Exploring the Potential of Broadly Neutralizing Antibodies for Treating SARS-CoV-2 Variants of Global Concern in 2023: A Comprehensive Clinical Review.

In the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, the world is still seeing outbreaks of COVID-19 infections as of 2023, especially in populations that have been adequately vaccinated. This situation across the globe gives rise to important questions regarding the efficacy of current treatments and the real rate of mutations in the COVID-19 virus itself which can make the currently available treatments and vaccines obsolete. We have tried to answer a few of those questions and put forth some new questions of our own. Our efforts in this paper were directed towards understanding the utilization of broadly neutralizing antibodies as a treatment for COVID-19 infection with a particular focus on the Omicron variant and other newer variants. We gathered our data from three major databases: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL). We have screened 7070 studies from inception till March 5, 2023, and gathered 63 articles that were relevant to the topic of interest. Based on the existing medical literature regarding the topic of interest and also based on our own personal and clinical experience treating COVID-19 patients across the multiple waves in the United States and India since the beginning of the pandemic, we have concluded that broad neutralizing antibodies could be an effective option for treatment and prophylaxis for current and future outbreaks of COVID-19 including the Omicron variant and newer variants. Further research, including clinical trials, is required to tailor optimal dosages, prevent adverse reactions/side effects, and develop treatment strategies.

Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm).

INTRODUCTION: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein produced in the lung, is essential for pulmonary host defense and alveolar integrity. Prior studies suggest potential benefits in several pulmonary conditions, including acute respiratory distress syndrome and viral infections. This trial evaluated the effect of the addition of inhaled sargramostim (yeast-derived, glycosylated recombinant human GM-CSF) to standard of care (SOC) on oxygenation and clinical outcomes in patients with COVID-19-associated acute hypoxemia. MATERIALS AND METHODS: A randomized, controlled, open-label trial of hospitalized adults with COVID-19-associated hypoxemia (oxygen saturation <93% on ≥2 L/min oxygen supplementation and/or PaO2/FiO2 <350) randomized 2:1 to inhaled sargramostim (125 mcg twice daily for 5 days) plus SOC versus SOC alone. Institutional SOC before and during the study was not limited. Primary outcomes were change in the alveolar-arterial oxygen gradient (P(A-a)O2) by day 6 and the percentage of patients intubated within 14 days. Safety evaluations included treatment-emergent adverse events. Efficacy analyses were based on the modified intent-to-treat population, the subset of the intent-to-treat population that received ≥1 dose of any study treatment (sargramostim and/or SOC). An analysis of covariance approach was used to analyze changes in oxygenation measures. The intubation rate was analyzed using the chi-squared test. All analyses are considered descriptive. The study was institutional review board approved. RESULTS: In total, 122 patients were treated (sargramostim, n = 78; SOC, n = 44). The sargramostim arm experienced greater improvement in P(A-a)O2 by day 6 compared to SOC alone (least squares [LS] mean change from baseline [SE]: -102.3 [19.4] versus -30.5 [26.9] mmHg; LS mean difference: -71.7 [SE 33.2, 95% CI -137.7 to -5.8]; P = .033; n = 96). By day 14, 11.5% (9/78) of sargramostim and 15.9% (7/44) of SOC arms required intubation (P = .49). The 28-day mortality was 11.5% (9/78) and 13.6% (6/44) in the sargramostim and SOC arms, respectively (hazard ratio 0.85; P = .76). Treatment-emergent adverse events occurred in 67.9% (53/78) and 70.5% (31/44) on the sargramostim and SOC arms, respectively. CONCLUSIONS: The addition of inhaled sargramostim to SOC improved P(A-a)O2, a measure of oxygenation, by day 6 in hospitalized patients with COVID-19-associated acute hypoxemia and was well tolerated. Inhaled sargramostim is delivered directly to the lung, minimizing systemic effects, and is simple to administer making it a feasible treatment option in patients in settings where other therapy routes may be difficult. Although proportionally lower rates of intubation and mortality were observed in sargramostim-treated patients, this study was insufficiently powered to demonstrate significant changes in these outcomes. However, the significant improvement in gas exchange with sargramostim shows this inhalational treatment enhances pulmonary efficiency in this severe respiratory illness. These data provide strong support for further evaluation of sargramostim in high-risk patients with COVID-19.

Corrected QT Interval Prolongation, Elevated Troponin, and Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has risen to the level of a global pandemic. Growing evidence has proven the cardiac involvement in SARS-CoV-2 infection. This study aims to evaluate the ability of cardiovascular complications determined by elevated troponin and electrocardiogram findings (e.g., corrected QT interval (QTc)) in predicting the severity of SARS-CoV-2 infection among hospitalized patients. METHODS: This is a retrospective review of medical records of 800 patients, admitted to Richmond University Medical Center in Staten Island, NY, and tested positive for SARS-CoV-2 between March 1, 2020 and July 31, 2020. A total of 339 patients met the study inclusion and exclusion criteria and were included in statistical analysis. RESULTS: Elevated serum troponin levels on admission statistically correlated with mortality in SARS-CoV-2 patients. Prolonged QTc was shown to have an independent statistically significant association with mortality among patients hospitalized with SARS-CoV-2. CONCLUSIONS: Growing concern for cardiovascular sequelae of coronavirus disease 2019 (COVID-19) has prompted many researchers to investigate the role of cardiovascular complications in mortality due to SARS-CoV-2. Obtaining a simple electrocardiogram for hospitalized patients with COVID-19 could provide an independent prognostic tool and prompt more coordinated treatment strategies to prevent mortality among patients hospitalized with COVID-19.

A COVID-19 Case Complicated by Candida dubliniensis and Klebsiella pneumoniae-Carbapenem-Resistant Enterobacteriaceae.

