Aerosols modification with H2O2 reduces airborne contamination by dental handpieces.

Objective: We designed an in vitro study to evaluate the efficiency of an 0.5 vol% hydrogen peroxide-based spray in reducing Coronavirus 229E spread during a conventional dental procedure. Methods: A class III cabinet-like chamber was custom-built, using phantoms for both patient and operator. A suspension of HCoV-229E in artificial saliva having a similar viral load to SARS-CoV-2 asymptomatic patients was inoculated inside the patient's phantom mouth. A 10 s-lasting dental procedure was performed using an aerosol-generating air-turbine, with or without high-volume evacuation (HVE). The effect of 0.5 vol% H2O2 cooling spray in reducing viral loads was tested. Viral presence on the operator phantom was assessed by Real-Time quantitative PCR on the mask's outer surface, on the phantom's forehead, and inside its mouth. Results: When the H2O2 cooling spray was used, as compared to the conventional spray, viral loads were significantly lower on all tested sites, falling below the detection limit. Viral loads did not significantly change in any tested site when HVE was used. Conclusion: The use of 0.5 vol% H2O2 cooling spray by dental handpieces drastically reduced the possibility of coronaviruses spread during aerosol-generating dental procedures. This strategy deserves further consideration among the preventive measures to be adopted during the SARS-CoV-2 pandemic.

Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19.

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.

The kidnapping of mitochondrial function associated with the SARS-CoV-2 infection.

Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) leads to multi-organ failure associated with a cytokine storm and septic shock. The virus evades the mitochondrial production of interferons through its N protein and, from that moment on, it hijacks the functions of these organelles. The aim of this study was to show how the virus kidnaps the mitochondrial machinery for its benefit and survival, leading to alterations of serum parameters and to nitrosative stress (NSS). In a prospective cohort of 15 postmortem patients who died from COVID-19, six markers of mitochondrial function (COX II, COX IV, MnSOD, nitrotyrosine, Bcl-2 and caspase-9) were analyzed by the immune colloidal gold technique in samples from the lung, heart, and liver. Biometric laboratory results from these patients showed alterations in hemoglobin, platelets, creatinine, urea nitrogen, glucose, C-reactive protein, albumin, D-dimer, ferritin, fibrinogen, Ca²âº, K⁺, lactate and troponin. These changes were associated with alterations in the mitochondrial structure and function. The multi-organ dysfunction present in COVID-19 patients may be caused, in part, by damage to the mitochondria that results in an inflammatory state that contributes to NSS, which activates the sepsis cascade and results in increased mortality in COVID-19 patients.

Clinical validation of a novel bioluminescence imaging technology for aiding the assessment of carious lesion activity status.

OBJECTIVES: Clinical validation of a bioluminescence imaging system (Cis) as measured by the level of agreement between clinician visual and tactile assessment of carious lesion presence and activity and the presence/absence of elevated luminescence on a tooth surface determined from intraoral image mapping. MATERIALS AND METHODS: This was a regulatory clinical study designed in consultation with the FDA. The design was a prospective, five-investigator, nonrandomized, post-approval, clinical study utilizing the Cis to provide images of elevated calcium ion concentration (indicative of active demineralization) on tooth surfaces via use of a photoprotein. Imaged teeth were identified as "sound" or having "active lesions." Images were scored independently for luminescence. RESULTS: A total of 110 participants aged 7-74 years were imaged. Of the 90 teeth assessed as "sound," 88 were deemed to show no luminescence by the reviewing investigator, a negative percentage agreement of 97.8% (significantly >50% agreement [p < .0001]; one-sided 97.5% confidence interval [CI]: 0.9220). Of the 86 teeth initially assessed as having an "active lesion," 78 were deemed to show luminescence by the reviewing investigator, a positive percentage agreement of 90.7% (significantly >50% agreement [p < .0001]; 97.5% CI: 0.8249). There were no patient-related adverse events. CONCLUSIONS: Results show, with a high level of agreement, that Cis can differentiate tooth surfaces clinically identified as involving active enamel lesions (ICDAS code 2/3), from sound sites (biochemically equivalent to inactive lesions) and that the system is safe for clinical use.

