Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (14)

ORF3a (2)

ComplexRdRp (2)

ProteinN (2)

ProteinE (1)


SARS-CoV-2 Proteins
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    The second wave of COVID-19 MESHD incidence and deaths MESHD in Germany - driven by values, social status and migration background? A county-scale explainable machine learning approach

    Authors: Gabriele Doblhammer; Constantin Reinke; Daniel Kreft

    doi:10.1101/2021.04.14.21255474 Date: 2021-04-14 Source: medRxiv

    There is a general consensus that SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths MESHD have hit lower social groups the hardest, however, for Germany individual level information on socioeco-nomic characteristics of infections and deaths does not exist. The aim of this study was to identify the key features explaining SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths during the upswing of the second wave in Germany. We considered information on COVID-19 MESHD diagnoses and deaths from 1. October to 15. De-cember 2021 on the county-level, differentiating five two-week time periods. We used 155 indicators to characterize counties in nine geographic, social, demographic, and health do-mains. For each period, we calculated directly age-standardized COVID-19 MESHD incidence and death MESHD rates on the county level. We trained gradient boosting models to predict the inci-dence and death rates with the 155 characteristics of the counties for each period. To ex-plore the importance and the direction of the correlation of the regional indicators we used the SHAP HGNC procedure. We categorized the top 20 associations identified by the Shapley values into twelve categories depicting the correlation between the feature and the outcome. We found that counties with low SES were important drivers in the second wave, as were those with high international migration and a high proportion of foreigners and a large nurs-ing home population. During the period of intense exponential increase in infections, the proportion of the population that voted for the Alternative for Germany (AfD) party in the last federal election was among the top characteristics correlated with high incidence and death MESHD rates. We concluded that risky working conditions with reduced opportunities for social distancing and a high chronic disease burden put populations in low-SES counties at higher risk of SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths. In addition, noncompliance with Corona measures and spill-over effects from neighbouring counties increased the spread of the virus. To fur-ther substantiate this finding, we urgently need more data at the individual level.

    Case fatality rates for COVID-19 MESHD are higher than case fatality rates for motor vehicle accidents for individuals over 40 years of age

    Authors: Arjun Puranik; Michiel J.M. Niesen; Emily Lindemer; Patrick Lenehan; Tudor Cristea-Platon; Colin Pawlowski; Venky Soundararajan

    doi:10.1101/2021.04.09.21255193 Date: 2021-04-13 Source: medRxiv

    The death toll of the COVID-19 pandemic MESHD has been unprecedented, due to both the high number of SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD and the seriousness of the disease resulting from these infections. Here, we present mortality rates and case fatality rates for COVID-19 MESHD over the past year compared with other historic leading causes of death MESHD in the United States. Among the risk categories considered, COVID-19 MESHD is the third leading cause of death MESHD for individuals 40 years old and over, with an overall annual mortality rate of 325 deaths MESHD per 100K individuals, behind only cancer MESHD (385 deaths per 100K individuals) and heart disease MESHD (412 deaths per 100K individuals). In addition, for individuals 40 years old and over, the case fatality rate for COVID-19 MESHD is greater than the case fatality rate for motor vehicle accidents. In particular, for the age group 40-49, the relative case fatality rate of COVID-19 MESHD is 1.5 fold (95% CI: [1.3, 1.7]) that of a motor vehicle accident, demonstrating that SARS-CoV-2 infection MESHD may be significantly more dangerous than a car crash for this age group. For older adults, COVID-19 MESHD is even more dangerous, and the relative case fatality rate of COVID-19 MESHD is 29.4 fold (95% CI: [23.2, 35.7]) that of a motor vehicle accident for individuals over 80 years old. On the other hand, motor vehicle accidents have a 4.5 fold (95% CI: [3.9, 5.1]) greater relative case fatality rate compared to COVID-19 MESHD for the age group of 20-29 years. These results highlight the severity of the COVID-19 pandemic MESHD especially for adults above 40 years of age and underscore the need for large-scale preventative measures to mitigate risks for these populations. Given that FDA-authorized COVID-19 MESHD vaccines have now been validated by multiple studies for their outstanding real-world effectiveness and safety, vaccination of all individuals who are over 40 years of age is one of the most pressing public health priorities of our time.

    Effect of Tocilizumab on ventilator free days composite outcome in SARS-CoV-2 patients. A retrospective competing risk analysis.

