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 (preprint)

Purposeto 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. Methodsanti-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. Resultsnon 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. Conclusionabsence / 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 messageabsent 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.

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with High-Flow Nasal Oxygen therapy. A multicenter, adjusted cohort study (preprint)

Background: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods Prospective, multicentre, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June, 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory sequential organ failure assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO+awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95%CI: 0.53–1.43), p=0.60]. Patients treated with HFNO+awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days, (p=0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95%CI: 0.40–2.72), p=0.92]. Conclusion In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

SARS-CoV-2-RNA viremia is associated to hypercytokinemia and critical illness in COVID-19 (preprint)

BackgroundSevere COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues. Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis-like disease observed in severe COVID-19 is currently unknown. MethodsWe determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution. ResultsThe presence of SARS-CoV-2-RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 - 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 - 0.88], <0.001). Conclusionssystemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.