Ocular COVID-19: Eyes as a Reservoir to Conceal and Spread SARSCoV- 2.

Ocular tissues can serve as a reservoir for the SARS-CoV-2 virus which can not only cause conjunctivitis but also serve as a source of infection transmission to others. Additionally, the eye and its tear drainage apparatus can track the SARS-CoV-2 from the eye into the respiratory tract of the patient. The potential ocular presence of the SARS-CoV-2 in the eye of a patient can target ACE2 receptors in the endothelium of the conjunctival vessels and use the lacrimal sac a potential space to evade immune detection and clinical isolation. The recently reported case of COVID-19 after the acquisition of SARS-CoV-2 from a COVID-19 patient should alert the healthcare professionals dealing with COVID-19 patients that wearing masks alone cannot guarantee protection against infection transmission. Further studies, like isolation of SARS-CoV-2 from the eyes of patients with COVID-19, are needed to identify the eyes as a potential source of SARS-CoV-2 infection transmission.

Persistence of Elevated Procalcitonin in a Patient with Coronavirus Disease 2019 Uncovered a Diagnosis of Medullary Thyroid Carcinoma.

OBJECTIVE: During the ongoing coronavirus disease 2019 pandemic, procalcitonin (PCT) levels have proven useful in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at the resolution thereof, inappropriately and persistently high PCT levels may suggest and reveal the presence of other pathologies. We report a patient with severe acute respiratory syndrome coronavirus 2 pneumonia with initially elevated PCT levels that persisted during recovery, prompting the diagnosis of medullary thyroid carcinoma (MTC). METHODS: A 43-year-old man presented with a 2-day history of fever, sneezing, sore throat, and dry cough. His PCT was 94 ng/mL (normal value, 0.00-0.10 ng/mL), and he was positive for severe acute respiratory syndrome coronavirus 2 RNA. RESULTS: Empirical antibiotic therapy was administered for 7 days, but despite a clinical improvement, serum PCT remained high (84 ng/mL). Serum calcitonin (CTN) was 2120 pg/mL (normal, ≤12 pg/mL). Cytologic examination of thyroid nodules and CTN measurement of the aspiration needle washout confirmed MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Lowered CTN (986 pg/mL) and PCT (16 ng/mL) levels were observed 48 hours after surgery. A close follow-up was planned following the results of RET gene analysis. CONCLUSION: PCT can be a useful biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT, even after resolution. In our case, high levels of PCT in a patient with coronavirus disease 2019 pneumonia without signs of bacterial infection led to MTC diagnosis.

Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses.

Coronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible for the global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting the SARS viruses to bypass the host protective response. This work also constitutes a first step in the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus.

Can immunological manipulation defeat SARS-CoV-2? Why G-CSF induced neutrophil expansion is worth a clinical trial: G-CSF treatment against COVID-19.

Immunity against SARS-CoV-2 that is acquired by convalescent COVID-19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue-resident memory T (TRM ) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL-17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site by CCL20 and expand in the presence of IL-23. These nTh17 cells are converted to TRM cells upon encounter with SARS-CoV-2 and continue to exist as ex-Th17 cells, which exert Th1-like immunity during a memory response. G-CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G-CSF may be effective against COVID-19. Administration of G-CSF to patients infected with SARS-CoV-2 is worth a clinical trial.

Autonomic innervation of the carotid body as a determinant of its sensitivity: implications for cardiovascular physiology and pathology.

The motivation for this review comes from the emerging complexity of the autonomic innervation of the carotid body (CB) and its putative role in regulating chemoreceptor sensitivity. With the carotid bodies as a potential therapeutic target for numerous cardiorespiratory and metabolic diseases, an understanding of the neural control of its circulation is most relevant. Since nerve fibres track blood vessels and receive autonomic innervation, we initiate our review by describing the origins of arterial feed to the CB and its unique vascular architecture and blood flow. Arterial feed(s) vary amongst species and, unequivocally, the arterial blood supply is relatively high to this organ. The vasculature appears to form separate circuits inside the CB with one having arterial venous anastomoses. Both sympathetic and parasympathetic nerves are present with postganglionic neurons located within the CB or close to it in the form of paraganglia. Their role in arterial vascular resistance control is described as is how CB blood flow relates to carotid sinus afferent activity. We discuss non-vascular targets of autonomic nerves, their possible role in controlling glomus cell activity, and how certain transmitters may relate to function. We propose that the autonomic nerves sub-serving the CB provide a rapid mechanism to tune the gain of peripheral chemoreflex sensitivity based on alterations in blood flow and oxygen delivery, and might provide future therapeutic targets. However, there remain a number of unknowns regarding these mechanisms that require further research that is discussed.

