Pandemic Response Requires Research Samples: A U.S. Safety-Net Hospital's Experience and Call for National Action.

Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts.

INTRODUCTION: End-stage kidney disease (ESKD) patients are at a high risk for Coronavirus Disease 2019 (COVID-19). In this study, we compared characteristics and outcomes of ESKD and non-ESKD patients admitted with COVID-19 to a large safety-net hospital. METHODS: We evaluated 759 adults (45 with ESKD) hospitalized with COVID-19 in Spring of 2020. We examined clinical characteristics, laboratory measures and clinical outcomes. Logistic regression analyses were performed to investigate the associations between ESKD status and outcomes. RESULTS: 73% of ESKD and 47% of non-ESKD patients identified as Black (p = 0.002). ESKD patients were older and had higher rates of comorbidities. Admission ferritin was approximately 6-fold higher in ESKD patients. During hospitalization, the rise in white blood cell count, lactate dehydrogenase, ferritin and C-reactive protein, and the decrease in platelet count and serum albumin were all significantly greater in ESKD patients. The in-hospital mortality was higher for ESKD [18% vs. 10%; multivariable adjusted odds ratio 1.5 (95% CI, 0.48-4.70)], but this did not reach statistical significance. CONCLUSIONS: Among hospitalized COVID-19 patients, ESKD patients had more co-morbidities and more robust inflammatory response than non-ESKD patients. The odds ratio point estimate for death was higher in ESKD patients, but the difference did not reach statistical significance.

Novel ELISA Protocol Links Pre-Existing SARS-CoV-2 Reactive Antibodies With Endemic Coronavirus Immunity and Age and Reveals Improved Serologic Identification of Acute COVID-19 via Multi-Parameter Detection.

The COVID-19 pandemic has drastically impacted work, economy, and way of life. Sensitive measurement of SARS-CoV-2 specific antibodies would provide new insight into pre-existing immunity, virus transmission dynamics, and the nuances of SARS-CoV-2 pathogenesis. To date, existing SARS-CoV-2 serology tests have limited utility due to insufficient reliable detection of antibody levels lower than what is typically present after several days of symptoms. To measure lower quantities of SARS-CoV-2 IgM, IgG, and IgA with higher resolution than existing assays, we developed a new ELISA protocol with a distinct plate washing procedure and timed plate development via use of a standard curve. Very low optical densities from samples added to buffer coated wells at as low as a 1:5 dilution are reported using this 'BU ELISA' method. Use of this method revealed circulating SARS-CoV-2 receptor binding domain (RBD) and nucleocapsid protein (N) reactive antibodies (IgG, IgM, and/or IgA) in 44 and 100 percent of pre-pandemic subjects, respectively, and the magnitude of these antibodies tracked with antibody levels of analogous viral proteins from endemic coronavirus (eCoV) strains. The disease status (HIV, SLE) of unexposed subjects was not linked with SARS-CoV-2 reactive antibody levels; however, quantities were significantly lower in subjects over 70 years of age compared with younger counterparts. Also, we measured SARS-CoV-2 RBD- and N- specific IgM, IgG, and IgA antibodies from 29 SARS-CoV-2 infected individuals at varying disease states, including 10 acute COVID-19 hospitalized subjects with negative serology results by the EUA approved Abbott IgG chemiluminescent microparticle immunoassay. Measurements of SARS-CoV-2 RBD- and N- specific IgM, IgG, IgA levels measured by the BU ELISA revealed higher signal from 9 of the 10 Abbott test negative COVID-19 subjects than all pre-pandemic samples for at least one antibody specificity/isotype, implicating improved serologic identification of SARS-CoV-2 infection via multi-parameter, high sensitive antibody detection. We propose that this improved ELISA protocol, which is straightforward to perform, low cost, and uses readily available commercial reagents, is a useful tool to elucidate new information about SARS-CoV-2 infection and immunity and has promising implications for improved detection of all analytes measurable by this platform.

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).

Early administration of interleukin-6 inhibitors for patients with severe COVID-19 disease is associated with decreased intubation, reduced mortality, and increased discharge.

OBJECTIVE: The aim of this observational study was to determine the optimal timing of interleukin-6 receptor inhibitor (IL6ri) administration for coronavirus disease 2019 (COVID-19). METHODS: Patients with COVID-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into two groups: those requiring ≤45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. The main outcomes were all-cause mortality, discharge alive from hospital, and extubation. RESULTS: A total of 255 COVID-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than those treated in stage III (adjusted hazard ratio (aHR) 0.24, 95% confidence interval (CI) 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR 1.43, 95% CI 1.06-1.93) and were less likely to be intubated (aHR 0.43, 95% CI 0.24-0.79). CONCLUSIONS: IL6ri administration prior to >45% FiO2 requirement was associated with improved COVID-19 outcomes. This can guide clinical management pending results from randomized controlled trials.