Investigation of liquid biopsy analytes in peripheral blood of individuals after SARS-CoV-2 infection.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is linked to severe organ damage. The identification and stratification of at-risk SARS-CoV-2 infected individuals is vital to providing appropriate care. This exploratory study looks for a potential liquid biopsy signal for PACS using both manual and machine learning approaches. METHODS: Using a high definition single cell assay (HDSCA) workflow for liquid biopsy, we analysed 100 Post-COVID patients and 19 pre-pandemic normal donor (ND) controls. Within our patient cohort, 73 had received at least 1 dose of vaccination prior to SARS-CoV-2 infection. We stratified the COVID patients into 25 asymptomatic, 22 symptomatic COVID-19 but not suspected for PACS and 53 PACS suspected. All COVID-19 patients investigated in this study were diagnosed between April 2020 and January 2022 with a median 243 days (range 16-669) from diagnosis to their blood draw. We did a histopathological examination of rare events in the peripheral blood and used a machine learning model to evaluate predictors of PACS. FINDINGS: The manual classification found rare cellular and acellular events consistent with features of endothelial cells and platelet structures in the PACS-suspected cohort. The three categories encompassing the hypothesised events were observed at a significantly higher incidence in the PACS-suspected cohort compared to the ND (p-value < 0.05). The machine learning classifier performed well when separating the NDs from Post-COVID with an accuracy of 90.1%, but poorly when separating the patients suspected and not suspected of PACS with an accuracy of 58.7%. INTERPRETATION: Both the manual and the machine learning model found differences in the Post-COVID cohort and the NDs, suggesting the existence of a liquid biopsy signal after active SARS-CoV-2 infection. More research is needed to stratify PACS and its subsyndromes. FUNDING: This work was funded in whole or in part by Fulgent Genetics, Kathy and Richard Leventhal and Vassiliadis Research Fund. This work was also supported by the National Cancer InstituteU54CA260591.

Experiences and Perspectives on Stressors and Organizational Strategies to Bolster Resiliency During the COVID-19 Pandemic: A Qualitative Study of Health Care Workers at a Tertiary Medical Center.

OBJECTIVE: This qualitative study included a sample of health care workers (HCWs) at a tertiary care center providing direct care to patients with COVID-19 to explore experiences and perceptions regarding care delivery during the COVID-19 pandemic as well as factors that helped HCWs cope with the challenges of the pandemic. Methods: Grounded theory methodology was used to conduct virtual focus groups with a semistructured interview guide May to June 2020. Results: We identified major themes related to (1) HCWs' emotions during the pandemic, (2) the perceived triggers of these feelings, (3) organizational factors that made HCWs feel more supported and appreciated, and (4) personal factors that helped HCWs cope with the pandemic. Conclusion: Results highlighted the stress and challenges associated with exposure to SARS-CoV-2. The findings can help inform interventions to support HCWs during pandemics and other crises.

Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. RESULTS: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Cancer Screening Practices Among Healthcare Workers During the COVID-19 Pandemic.

The COVID-19 pandemic has the potential to impact long-standing efforts to increase adherence to cancer screening guidelines. Healthcare workers (HCWs) experienced significant hardship, but generally have greater access to preventive services, making them a particularly relevant population in which to understand cancer screening behaviors during the pandemic. We report data from 794 HCWs enrolled in the NCI-funded Serological Sciences Network for Coronavirus Associations and Longitudinal Evaluation Study from December 2020 to April 2021. Participants reported lifestyle and screening behaviors during relevant look-back periods which included the pandemic timeframe. Among women between the ages of 40 and 74, 25.7% were overdue for mammographic breast cancer screening. Among participants 50-75 years old, 38.9% were overdue for colorectal cancer screening. The proportion over-due varied according to race/ethnicity. Lifetime low-dose computed tomography lung cancer screening among HCWs age 50-80 years who were smokers was 10.9%. Strategies to address screening disruptions are needed to minimize the impact of later stage of diagnosis.

Rapidly Growing Mycobacterium tuberculosis in the Form of Empyema Necessitans: A Case Report.

We present a case of rapidly growing disseminated Mycobacterium tuberculosis (MTB) that presented as an empyema necessitans (EN) in a 65-year-old woman with a single right lung transplant admitted for progressive dyspnea. While hospitalized, she had daily fevers and was found to have a right-sided chest wall abscess and pleural effusion. Acid-fast bacilli cultures from the abscess and pleural fluid grew MTB within 4 and 6 days, respectively. Blood cultures later grew MTB as well. Upon initiation of rifampin, isoniazid, pyrazinamide, and ethambutol, she developed hemorrhagic pancreatitis and distributive shock secondary to antituberculosis medications and disseminated MTB. Noteworthy features of this case include the rapid rate of MTB culture growth in less than a week, the development of a likely donor-derived MTB EN, and the clinical challenges of MTB screening and MTB infection management in a solid organ transplant recipient.

Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19: A Randomized, Controlled Pilot Trial.

BACKGROUND: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. RESEARCH QUESTION: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? STUDY DESIGN AND METHODS: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. RESULTS: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. INTERPRETATION: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov.

High thrombus burden despite thrombolytic therapy in ST-elevation myocardial infarction in a patient with COVID-19.