αvß6-Targeted Molecular PET/CT Imaging of the Lungs After SARS-CoV-2 Infection.

The true impact and long-term damage to organs such as the lungs after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain to be determined. Noninvasive molecularly targeted imaging may play a critical role in aiding visualization and understanding of the systemic damage. We have identified αvß6 as a molecular target; an epithelium-specific cell surface receptor that is low or undetectable in healthy adult epithelium but upregulated in select injured tissues, including fibrotic lung. Herein we report the first human PET/CT images using the integrin αvß6-binding peptide (18F-αvß6-BP) in a patient 2 mo after the acute phase of infection. Minimal uptake of 18F-αvß6-BP was noted in normal lung parenchyma, with uptake being elevated in areas corresponding to opacities on CT. This case suggests that 18F-αvß6-BP PET/CT is a promising noninvasive approach to identify the presence and potentially monitor the persistence and progression of lung damage.

Specialised training in paediatric anaesthesia: Need of the hour.

Paediatric anaesthesia is an upcoming speciality which is gaining wide interest and can be a career choice for the new trainees. The need to develop paediatric anaesthesia as a speciality was realised with the progress in the field of paediatric surgery. The profile of the 'patient' encountered by a paediatric anaesthesiologist spans from an extremely premature neonate on the fringes of survival, to a full-grown adolescent equivalent to an adult. Perioperative morbidity and mortality are 2-3 times higher in infants and neonates compared to adults particularly in middle and low-income countries. The anatomical, physiological, pharmacological variations and presence of congenital cardiac, pulmonary and metabolic diseases in young children make perioperative management challenging. Special expertise and training are required for anaesthetic management of these preverbal children. In India, 3-years DM and 1-year Fellowship courses in paediatric anaesthesia are now available for specialisation. An ideal paediatric anaesthesia training centre should have substantial paediatric and neonatal patient load with exclusive intensive care facility. Paediatric anaesthesiologists, having knowledge of several facets of paediatrics and anaesthesia are capable of coordinating with health care professionals performing procedures outside the operating room. Paediatric anaesthesia, as a career thus offers a great opportunity to enhance quality and safety of anaesthesia in this high-risk surgical population. Persistent coordinated team efforts improve patient outcomes, reduce stress at work and increase job satisfaction.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

The impact of far-UVC radiation (200-230 nm) on pathogens, cells, skin, and eyes - a collection and analysis of a hundred years of data.

Background: The ongoing coronavirus pandemic requires new disinfection approaches, especially for airborne viruses. The 254 nm emission of low-pressure vacuum lamps is known for its antimicrobial effect, but unfortunately, this radiation is also harmful to human cells. Some researchers published reports that short-wavelength ultraviolet light in the spectral region of 200-230 nm (far-UVC) should inactivate pathogens without harming human cells, which might be very helpful in many applications. Methods: A literature search on the impact of far-UVC radiation on pathogens, cells, skin and eyes was performed and median log-reduction doses for different pathogens and wavelengths were calculated. Observed damage to cells, skin and eyes was collected and presented in standardized form. Results: More than 100 papers on far-UVC disinfection, published within the last 100 years, were found. Far-UVC radiation, especially the 222 nm emission of KrCl excimer lamps, exhibits strong antimicrobial properties. The average necessary log-reduction doses are 1.3 times higher than with 254 nm irradiation. A dose of 100 mJ/cm2 reduces all pathogens by several orders of magnitude without harming human cells, if optical filters block emissions above 230 nm. Conclusion: The approach is very promising, especially for temporary applications, but the data is still sparse. Investigations with high far-UVC doses over a longer period of time have not yet been carried out, and there is no positive study on the impact of this radiation on human eyes. Additionally, far-UVC sources are unavailable in larger quantities. Therefore, this is not a short-term solution for the current pandemic, but may be suitable for future technological approaches for decontamination in rooms in the presence of people or for antisepsis.

