Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

Background: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

Methods: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents.

Native mitral valve endocarditis due to , an uncommon pathogen.

, a commensal gram-positive rod, is an emerging cause of human disease in individuals with multiple comorbidities and in immunocompromised patient populations. New microbiologic laboratory tests including molecular diagnostics with greater sensitivity to detect pathogens facilitate appropriate clinical diagnosis and treatment to decrease patient morbidity and mortality. Here we report a case of community-acquired infective endocarditis of a native mitral valve in a patient with multiple comorbidities.

Risk of Infections With Long-Term Left Ventricular Assist Device Support.

Unlabelled: The average life expectancy post-left ventricular assist device (LVAD) implantation has significantly increased in recent years. Impaired cellular immunity post-LVAD implantation has been suggested. It is not clear if a prolonged duration of LVAD support will lead to an increase in infections and possibly cause opportunistic infections, as seen in immunocompromised patients.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Effect on SARS-CoV-2 viral load using combination therapy with casirivimab/imdevimab and remdesivir.

Evidence suggests that SARS-CoV-2 viral load is an independent predictor of disease severity and mortality. A 61-year-old woman presented with severe COVID-19 and was treated with casirivimab/imdevimab and remdesivir. Quantitative nasopharyngeal (NP) viral loads were trended throughout the treatment course.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.

Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site).

Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery.

Effectiveness of casirivimab/imdevimab in an intensive care unit patient with acute respiratory failure due to SARS-CoV-2 infection.

Casirivimab/imdevimab, a cocktail of monoclonal antibodies, is currently approved for emergency use in high-risk ambulatory patients with early COVID-19 to reduce risk of hospitalization and/or death from SARS-CoV-2 infection. In the United States, there is no approved monoclonal antibody therapy for patients hospitalized for complications due to acute SARS-CoV-2 infection. We describe here the use of casirivimab/imdevimab in a 52-year-old fully vaccinated, immunocompromised man admitted to the intensive care unit for acute hypoxemic respiratory failure due to SARS-CoV-2 infection.

and cytomegalovirus coinfection in a patient with a transplanted kidney.

Cytomegalovirus is a major opportunistic infection after transplantation with significant morbidity and mortality for solid organ transplant recipients. Unrecognized infection with may result in significant morbidity and mortality in immunocompromised patients. Coinfection with multiple pathogens is possible, leading to diagnostic delays, and may make treatment more challenging.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

Background: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment.

Objective: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high.

Design: Randomized, placebo-controlled trial.

causing a brain abscess.

Actinomycosis is an uncommon, chronic granulomatous disease caused by the filamentous, gram-positive bacterium It causes indolent, painful wound infections commonly presenting with oral-cervicofacial manifestations, but other infections of the chest wall and gastrointestinal and genital tract are also seen. A high level of suspicion is required for diagnosis, as it may be missed or mistaken for malignancy. Severe cases may involve the central nervous system and require surgical intervention.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.

Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA).

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Background/aims: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19.

Screening for SARS-CoV-2 via PCR and serological testing in asymptomatic healthcare workers.

The prevalence and seroconversion rate of SARS-CoV-2 infection among asymptomatic health care workers in the US is unclear. Our study utilized real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing and serological evaluation to detect IgG antibodies specific to SARS-CoV-2 antigens in asymptomatic health care workers. A total of 197 subjects with a mean age of 35 years were recruited into the study.

Acute myocardial infarction secondary to mucormycosis after lung transplantation.

We present a case of a 57-year-old man who underwent bilateral lung transplantation for idiopathic pulmonary fibrosis. His immediately post-operative course was complicated by fever and cardiac arrest. Despite supportive care and broad-spectrum antibiotics, he experienced continued clinical decline.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19.

Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

Background: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.

Methods: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Background: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19.

The dynamic treatment of SARS-CoV-2 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or novel coronavirus disease 2019 (COVID-19) emerged from China in December 2019 and progressed to become a global pandemic. Our understanding of its pathophysiology and potential management was initially extrapolated from previous epidemics of coronaviruses like SARS and MERS. SARS-CoV-2 is asymptomatic or minimally symptomatic in more than 80% of patients and requires no additional management; however, the remaining patients progress to pneumonia and hypoxemia with ranging severity, including a smaller group that requires intensive care unit admission.

lymphadenitis.

is a gram-positive anaerobe that colonizes the human oral cavity. Its pathogenesis involves the disruption of the mucosal membrane, leading to suppuration and subsequent abscess formation, most commonly in the cervicofacial region. The bacteria form masses consisting of aggregates of branching, filamentous bacilli.

Enterovirus-associated hemophagocytic lymphohistiocytosis with multiorgan failure.

Hemophagocytic lymphohistiocytosis is a highly fatal hyperinflammatory syndrome that is increasingly being recognized in adults. It can be primary or secondary in the setting of malignancy, autoimmune disorders, infections, or acquired immune deficiencies. We present a case of a 50-year-old man with enterovirus-associated multiorgan system dysfunction and hemophagocytic lymphohistiocytosis.

Sepsis and Challenging Infections in the Immunosuppressed Patient in the Intensive Care Unit.

In 2017, most intensive care units (ICUs) worldwide are admitting a growing population of immunosuppressed patients. The most common causes of pre-ICU immunosuppression are solid organ transplantation, hematopoietic stem cell transplantation, and infection due to human immunodeficiency virus. In this article, the authors review the most frequent infections that cause critical care illness in each of these 3 immunosuppressed patient populations.