Consideration of thrombolysis as first-line reperfusion therapy in patients with COVID-19 and STEMI is recommended by ACC/SCAI guidelines. We describe a patient with COVID-19, who presented with ST-elevation myocardial infarction and was treated with thrombolysis and anticoagulation. He was later found to have a significant persistent thrombus burden requiring thrombectomy and stent placement. Invasive hemodynamics on multiple high-dose pressers revealed a high cardiac output state with low systemic vascular resistance, consistent with distributive rather than cardiogenic shock. Our case illustrates that thrombolytic therapy alone may not be adequate in patients with STEMI and COVID-19, as well as the importance of early invasive hemodynamics in management of shock in patient with STEMI and COVID-19 infection.

A Case Series of Vaping-Associated Lung Injury Requiring Mechanical Ventilation.

OBJECTIVES: Vaping-associated lung injury has rapidly become a nationwide epidemic and a threat to public health. In this case series, we describe unique clinical features of severe vaping-associated lung injury, defined as respiratory failure due to vaping that requires mechanical ventilation. DATA SOURCES: Clinical observation of four patients. STUDY SELECTION: Case series. DATA EXTRACTION: Data and images were extract from medical records after approval was obtained from the institutional review board. DATA SYNTHESIS: Four patients were admitted to the ICU with severe manifestation of vaping-associated lung injury. Although every case required mechanical ventilatory support (venovenous extracorporeal membrane oxygenation in one patient), all patients survived and were discharged without supplemental oxygen. Systemic corticosteroids were administered in three patients and N-acetyl cysteine in one. A postdischarge pulmonary function test in one patient was normal except for mildly decreased diffusing capacity. CONCLUSIONS: Based on our experience, prognosis of severe vaping-associated lung injury appears favorable with aggressive supportive care, although there is evidence from existing literature that mortality rate might rise with increasing disease severity. Underlying mechanism of lung injury might be similar between vaping-associated lung injury and amiodarone pneumonitis. Foamy or lipid-laden macrophages, seen in both conditions, might be a marker of cytotoxicity from substances contained in e-cigarettes, such as vitamin E acetate. Systemic corticosteroids, and possibly N-acetyl cysteine, could be considered as therapeutic adjuncts in vaping-associated lung injury. Serial pulmonary function tests should be obtained in these patients to monitor for potential long-term complications. The primary limitations of this case series are its small sample and lack of longitudinal follow-up data.

Green synthesis of silver nanoparticles using Rubia tinctorum extract and evaluation the anti-cancer properties in vitro.

Cancer is one of the leading causes of human death. Nanotechnology could offer new and optimised anticancer agents in order to fight cancer. It was shown that metal nanoparticles, in particular silver nanoparticles (AgNPs) were effective in cancer therapy. In this study, AgNPs were synthesised using Rubia tinctorum L. extract (Ru-AgNPs). Then, cytotoxicity effects of the Ru-AgNPs against MDA-MB-231 carcinoma cell line and human dermal fibroblast as normal cell line were performed. Furthermore, anti-apoptotic effects of Ru-AgNPs on these cancer and normal cell lines were compared using acridine orange/propidium iodide staining, flow cytometry analysis and real-time qPCR in apoptosis gene markers. Results of UV-vis spectroscopy showed that Ru-AgNPs have a peak at 430 nm, which indicated synthesis of AgNPs. Ru-AgNPs had spherical shape and average size of 12 nm. Ru-AgNPs have cytotoxicity on MDA-MB-231 cells and decrease cancerous cell viability (IC50 = 4 µg/ml/48 h). Ru-AgNPs could induce apoptosis in MDA-MB-231 cells through upregulation of Bax and downregulation of Bcl-2 gene expression. The results opened up new avenues to develop Rubia based metal complexes as an anticancer agent.

Esophageal motor dysfunction and gastroesophageal reflux are prevalent in lung transplant candidates.

BACKGROUND: Gastroesophageal reflux and aspiration contribute to the development of bronchiolitis obliterans and accelerate graft deterioration after lung transplantation (LTx). We evaluated LTx candidates for esophageal motor abnormalities and gastroesophageal reflux. METHODS: Consecutive patients evaluated for LTx underwent 24-hour pH monitoring using a dual-channel pH probe and high-resolution esophageal manometry. High-resolution manometry was also performed in healthy control subjects. The prevalence of abnormal acid exposure was noted in the LTx candidates. RESULTS: Thirty LTx candidates and 10 control subjects were evaluated. Lung transplantation candidates had higher residual upper and lower esophageal sphincter pressures. The mean proportion of peristaltic swallows was 21% lower in LTx candidates. Both hypotensive and aperistaltic swallows were sixfold more prevalent in LTx candidates than in control subjects. All control subjects had normal high-resolution manometry whereas 23 LTx candidates (76.7%) had esophageal peristaltic dysfunction. Abnormal acid exposure time was seen in the proximal and distal esophagus in 25% and 36% of LTx candidates, respectively. Lung transplantation candidates with idiopathic pulmonary fibrosis had more aperistaltic contractions, more negative minimum intrathoracic pressure, and a higher frequency of abnormal distal esophagus acid exposure. The majority of patients with complications after LTx demonstrated motor, anatomic, or pH abnormalities. CONCLUSIONS: Disordered esophageal motor function and gastroesophageal reflux are common in LTx candidates. We believe high-resolution esophageal manometry is a valid tool to use and the abnormalities we identified may be representative of this unique patient population. The role of this study in predicting a worse outcome should be further studied in patients after LTx.