Spontaneous pneumomediastinum in COVID-19 patients. Case series.

Spontaneous pneumomediastinum is defined as the presence of free air within the mediastinum without an apparent cause such as chest trauma. It is a benign, self-limiting condition that is conservatively treated. Clinical diagnosis is based on two symptoms: chest pain and dyspnea; and on a particular sign: subcutaneous emphysema. It has been reported in patients with influenza A (H1N1) and severe acute respiratory syndrome; however, it has been rarely observed in COVID-19 patients. In this work, we describe six male patients with COVID-19, aged between 27 and 82 years, who presented with spontaneous pneumomediastinum and subcutaneous emphysema; both conditions were completely resorbed with conservative management.

El neumomediastino espontáneo es la presencia de aire libre en el mediastino sin el antecedente de alguna causa como trauma de tórax. Es una condición benigna autolimitada que se trata en forma conservadora. El diagnóstico clínico se basa en dos síntomas: dolor torácico y disnea; y en un signo en particular: enfisema subcutáneo. Ha sido reportado en pacientes con influenza A (H1N1) y síndrome respiratorio agudo grave; sin embargo, ha sido raramente observado en pacientes con COVID-19. En este trabajo describimos seis pacientes del sexo masculino con COVID-19, con edades entre 27 y 82 años, que presentaron neumomediastino espontáneo y enfisema subcutáneo; ambos se reabsorbieron totalmente con manejo conservador.

SARS-CoV-2 detection and sequencing in heart tissue associated with myocarditis and persistent arrhythmia: A case report.

BACKGROUND: SARS-CoV-2 uses the human cell receptor angiotensin-converting enzyme (ACE2). ACE2 is widely present in the cardiovascular system including the myocardium and the conduction system. COVID-19 patients that present severe symptoms have been reported to have complications involving myocardial injuries caused by the virus. Here we report the detection of SARS-CoV-2 by whole genome sequencing in the endocardium of a patient with severe bradycardia. CASE PRESENTATION: We report a case of a 34-year-old male patient with COVID-19 tested by PCR, he started with gastrointestinal symptoms, however, he quickly deteriorated his hemodynamic state by means of myocarditis and bradycardia. After performing an endocardium biopsy, it was possible to identify the presence of SARS-CoV-2 in the heart tissue and to sequence its whole genome using the ARTIC-Network protocol and a modified tissue RNA extraction method. The patient's outcome was improved after a permanent pacemaker was implanted. CONCLUSIONS: It was possible to identify a SARS-CoV-2 clade 20A in the endocardium of the reported patient.

Anticoagulation in the obese patient with COVID-19-associated venous thromboembolism.

A 61-year-old obese man who had recently tested positive for COVID-19 presented to the emergency department following an unwitnessed collapse, with a brief period of unresponsiveness. CT pulmonary angiography confirmed the presence of extensive bilateral pulmonary embolism despite the patient reporting full compliance with long-term dabigatran. The patient was initially anticoagulated with low-molecular-weight heparin and was treated with non-invasive ventilation and dexamethasone for COVID-19 pneumonia. He made a full recovery and was discharged on oral rivaroxaban. His case highlighted some of the common problems encountered when selecting an anticoagulation strategy for obese patients, as well as the lack of definitive evidence to guide treatment decisions. These challenges were further complicated by our incomplete understanding of the underlying mechanisms of COVID-19 coagulopathy, with limited data available regarding the optimal management of thromboembolic complications.

Pulmonary embolism severity before and during the COVID-19 pandemic.

OBJECTIVES: Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019. METHODS: In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records. RESULTS: In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008). CONCLUSION: During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19. ADVANCES IN KNOWLEDGE: During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone.

Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19.

