Background Respiratory failure in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection appears related to cytokine release syndrome (CRS) that often results in mechanical ventilation (MV). We investigated the role of tocilizumab (TCZ) on interleukin‐6 (IL‐6) trends and MV in SARS‐CoV‐2 patients. Methods In this longitudinal observational study, 112 patients were evaluated from 2/1/2020 ‐ 5/31/2020. TCZ was administered followed by methylprednisolone to patients with > 3L oxygen (O2) requirement and pneumonia severity index (PSI) score ≤ 130 with CT scan changes. IL‐6, C‐reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D‐dimer, and procalcitonin were monitored on days 0, 3, and 6 of therapy. Statistical analyses were performed with significance ≤ 0.05. Results 80/112 SARS‐CoV‐2‐positive patients (45 males, 56.96%; 34 females, 43.04%) were included in this study. Seven patients expired (8.75%) and nine patients required MV (11.25%). Median IL‐6 levels pre‐administration of TCZ was 342.50 (78.25 ‐ 666.25) pg/mL compared to post‐administration on day 3 (563; 162 ‐ 783) pg/mL ( P < 0.00001). On day 6, the median dropped to 545 (333.50 ‐ 678.50) pg/mL compared to day 3 ( P = 0.709). CRP, ferritin, LDH, and D‐dimer levels were reduced following TCZ therapy. Conclusions Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D‐dimer levels. The sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. IL‐6 levels may be helpful as a prognostic tool. This article is protected by copyright. All rights reserved.

Background Recent literature suggests that approximately 5‐18% of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may progress rapidly to a severe form of the illness and subsequent death. We examined the relationship between sociodemographic, clinical, and laboratory findings with mortality among patients. Methods In this study, 112 patients were evaluated from February‐May 2020 and 80 patients met the inclusion criteria. Tocilizumab (TCZ) was administered, followed by methylprednisolone to patients with pneumonia severity index (PSI) score ≤ 130 and CT scan changes. Demographic data and clinical outcomes were collected. Laboratory biomarkers were monitored during hospitalization. Statistical analyses were performed with significance p≤ 0.05. Results Eighty (80) patients: 45 males (56.25%) and 35 females (43.75%) met the study inclusion criteria. Seven patients (8.75%) were deceased. An increase in mortality outcome was statistically significantly associated with higher average levels of IL‐6 with P value (0.050), and D‐dimer with P value (0.024). Bivariate logistics regression demonstrated a significant increased odds for mortality for patients with bacterial lung infections (OR: 10.83, 95% CI: 2.05 – 57.40, P=0.005 ) and multi‐organ damage (OR: 103.50, 95% CI: 9.92 – 1079.55, P=0.001 ). Multivariate logistics regression showed a statistically significant association for multi‐organ damage (AOR: 94.17, 95% CI: 7.39 ‐ 1200.78, P=0.001 ). Conclusions We identified three main predictors for high mortality. These include interleukin‐6 (IL‐6), D‐dimer, and multi‐organ damage. The latter was the highest potential risk for in‐hospital deaths. This warrants aggressive health measures for early recognition of the problem and initiation of treatment to reverse injuries. This article is protected by copyright. All rights reserved.

Background: Rapid administration of appropriately indicated antibiotics is crucial in septic patients. Sepsis data supports that there is a higher risk of mortality for each hour delay from triage to antibiotic therapy, as well as for inappropriate antibiotic selection. There are a variety of rapid microbial detection systems, such as VERIGENE®, used in acute care facilities to rapidly detect bacteremia and identify resistance markers. Our study investigates the usefulness of VERIGENE® assays in accurately detecting Gram-positive and Gram-negative pathogens when compared to traditional blood culture analysis systems, such as VITEK®. Methods: 819 Gram-positive and 373 Gram-negative blood samples were collected and tested using both VERIGENE® and VITEK®. Statistical tests were two-tailed and observations were defined as statistically significant if P ≤ 0.05. Results: VERIGENE® detected a pathogen in 816/819 (99.6%) samples of the Gram-positive blood cultures and 367/373 (98.3%) samples of the Gram-negatives compared to 805/819 (98.3%) and 367/373 (98.4%), respectively, using VITEK®. Gram-positive cultures had a sensitivity of 99.5% and a specificity of 27.3% (PPV 99.0%, NPV 42.9%, 98.7% accuracy) with VERIGENE analysis. Gram-negatives had a sensitivity of 99.2% and a specificity of 20.0% (PPV 98.9%, NPV 25.0%, 98.4% accuracy). Conclusions: Although statistically insignificant (P = 0.25), VERIGENE® was 1.3% more likely to identify Gram-positive bacteria when compared to conventional methods. Overall, we concluded that VERIGENE® assays are valuable in their ability to rapidly detect microorganisms and resistance markers, given their high sensitivities. This allows for select targeted therapy in patients with sepsis and can ultimately reduce mortality rates.

It is increasingly recognized that intracellular cell signaling is dependent on the spatial organization of signaling molecules. We previously introduced a platform for investigating spatially-dependent signaling, in the context of the immune synapse, a small (~70 square micrometer) region of contact between

Background The severity of respiratory failure in SARS-CoV-2 infection appears to be related to cytokine release syndrome (CRS), resulting in mechanical ventilation (MV). In this observational study, we investigated tocilizumab’s role in the treatment of SARS-CoV-2 and the use of interleukin-6 (IL-6) levels in the management of these patients. Methods Patients with positive SARS-CoV-2 PCR were prospectively observed from February 1, 2020 to May 31, 2020. Data on demographics, medical history, and clinical outcomes were collected. Tocilizumab (TCZ) 4 mg/kg/day q12h was given for 24 hours, followed by methylprednisolone 60 mg q8h for 72 hours to patients with oxygen requirement of 3 L and above. IL-6, C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimers were monitored on days: 0, 3, and 6 following the initiation of therapy. Statistical analyses were performed using a Wilcoxon signed-rank test with significance (α) less than or equal to 0.05 (P ≤ 0.05). Results A total of eighty patients (45 males, 56.96%) and (34 females, 43.04%) with positive SARS-CoV-2 PCR were included in this study. The median age was 63 (51 - 72) years. Seven patients expired (8.75%), and nine patients required mechanical ventilation (11.25%). The median of IL-6 levels before administration of TCZ was 342.50 (78.25 – 666.25) pg/mL compared to after administration of TCZ on day 3, 563 (162-783) pg/mL (P &lt; 0.00001). On day 6, the median dropped to 545 (333.50 - 678.50) pg/mL as compared to day 3 (P = 0.709). Moreover, CRP, ferritin, LDH, and D-dimers levels were reduced following the administration of TCZ. TABLE 1: IL-6 of SARS-CoV-2 patients at before and after Tocilizumab treatment TABLE 2: Laboratory findings of SARS-CoV-2 patients at before and after Tocilizumab treatment Conclusion Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D-dimer levels, which may be useful inflammatory indices in the management of SARS-CoV-2 patients. Furthermore, the sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. The use of IL-6 levels may be helpful as a prognostic tool and in the management of acutely ill SARS-CoV-2 patients. Disclosures All Authors: No reported disclosures