The role of Interleukin 6 inhibitors in therapy of severe COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although demographic and clinical parameters such as sex, age, comorbidities, genetic background and various biomarkers have been identified as risk factors, there is an unmet need to predict the risk and onset of severe inflammatory disease leading to poor clinical outcomes. In addition, very few mechanistic biomarkers are available to inform targeted treatment of severe (auto)-inflammatory conditions associated with COVID-19. Calprotectin, also known as S100A8/S100A9, MRP8/14 (Myeloid-Related Protein) or L1, is a heterodimer involved in neutrophil-related inflammatory processes. In COVID-19 patients, calprotectin levels were reported to be associated with poor clinical outcomes such as significantly reduced survival time, especially in patients with severe pulmonary disease. AREAS COVERED: Pubmed was searched using the following keywords: Calprotectin + COVID19, S100A8/A9 + COVID19, S100A8 + COVID-19, S100A9 + COVID-19, MRP8/14 + COVID19; L1 + COVID-19 between May 2020 and 8 March 2021. The results summarized in this review provide supporting evidence and propose future directions that define calprotectin as an important biomarker in COVID-19. EXPERT OPINION: Calprotectin represents a promising serological biomarker for the risk assessment of COVID-19 patients.

https://www.tandfonline.com/doi/pdf/10.1080/1744666X.2021.1905526

Circulating Calprotectin as a Biomarker of COVID-19 Severity.

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial

http://www.thelancet.com/article/S221326002100494X/pdf

https://doi.org/10.1016/j.aca.2022.339777

Evaluation of electropolymerized molecularly imprinted polymers (E-MIPs) on disposable electrodes for detection of SARS-CoV-2 in saliva

Background: Coronavirus disease 2019 (COVID-19) is a novel disease associated with a cytokine-mediated, severe, acute respiratory syndrome. Tocilizumab and lenzilumab are recombinant monoclonal antibodies against IL-6 and granulocyte macrophage colony-stimulating factor, respectively, and have been proposed as a potential treatment for acute, hypoxic respiratory failure associated with COVID-19. Results & methodology: We present the case of a 68-year-old man with COVID-19 who was initially treated with hydroxychloroquine and lenzilumab, but continued to develop hypoxemia, requiring an increase in respiratory support with an associated rise in serum inflammatory markers. He was subsequently treated with tocilizumab with marked clinical improvement and a decrease in acute phase reactants within 48 h. Discussion & conclusion: This case demonstrates the effective use of tocilizumab in the treatment of COVID-19 and suggests the superiority of tocilizumab over lenzilumab in the management of this cytokine-mediated syndrome.

/pdf/case-report-use-of-lenzilumab-and-tocilizumab-for-the-13ukrgblwd.pdf

Case report: use of lenzilumab and tocilizumab for the treatment of coronavirus disease 2019.

To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic.The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames.The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05).The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame. 

https://doi.org/10.1016/j.mayocp.2022.09.005

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations in COVID-19 Pandemic, March – October 2020

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is estimated to have affected 6.2 million people in the United States and 27.5 million people worldwide as of September 9, 2020. On February 2, 2020, the Secretary of the Department of Health and Human Services (HHS) determined that the public health emergency justified the development and emergency use of "in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19" by activating the Emergency Use Authorization (EUA) authority under section 564 of the Federal Food, Drug, and Cosmetic Act. Unfortunately, effective mitigation efforts were thwarted early in the outbreak resulting in an expansion of the initial EUA on February 29, 2020, to improve accessibility to in vitro diagnostic testing. Expectantly, the development and deployment of SARS-CoV-2 testing including RT-PCR expanded rapidly in the weeks following the EUA expansion. These newly developed and approved SARS-CoV-2 RT-PCR tests boast impressive positive and negative agreement rates nearing 100%. Despite the exceptionally high rates of agreement, caution is advised as the RT-PCR tests approved under the COVID-19 EUA are in vitro analyses developed with samples artificially doped with SARS-CoV-2 RNA. These tests therefore do not have clinically applicable sensitivity and specificity because they lack a "gold standard" for diagnosis. Here we present three challenging cases requiring cautious interpretation of the newest generation of RT-PCR molecular detection assays, highlighting the major challenges faced by providers treating patients potentially infected with SARS-CoV-2.

/pdf/the-dynamics-of-sars-cov-2-rt-pcr-testing-31poikc9p0.pdf

The Dynamics of SARS-CoV-2 (RT-PCR) Testing

Here, we report the outcome of an 87-year-old man with permanent non-valvular atrial fibrillation who initially presented with complete heart block and received a single right ventricle lead pacemaker programmed to ventricular demand pacing (VVIR). Over the next 10 months, the patient was readmitted to the hospital four times with recurrent edema, pleural effusions, and ascites. He was diagnosed with new onset systolic heart failure with mid-range (40-49%) ejection fraction and cardiorenal syndrome requiring dialysis. The underlying cause of his presentation was determined to be pacemaker syndrome mediated by new onset severe tricuspid regurgitation. He was treated with reimplantation of a pacemaker with His bundle pacing with subsequent improvement in his cardiac status and renal function. Implantation of dual-chamber pacing (DDDR) or His bundle pacing to achieve a narrow QRS complex over ventricular demand pacemaker is recommended whenever possible to reduce the incidence of pacemaker syndrome and improve patient outcomes.

/pdf/acute-onset-of-heart-failure-and-renal-failure-due-to-2qk8dq6q.pdf

Michael Smerina

Papers

Case report: use of lenzilumab and tocilizumab for the treatment of coronavirus disease 2019.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations in COVID-19 Pandemic, March – October 2020

The Dynamics of SARS-CoV-2 (RT-PCR) Testing

Acute Onset of Heart Failure and Renal Failure Due to Pacemaker Syndrome