Thoracic Ultrasound in COVID-19: Use of Lung and Diaphragm Ultrasound in Evaluating Dyspnea in Survivors of Acute Respiratory Distress Syndrome from COVID-19 Pneumonia in a Post-ICU Clinic.

INTRODUCTION: Dyspnea is a common symptom in survivors of severe COVID-19 pneumonia. While frequently employed in hospital settings, the use of point-of-care ultrasound in ambulatory clinics for dyspnea evaluation has rarely been explored. We aimed to determine how lung ultrasound score (LUS) and inspiratory diaphragm excursion (DE) correlate with patient-reported dyspnea during a 6-min walk test (6MWT) in survivors of COVID-19 acute respiratory distress syndrome (ARDS). We hypothesize higher LUS and lower DE will correlate with dyspnea severity. STUDY DESIGN AND METHODS: Single-center cross-sectional study of survivors of critically ill COVID-19 pneumonia (requiring high-flow nasal cannula, invasive, or non-invasive mechanical ventilation) seen in our Post-ICU clinic. All patients underwent standardized scanning protocols to compute LUS and DE. Pearson correlations were performed to detect an association between LUS and DE with dyspnea at rest and exertion during 6MWT. RESULTS: We enrolled 45 patients. Average age was 61.5 years (57.7% male), with average BMI of 32.3 Higher LUS correlated significantly with dyspnea, at rest (r = + 0.41, p = < 0.01) and at exertion (r = + 0.40, p = < 0.01). Higher LUS correlated significantly with lower oxygen saturation during 6MWT (r = -0.55, p = < 0.01) and lower 6MWT distance (r = -0.44, p = < 0.01). DE correlated significantly with 6MWT distance but did not correlate with dyspnea at rest or exertion. CONCLUSION: Higher LUS correlated significantly with patient-reported dyspnea at rest and exertion. Higher LUS significantly correlated with more exertional oxygen desaturation during 6MWT and lower 6MWT distance. DE did not correlate with dyspnea.

The Evolution of Cardiovascular Ultrasound: A Review of Cardiac Point-of-Care Ultrasound (POCUS) Across Specialties.

The use of cardiac point-of-care ultrasound (POCUS) is now widespread in clinics, emergency departments, and all areas of the hospital. Users include medical trainees, advanced practice practitioners, and attending physicians in many specialties and sub-specialties. Opportunities to learn cardiac POCUS and requirements for training vary across specialties, as does the scope of the cardiac POCUS examination. In this review, we describe both a brief history of how cardiac POCUS emerged from echocardiography and the state of the art across a variety of medical fields.

A Non-Resolving "Hematoma" Diagnosed as an Arteriovenous Malformation by POCUS.

Point-of-care ultrasound (POCUS) is a useful tool for the evaluation of soft tissue masses. We present the case of a patient with a mass on his forehead initially thought to be a slowly resolving hematoma. POCUS examination of the mass revealed a vascular structure more consistent with a post-traumatic arteriovenous malformation (AVM). This case illustrates how POCUS can be utilized to rapidly assess soft tissue masses and even identify unexpected vascularity.

The Use of Point-of-Care Ultrasound (POCUS) in the Diagnosis of Deep Vein Thrombosis.

Acute lower extremity proximal deep venous thrombosis (DVT) requires accurate diagnosis and treatment in order to prevent embolization and other complications. Point-of-care ultrasound (POCUS), a clinician performed, and clinician interpreted bedside ultrasound examination has been increasingly used for DVT evaluation mainly in the urgent and critical care setting, but also in the ambulatory clinics and the medical wards. Studies have demonstrated that POCUS has excellent diagnostic accuracy for acute proximal DVT when performed by well-trained users. However, there is significant heterogeneity among studies on the necessary extent of training and universally acceptable standardized education protocols are needed. In this review, we summarize the evidence that supports the use of POCUS to diagnose acute proximal DVT and focus on methodology and current technology, sensitivity and specificity, pre-test probability and the role of D-dimer, time and resources, education, limitations, and future directions.

Natural mucosal barriers and COVID-19 in children.

BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODSClinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTSSARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1ß protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSIONThese findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDINGNIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean's COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.

Natural Mucosal Barriers and COVID-19 in Children.

COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with viruses such as influenza where disease manifestations are often more severe in children1. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-alpha2, IFN-gamma, IP-10, IL-8, and IL-1beta were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a more robust innate immune response in children compared to adults contributes to favorable clinical outcomes.

Clinical characteristics of acute lower extremity deep venous thrombosis diagnosed by duplex in patients hospitalized for coronavirus disease 2019.