OBJECTIVE: To explore the spectrum of skeletal muscle and nerve pathology of patients who died after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to assess for direct viral invasion of these tissues. METHODS: Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died after SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review. RESULTS: In SARS-CoV-2-positive patients, mean age at death was 67.8 years (range 43-96 years), and the duration of symptom onset to death ranged from 1 to 49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74% (mean 959 U/L, range 29-8,413 U/L). Muscle showed type 2 atrophy in 32 patients, necrotizing myopathy in 9, and myositis in 7. Neuritis was seen in 9. Major histocompatibility complex-1 (MHC-1) expression was observed in all cases of necrotizing myopathy and myositis and in 8 additional patients. Abnormal expression of myxovirus resistance protein A (MxA) was present on capillaries in muscle in 9 patients and in nerve in 7 patients. SARS-CoV-2 immunohistochemistry was negative in muscle and nerve in all patients. In the 10 controls, muscle showed type 2 atrophy in all patients, necrotic muscle fibers in 1, MHC-1 expression in nonnecrotic/nonregenerating fibers in 3, MxA expression on capillaries in 2, and inflammatory cells in none, and nerves showed no inflammatory cells or MxA expression. CONCLUSIONS: Muscle and nerve tissue demonstrated inflammatory/immune-mediated damage likely related to release of cytokines. There was no evidence of direct SARS-CoV-2 invasion of these tissues. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that muscle and nerve biopsies document a variety of pathologic changes in patients dying of coronavirus disease 2019 (COVID-19).

A Case of Failure of EkoSonic™ Endovascular System in the Treatment of Submassive Pulmonary Embolism.

Submassive pulmonary embolism (SPE) is characterized by the presence of right ventricular (RV) strain as visualized on echocardiogram or CT scan with brain natriuretic peptide (BNP) and/or troponin elevation. The condition accounts for 20-25% of all pulmonary embolism (PE) cases. In cases of SPE, catheter-directed thrombolysis (CDT) is generally considered in the presence of severe hypoxemia, worsening RV dysfunction, patients with increasing tachycardia and elevated troponins, free-floating thrombus in the right atrium or RV, and presence of extensive clot burden. EkoSonic™ Endovascular System (EKOS; Boston Scientific, Marlborough, MA) has been successfully used to treat cases of PE even where systemic thrombolytic therapy has failed. However, in this article, we describe a unique case of the failure of EKOS in treating a 71-year-old African American man who presented to the hospital with progressively worsening chest pain, shortness of breath, and fatigue. He was suspected to have SPE; however, a CT pulmonary angiogram could not be performed to estimate the clot burden due to an acute kidney injury. He was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia during the hospitalization and had a delayed EKOS procedure with minimal improvement in oxygenation and clot burden. He subsequently underwent half-dose systemic thrombolytic therapy with complete resolution of his symptoms. Given our success with half-dose systemic therapy, we propose that it may be considered as a "rescue therapy" in cases where EKOS fails to deliver results.

Mass Spectrometric Analysis of Urine from COVID-19 Patients for Detection of SARS-CoV-2 Viral Antigen and to Study Host Response.

SARS-CoV-2 infection has become a major public health burden and affects many organs including lungs, kidneys, the liver, and the brain. Although the virus is readily detected and diagnosed using nasopharyngeal swabs by reverse transcriptase polymerase chain reaction (RT-PCR), detection of its presence in body fluids is fraught with difficulties. A number of published studies have failed to detect viral RNA by RT-PCR methods in urine. Although microbial identification in clinical microbiology using mass spectrometry is undertaken after culture, here we undertook a mass spectrometry-based approach that employed an enrichment step to capture and detect SARS-CoV-2 nucleocapsid protein directly from urine of COVID-19 patients without any culture. We detected SARS-CoV-2 nucleocapsid protein-derived peptides from 13 out of 39 urine samples. Further, a subset of COVID-19 positive and COVID-19 negative urine samples validated by mass spectrometry were used for the quantitative proteomics analysis. Proteins with increased abundance in urine of SARS-CoV-2 positive individuals were enriched in the acute phase response, regulation of complement system, and immune response. Notably, a number of renal proteins such as podocin (NPHS2), an amino acid transporter (SLC36A2), and sodium/glucose cotransporter 5 (SLC5A10), which are intimately involved in normal kidney function, were decreased in the urine of COVID-19 patients. Overall, the detection of viral antigens in urine using mass spectrometry and alterations of the urinary proteome could provide insights into understanding the pathogenesis of COVID-19.