Effects of Tocilizumab in COVID-19 patients: a cohort study.

BACKGROUND: Due to the lack of proven therapies, we evaluated the effects of early administration of tocilizumab for COVID-19. By inhibition of the IL-6 receptor, tocilizumab may help to mitigate the hyperinflammatory response associated with progressive respiratory failure from SARS-CoV-2. METHODS: A retrospective, observational study was conducted on hospitalized adults who received intravenous tocilizumab for COVID-19 between March 23, 2020 and April 10, 2020. RESULTS: Most patients were male (66.7%), Hispanic (63.3%) or Black (23.3%), with a median age of 54 years. Tocilizumab was administered at a median of 8 days (range 1-21) after initial symptoms and 2 days (range 0-12) after hospital admission. Within 30 days from receiving tocilizumab, 36 patients (60.0%) demonstrated clinical improvement, 9 (15.0%) died, 33 (55.0%) were discharged alive, and 18 (30.0%) remained hospitalized. Successful extubation occurred in 13 out of 29 patients (44.8%). Infectious complications occurred in 16 patients (26.7%) at a median of 10.5 days. After tocilizumab was administered, there was a slight increase in PaO2/FiO2 and an initial reduction in CRP, but this effect was not sustained beyond day 10. CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.

IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells.

Low-dose IL-2 represents an immunotherapy to selectively expand regulatory T cells (Tregs) to promote tolerance in patients with autoimmunity. In this article, we show that a fusion protein (FP) of mouse IL-2 and mouse IL-2Rα (CD25), joined by a noncleavable linker, has greater in vivo efficacy than rIL-2 at Treg expansion and control of autoimmunity. Biochemical and functional studies support a model in which IL-2 interacts with CD25 in the context of this FP in trans to form inactive head-to-tail dimers that slowly dissociate into an active monomer. In vitro, IL-2/CD25 has low sp. act. However, in vivo IL-2/CD25 is long lived to persistently and selectively stimulate Tregs. In female NOD mice, IL-2/CD25 administration increased Tregs within the pancreas and reduced the instance of spontaneous diabetes. Thus, IL-2/CD25 represents a distinct class of IL-2 FPs with the potential for clinical development for use in autoimmunity or other disorders of an overactive immune response.

A Review of Extrapulmonary Tuberculosis.

Mycobacterium tuberculosis is an aerobic, non-spore-forming, non-motile bacillus that causes tuberculosis of both pulmonary and extrapulmonary sites. Though nationwide 66 percent of reported tuberculosis cases occur in foreign-born individuals, these individuals only contributed to 29 percent of the cases in South Dakota in 2015, whereas most of our cases were found in citizens born in the U.S.1 The South Dakota Department of Health also reported 317 cases of latent tuberculosis in South Dakota in 20151, making reactivation tuberculosis a major concern for U.S.-born residents. During the five years spanning 2011-2015, we have seen varying presentations of tuberculosis in South Dakota, many of which included extrapulmonary sites. We report a recent case involving of a 62-year-old Native American female with extrapulmonary tuberculosis cystitis.

Atypical Presentations of Tularemia.

Francisella tularensis is a gram-negative coccobacillus that causes a condition commonly referred to as tularemia. There has been a dramatic increase in tularemia cases reported in South Dakota, many of which were challenging to diagnose due to atypical clinical manifestations. We describe an interesting case of pneumonic tularemia and summarize six similar cases, several of which presented with lung nodules suggestive of malignancy. According to the literature, this is only the third outbreak of pneumonic tularemia reported in the U.S. We believe it is important for clinicians to be aware of the increased incidence of tularemia in the area and to be vigilant in the diagnosis and management of these atypically presenting cases.

Vaccination and the health care worker.

Historically, health care worker vaccination has been a strategy to protect the health care worker from infectious work related risk. This article will discuss the transition to health care worker vaccination as a key patient safety initiative for hospitals and health care systems. As the case is evolving toward mandatory influenza vaccination of health care workers, we have outlined key success factors for a voluntary program in a rural frontier referral hospital. Additionally, pertussis vaccination for health care workers is discussed as to the patient safety aspects of a progressive approach further making the case for value creation on behalf of our patients we have the privilege of providing care.

H1N1 influenza in elderly nursing home residents.

We offer this brief report to inform other nursing home medical directors and attending physicians of a possible change in the profile of persons susceptible to H1N1 influenza. If a significant number of cases appear in older persons, the recommendations for H1N1 vaccination may need to be changed to include the elderly.