OBJECTIVE: Little is known about coronavirus disease 2019 (COVID-19)-associated hypercoagulability. We sought to characterize patients with deep venous thrombosis (DVT) identified after admission for COVID-19. METHODS: All adult patients admitted to Montefiore Medical Center from March 1, 2020, to April 10, 2020, and undergoing lower extremity venous duplex for DVT evaluation were included. Patients admitted with suspicion of COVID-19 were divided into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and SARS-CoV-2 negative groups based on in-hospital test results. Patients without clinical suspicion for COVID-19 were not tested. A retrospective case-control study design was used to identify potential risk factors for DVT in patients with COVID-19. Demographic, radiographic, and laboratory values were abstracted and analyzed. RESULTS: During the study period, 3404 patients with confirmed COVID-19 were admitted to the hospital. Of the 135 SARS-CoV-2 patients who underwent duplex scanning, there were 18 (13.3%) noted to have DVT compared with 72 of the 711 patients (10.1%) who were either SARS-CoV-2 negative or untested. The odds ratio for DVT in COVID-19 was 1.35 (95% confidence interval, 0.78-2.34; P = .289). Baseline characteristics for COVID-19 patients with and without DVT were overall similar. COVID-19 patients with DVT had an elevated median first d-dimer (18.88 µg/mL [interquartile range (IQR), 7.79-20.00] vs 2.55 µg/mL [IQR, 1.45-6.28]; P = .002; reference value, <0.5 µg/mL), average in-hospital d-dimer (median, 11.93 µg/mL [IQR, 8.25-16.97] vs 3.54 µg/mL [IQR, 2.05-8.53]; P < .001) and median fibrinogen level (501.0 [IQR, 440.0-629.0] vs 654.5 [IQR, 535.8-780.0]; P = .002; reference range, 187-502 mg/dL). There was a trend to significance for COVID-19 patients with DVT compared with without DVT in median d-dimer levels at the time of the duplex (13.61 µg/mL [IQR, 4.04-19.97] vs 3.58 µg/mL [IQR, 2.51-9.62]; P = .055) and median ferritin levels (1679.0 ng/mL [IQR, 1168.0-2577.0] vs 1103.0 ng/mL [IQR, 703.5-2076.5]; P = .055; reference range, 25-270 ng/mL). Twelve of the 18 patients with COVID who developed DVT did so despite chemical thromboprophylaxis, and 2 developed DVT despite therapeutic anticoagulation CONCLUSIONS: We found only a modestly increased risk of DVT in patients with COVID-19, likely underestimated owing to limitations in duplex testing early in the epidemic. Elevated d-dimer and a less elevated fibrinogen are associated with DVT in patients with COVID-19 who seem to form thrombus despite conventional chemical thromboprophylaxis. Additionally, an increasing d-dimer over time may be a reflection of the development of DVT in patients with COVID-19.

Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients.

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor-α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.

HVEM signaling promotes protective antibody-dependent cellular cytotoxicity (ADCC) vaccine responses to herpes simplex viruses.

Herpes simplex virus (HSV) glycoprotein D (gD) not only is required for virus entry and cell-to-cell spread but also binds the host immunomodulatory molecule, HVEM, blocking interactions with its ligands. Natural infection primarily elicits neutralizing antibodies targeting gD, but subunit protein vaccines designed to induce this response have failed clinically. In contrast, preclinical studies demonstrate that an HSV-2 single-cycle strain deleted in gD, ΔgD-2, induces primarily non-neutralizing antibodies that activate Fcγ receptors (FcγRs) to mediate antibody-dependent cellular cytotoxicity (ADCC). These studies were designed to test the hypothesis that gD interferes with ADCC through engagement of HVEM. Immunization of Hvem-/- mice with ΔgD-2 resulted in significant reduction in HSV-specific IgG2 antibodies, the subclass associated with FcγR activation and ADCC, compared with wild-type controls. This translated into a parallel reduction in active and passive vaccine protection. A similar decrease in ADCC titers was observed in Hvem-/- mice vaccinated with an alternative HSV vaccine candidate (dl5-29) or an unrelated vesicular stomatitis virus-vectored vaccine. Unexpectedly, not only did passive transfer of immune serum from ΔgD-2-vaccinated Hvem-/- mice fail to protect wild-type mice but transfer of immune serum from ΔgD-2-vaccinated wild-type mice failed to protect Hvem-/- mice. Immune cells isolated from Hvem-/- mice were impaired in FcγR activation, and, conversely, addition of gD protein or anti-HVEM antibodies to in vitro murine or human FcγR activation assays inhibited the response. These findings uncover a previously unrecognized role for HVEM signaling in generating and mediating ADCC and an additional HSV immune evasion strategy.

Hospitalist Perspectives of Available Tests to Monitor Volume Status in Patients With Heart Failure: A Qualitative Study.

Acute decompensated heart failure is the leading admitting diagnosis in patients 65 years and older with more than 1 million hospitalizations per year in the US alone. Traditional tools to evaluate for and monitor volume status in patients with heart failure, including symptoms and physical exam findings, are known to have limited accuracy. In contrast, point of care lung ultrasound is a practical and evidenced-based tool for monitoring of volume status in patients with heart failure. However, few inpatient clinicians currently use this tool to monitor diuresis. We performed semi-structured interviews of 23 hospitalists practicing in five geographically diverse academic institutions in the US to better understand how hospitalists currently assess and monitor volume status in patients hospitalized with heart failure. We also explored their perceptions and attitudes toward adoption of lung ultrasound. Hospitalist participants reported poor reliability and confidence in the accuracy of traditional tools to monitor diuresis and expressed interest in learning or were already using lung ultrasound for this purpose. The time required for training and access to equipment that does not impede workflow were considered important barriers to its adoption by interviewees.