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
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Abstract
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.
Take-home message
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.
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SciScore for 10.1101/2021.03.08.21253121: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Samples were stored at −80°C until quantification of antibodies, viral RNA load and antigenemia evaluation. antigenemia evaluation.suggested: NoneImmunoassay for antibody quantification: a specific immunoassay was developed to quantify anti-SARS-CoV-2 S IgG and IgM antibodies in plasma. anti-SARS-CoV-2 S IgGsuggested: NoneIgMsuggested: NoneThe following day, serum samples were added, and the binding to the S protein was determined by successive incubations with a secondary … SciScore for 10.1101/2021.03.08.21253121: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Samples were stored at −80°C until quantification of antibodies, viral RNA load and antigenemia evaluation. antigenemia evaluation.suggested: NoneImmunoassay for antibody quantification: a specific immunoassay was developed to quantify anti-SARS-CoV-2 S IgG and IgM antibodies in plasma. anti-SARS-CoV-2 S IgGsuggested: NoneIgMsuggested: NoneThe following day, serum samples were added, and the binding to the S protein was determined by successive incubations with a secondary peroxidase-conjugated anti- human IgG or IgM (Jackson Immunoresearch, West Grove, PA, USA) antibody and the OPD substrate (Sigma Aldrich, San Luis, MO, USA). anti- human IgGsuggested: NoneSoftware and Algorithms Sentences Resources The area under the curve (AUC) was calculated by using GraphPad Prism 8.0 (GraphPad Sofware, Inc., San Diego, CA, USA) and the following parameters: Baseline Y=0.1; ignore peaks that are less than 10% of the distance from minimum to maximum Y; all peaks must go above the baseline. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Antigenemia: The presence/absence of N antigen of SARS-CoV-2 in plasma was evaluated by using the Panbio™ COVID-19 Ag Rapid Test Device from Abbott (Chicago, IL, USA). Abbottsuggested: (Abbott, RRID:SCR_010477)SPSS INC, Armonk, NY, U.S.A), and figures were generated using GraphPad Prism 8.0 (GraphPad Software, Inc. SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04457505 Recruiting One Year Follow-ups of Patients Admitted to Spanish Intensiv… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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