There has been increasing evidence of co-infections with coronavirus disease 2019 (COVID-19) pneumonia, which increases the severity of the disease. Organisms such as Klebsiella pneumoniae and Streptococcus pneumoniae have been previously isolated. We present a case of a COVID-19 patient treated with baricitinib and dexamethasone who later developed Klebsiella pneumoniae-carbapenem-resistant Enterobacteriaceae (CRE) and Candida dubliniensis bloodstream infections, treated with meropenem/vaborbactam and micafungin, respectively. These infections are exceedingly rare and are mostly reported in immunosuppressed patients. The finding of these bloodstream infections raises concerns on the cause of immunosuppression in this patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treated with baricitinib and dexamethasone. There has been no report so far of COVID-19 associated with these co-infections.

A Novel Report on the Compassionate Use of Baricitinib in Treating a Pediatric Patient With Severe Symptoms of COVID-19 Infection.

Since the outbreak of the pandemic coronavirus disease 2019 (COVID-19), there has been an increasing need for treatment to decrease morbidity and mortality of patients presenting with severe disease symptoms. There has been increasing evidence to suggest that the pathophysiological basis is a severe inflammatory response that resembles the cytokine release syndrome. Current strategies to counteract this involve modifiers of the immune response such as interleukin (IL)-6 receptor blockers and Janus kinase (JAK) inhibitors. An example of a JAK inhibitor is baricitinib. In this case, we present a 17-year-old female admitted with severe COVID-19 symptoms, who was placed on high-flow nasal cannula and started on azithromycin and hydroxychloroquine, which were standard of care at the time. Due to the worsening of symptoms, she was given baricitinib for compassionate use. There was a rapid improvement in clinical and imaging findings, and the patient was discharged from the hospital within 8 days of admission. This study is fascinating because there are very limited studies published on the benefits of baricitinib in managing patients with severe symptoms of COVID-19 especially in the pediatric population, and the rapidity in recovery time was remarkable.

COVID-19-Induced Diabetic Ketoacidosis and Acute Respiratory Distress Syndrome in an Obese 24-Year-Old Type I Diabetic.

BACKGROUND In early 2020, severe acute respiratory syndrome-corona virus 2 caused an outbreak of a viral pneumonia that rapidly progressed to a global pandemic. Most cases presented with mild respiratory symptoms and required only supportive care with instructions to self-quarantine at home. Others had more severe symptoms that became complicated by acute respiratory distress syndrome (ARDS) and required hospitalization. CASE REPORT In this report, we present the case of a young patient in New York City who presented to our hospital with coronavirus disease 2019-induced diabetic ketoacidosis (DKA) that progressed to ARDS and subsequent death. The patient was managed for DKA on presentation with insulin protocol and acidosis management. However, it became evident that he had underlying respiratory complications, which later presented as ARDS requiring mechanical ventilation and antibiotics. CONCLUSIONS We recommend that clinicians be aware of this potentially fatal complication in all patients with pre-existing diabetes. Simultaneously, a low threshold for intubation should be advocated for patients with concurrent COVID-19 and type I diabetes mellitus since the potential for poor clinical outcomes from respiratory demise may be lessened by early respiratory intervention.

It's complicated: A case report on a COVID-19-positive HIV patient presenting with rhabdomyolysis and acute kidney injury.

The SARS-Cov-2/COVID-19 pandemic in early 2020 has had a devastating impact on health systems around the world. While viral pneumonia remains the most common complication, reports are surfacing of cases with neurological, cardiac, and renal involvement. Even less is known about the implications in special high-risk populations. In this report, we discuss a unique case of an HIV-positive patient in New York City who presented with a 2-week history of worsening fatigue, cough, dyspnea, and myalgias and was found to have COVID-19 pneumonia and acute kidney injury. He was managed for severe uremic metabolic acidosis and electrolyte abnormalities with emergent hemodialysis and supportive therapy with subsequent improvement. Direct involvement of SARS-CoV-2 and pneumonia-induced rhabdomyolysis were identified as the precipitating factors of his acute kidney injury. The pathophysiologic mechanisms of acute kidney injury, SARS-CoV-2 renal tropism, and the impact of highly active antiretroviral therapy on COVID-19 pneumonia are discussed. We highlight the importance of clinician awareness of this potentially fatal complication of COVID-19 pneumonia, particularly in the HIV-positive population as early recognition and management can have favorable outcomes.

What are we missing? Three cases of severe COVID-19 pneumonia with negative testing.

The COVID-19 pandemic has drastically affected health care systems globally. Reverse transcriptase-polymerase chain reaction is currently the preferred method of detecting COVID-19; however, sensitivity of this test remains questionable. Incidental transmission and potential harm to infected individuals are some consequences of the failure to identify high-risk patients. We report three cases of symptomatic patients that required intensive care management with labs and imaging consistent with COVID-19 with initial false-negative reverse transcriptase-polymerase chain reaction testing. Improper sampling, viral load, and manufacturer variances of tests all contribute to reduced sensitivity. A clinical diagnosis should supplant such cases.

COVID-19: The Case of Three Patients with the Same Diagnosis but Different Clinical and Laboratory Features.

SARS-CoV-2 is an RNA virus that causes COVID-19, which has been responsible for the pandemic that was declared in early 2020. Its pathological effect is majorly in the respiratory tract, but its full pathogenicity remains a mystery. Symptoms associated with COVID-19 include fever, cough, and shortness of breath. Some patients develop other symptoms like diarrhea. However, it is possible for other organs to be affected including the central nervous system, liver, and blood cells. The purpose of this case series is to unravel other factors associated with this disease, so we report three cases of COVID-19 that were hospitalized during the pandemic.