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

DOI record: { "DOI": "10.1101/2021.03.08.21253121", "URL": "http://dx.doi.org/10.1101/2021.03.08.21253121", "abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</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>", "accepted": { "date-parts": [ [ 2021, 3, 8 ] ] }, "author": [ { "affiliation": [], "family": "Martin-Vicente", "given": "María", "sequence": "first" }, { "affiliation": [], "family": "Almansa", "given": "Raquel", "sequence": "additional" }, { "affiliation": [], "family": "Martínez", "given": "Isidoro", "sequence": "additional" }, { "affiliation": [], "family": "Tedim", "given": "Ana P.", "sequence": "additional" }, { "affiliation": [], "family": "Bustamante", "given": "Elena", "sequence": "additional" }, { "affiliation": [], "family": "Tamayo", "given": "Luis", "sequence": "additional" }, { "affiliation": [], "family": "Aldecoa", "given": "César", "sequence": "additional" }, { "affiliation": [], "family": "Gómez", "given": "José Manuel", "sequence": 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monoclonal antibody as therapeutic option against COVID-19. Biosaf Health. https://doi.org/10.1016/j.bsheal.2021.02.001" }, { "DOI": "10.1126/sciimmunol.abe0240", "doi-asserted-by": "crossref", "key": "2021031009100300000_2021.03.08.21253121v1.2", "unstructured": "Röltgen K , Powell AE , Wirz OF , et al (2020) Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci Immunol 5:. https://doi.org/10.1126/sciimmunol.abe0240" }, { "DOI": "10.1186/s13054-020-03398-0", "doi-asserted-by": "publisher", "key": "2021031009100300000_2021.03.08.21253121v1.3" }, { "DOI": "10.1093/cid/ciaa1196", "doi-asserted-by": "crossref", "key": "2021031009100300000_2021.03.08.21253121v1.4", "unstructured": "Veyer D , Kernéis S , Poulet G , et al (2020) Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds light on its potential clinical value. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa1196" }, { "DOI": "10.1093/cid/ciaa1285", "doi-asserted-by": "crossref", "key": "2021031009100300000_2021.03.08.21253121v1.5", "unstructured": "Hagman K , Hedenstierna M , Gille-Johnson P , et al (2020) SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: a retrospective cohort study. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa1285" }, { "DOI": "10.1093/clinchem/hvaa213", "doi-asserted-by": "crossref", "key": "2021031009100300000_2021.03.08.21253121v1.6", "unstructured": "Ogata AF , Maley AM , Wu C , et al (2020) Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease. Clin Chem. https://doi.org/10.1093/clinchem/hvaa213" }, { "key": "2021031009100300000_2021.03.08.21253121v1.7", "unstructured": "CDC (2020) Information for Laboratories about Coronavirus (COVID-19). 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Viruses 12:. https://doi.org/10.3390/v12121390" }, { "DOI": "10.1186/s13054-020-03362-y", "article-title": "Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care", "doi-asserted-by": "crossref", "first-page": "639", "journal-title": "Critical Care", "key": "2021031009100300000_2021.03.08.21253121v1.12", "volume": "24", "year": "2020" }, { "DOI": "10.1007/s12026-020-09137-5", "article-title": "COVID 19: a clue from innate immunity", "doi-asserted-by": "crossref", "first-page": "161", "journal-title": "Immunol Res", "key": "2021031009100300000_2021.03.08.21253121v1.13", "volume": "68", "year": "2020" }, { "DOI": "10.1016/j.cmi.2020.11.025", "doi-asserted-by": "crossref", "key": "2021031009100300000_2021.03.08.21253121v1.14", "unstructured": "Hingrat QL , Visseaux B , Laouenan C , et al (2020) Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives. 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