: anti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis. Results: non survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia ( 47 .4% vs 22.2%) (p <0.05). Non survivors showed lower concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR (CI95%), p]: [S IgM (AUC ≥60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC ≥237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load (≥ 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load (≥ 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load. Conclusion: absence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality.
Funding: This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 -170357) (DJK) and the "Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS-CoV2, causante del COVID-19", FONDO -COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and finally by the "Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación de proyectos de investigación en enfermedad COVID-19" (GRS COVID 53/A/20) (CA). APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-financed by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript. Consent to participate: Informed consent was obtained orally when clinically possible. In the remaining cases, the informed consent waiver was authorized by the Ethics committee. Consent for publication: not applicable Acknowledgements: we thank the IBSAL and CIBER administrative support to run this study.
References
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Hagman, Hedenstierna, Gille-Johnson, SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: a retrospective cohort study, Clin Infect Dis, doi:10.1093/cid/ciaa1285
Hashem, Algaissi, Almahboub, Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients, Viruses, doi:10.3390/v12121390
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Salazar, Christensen, Graviss, Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG, Am J Pathol, doi:10.1016/j.ajpath.2020.10.008
Veyer, Kernéis, Poulet, Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds light on its potential clinical value, Clin Infect Dis, doi:10.1093/cid/ciaa1196
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The impact of these variables on ' '30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression ' 'analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>non survivors ' 'showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors ' '(26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia ' '(47.4% vs 22.2%) (<jats:italic>p</jats:italic> &lt;0.05). Non survivors showed lower ' 'concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were ' 'associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR ' '(CI95%), <jats:italic>p</jats:italic>]: [S IgM (AUC ≥60): 0.48 (0.24; 0.97), 0.040]; [S IgG ' '(AUC ≥237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral ' 'load (≥ 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load (≥ 3.035 copies/mL): 2.32 ' '(1.16; 4.63), 0.017]. Frequency of antigenemia was &gt;2.5-fold higher in patients with ' 'absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral ' 'RNA load.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>absence / ' 'insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to ' 'poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of ' 'antigenemia, and also to increased 30-day ' 'mortality.</jats:p></jats:sec><jats:sec><jats:title>Take-home ' 'message</jats:title><jats:p>absent or low levels of antibodies against the S protein of ' 'SARS-CoV- 2 at ICU admission is associated to an increased risk of mortality, higher ' 'frequency of antigenemia and higher viral RNA loads in plasma. Profiling anti-SARS-CoV-2 s ' 'antibodies at ICU admission could help to predict outcome and to better identify those ' 'patients potentially deserving replacement treatment with monoclonal or polyclonal ' 'antibodies.</jats:p></jats:sec>', 'DOI': '10.1101/2021.03.08.21253121', 'type': 'posted-content', 'created': {'date-parts': [[2021, 3, 8]], 'date-time': '2021-03-08T19:45:13Z', 'timestamp': 1615232713000}, 'source': 'Crossref', 'is-referenced-by-count': 4, 'title': 'Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher ' 'viral loads in plasma, antigenemia and mortality in COVID-19 patients', 'prefix': '10.1101', 'author': [ {'given': 'María', 'family': 'Martin-Vicente', 'sequence': 'first', 'affiliation': []}, {'given': 'Raquel', 'family': 'Almansa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Isidoro', 'family': 'Martínez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ana P.', 'family': 'Tedim', 'sequence': 'additional', 'affiliation': []}, {'given': 'Elena', 'family': 'Bustamante', 'sequence': 'additional', 'affiliation': []}, {'given': 'Luis', 'family': 'Tamayo', 'sequence': 'additional', 'affiliation': []}, {'given': 'César', 'family': 'Aldecoa', 'sequence': 'additional', 'affiliation': []}, {'given': 'José Manuel', 'family': 'Gómez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gloria', 'family': 'Renedo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jose Ángel', 'family': 'Berezo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jamil Antonio', 'family': 'Cedeño', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nuria', 'family': 'Mamolar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pablo García', 'family': 'Olivares', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rubén', 'family': 'Herrán', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ramón', 'family': 'Cicuendez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pedro', 'family': 'Enríquez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alicia', 'family': 'Ortega', 'sequence': 'additional', 'affiliation': []}, {'given': 'Noelia', 'family': 'Jorge', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amanda', 'family': 'de la Fuente', 'sequence': 'additional', 'affiliation': []}, {'given': 'Juan', 'family': 'Bustamante-Munguira', 'sequence': 'additional', 'affiliation': []}, {'given': 'María José', 'family': 'Muñoz-Gómez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Milagros', 'family': 'González-Rivera', 'sequence': 'additional', 'affiliation': []}, {'given': 'Carolina', 'family': 'Puertas', 'sequence': 'additional', 'affiliation': []}, {'given': 'Vicente', 'family': 'Más', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mónica', 'family': 'Vázquez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Felipe', 'family': 'Pérez-García', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jesús', 'family': 'Rico-Feijoo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Silvia', 'family': 'Martín', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anna', 'family': 'Motos', 'sequence': 'additional', 'affiliation': []}, {'given': 'Laia', 'family': 'Fernandez-Barat', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jose María', 'family': 'Eiros', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marta', 'family': 'Dominguez-Gil', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ricard', 'family': 'Ferrer', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ferrán', 'family': 'Barbé', 'sequence': 'additional', 'affiliation': []}, {'given': 'David J', 'family': 'Kelvin', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jesús F', 'family': 'Bermejo-Martin', 'sequence': 'additional', 'affiliation': []}, {'given': 'Salvador', 'family': 'Resino', 'sequence': 'additional', 'affiliation': []}, {'given': 'Antoni', 'family': 'Torres', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2021031009100300000_2021.03.08.21253121v1.1', 'doi-asserted-by': 'crossref', 'unstructured': 'Deb P , Molla MdMA , Rahman KMS-U (2021) An update to monoclonal ' 'antibody as therapeutic option against COVID-19. 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