    Authors: Ahmed F. Mady; Basheer Abdulrahman; Omar E. Ramadan; Shahzad A. Mumtaz; Mohammed A. Al-Odat; Ahmed Kuhail; Rehab Altoraifi; Rayan Alshae; Abdulrahman M. Alharthy; Dimitrios Karakitsos; Waleed Th. Aletreby

    doi:10.1101/2021.04.01.21254794 Date: 2021-04-07 Source: medRxiv

    Background: SARS CoV 2 infection MESHD demonstrates a wide range of severity, the more severe cases demonstrate a cytokine storm with elevated serum interleukin 6, hence IL 6 receptor HGNC antibody Tocilizumab was tried for the management of severe cases. Objectives: The effect of Tocilizumab treatment on the composite outcome of ventilator free days, among critically ill SARS CoV MESHD 2 patients. Method: Retrospective observational propensity score matching study, comparing mechanically ventilated patients upon ICU admission who received Tocilizumab to a control group. Utilizing competing risk analysis method, and reporting subdistributional hazard ratio of a composite outcome of ventilator free days at day 28. Results: 29 patients in the intervention group were compared to 29 patients in the control group. Matched groups were similar at base line. The primary outcome of ventilator free days was higher in the intervention group (SHR 2.7, 95% CI: 1.2 to 6.3; p = 0.02), crude ICU mortality rate was not different between Tocilizumab and control groups (37.9% versus 62% respectively, p = 0.1), actual ventilator free days were significantly longer in Tocilizumab group (mean difference 4.7 days, 95% CI 1.1 to 8.3; p = 0.02). Sensitivity analysis by Cox regression showed a significantly lower hazard ratio of death MESHD in Tocilizumab group (HR 0.49, 95% CI: 0.25 to 0.97; p = 0.04). While there was no difference in grown positive cultures among groups (55.2% in Tocilizumab group versus 34.5% in the control, 95% CI of difference: -7.11% to 54.4%; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator free days at day 28 among mechanically ventilated SARS-CoV-2 patients, it is associated with significantly longer actual ventilator free days, and insignificantly lower mortality and superinfection.

    Statins Are Associated with Improved 28-day Mortality in Patients Hospitalized with SARS-CoV-2 Infection MESHD

    Authors: Zoe N Memel; Jenny J Lee; Andrea S Foulkes; Raymond T Chung; Tanayott Thaweethai; Patricia P Bloom

    doi:10.1101/2021.03.27.21254373 Date: 2021-04-06 Source: medRxiv

    Background: Statins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD. Objective: We evaluated the effect of statins on mortality in four groups hospitalized with ( SARS-CoV-2) infection MESHD (continued statin, newly initiated statin, discontinued statin, never on statin). Design: In a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection MESHD, the outcome of death MESHD, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups. Setting: Academic medical center in the United States Participants: Patients hospitalized with SARS-CoV-2 infection MESHD Measurements: 28-day mortality, ICU admission, or discharge Results: Among 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger. Limitation: Observational design Conclusion: Statin therapy during hospitalization for SARS-CoV-2 infection MESHD, including new initiation and continuation of therapy, was associated with reduced short-term mortality.

    Evaluation of the ROX HGNC index in SARS-CoV-2 Acute Respiratory failure MESHD treated with both High-Flow Nasal Oxygen (HFNO) and Continuous Positive Airway Pressure ( CPAP HGNC)

    Authors: Hakim Ghani; Michael Shaw; Phyoe Pyae; Rigers Cama; Meghna Prabhakar; Alessio Navarra; Janice Yu Ji Lee; Felix Chua; Rahul Mogal; Andrew Barlow; Nazril Nordin; Rama Vancheeswaran

    doi:10.1101/2021.03.23.21254203 Date: 2021-03-24 Source: medRxiv

    Background: Non-invasive respiratory support including high-flow nasal oxygen (HFNO), and continuous positive airway pressure ( CPAP HGNC) have been used to provide therapy in selected SARS-CoV-2 patients with acute respiratory failure MESHD ( ARF MESHD). The value of the ROX HGNC index, a validated benchmark for outcomes in HFNO is unknown in CPAP HGNC. Objective: Can the ROX HGNC, a validated benchmark in HFNO be used for measuring treatment outcomes of CPAP HGNC in SARS-COV-2 ARF MESHD? Study Design and Methods: A non-randomised prospective protocol driven observational non-intensive care unit study in 130 SARS-COV-2 patients with ARF MESHD treated with non-invasive therapy from March 2020 to January 2021. The primary end point was failure of therapy ( death MESHD or escalation). Secondary outcomes included time to failure including invasive mechanical ventilation (IMV) or death MESHD, the effect of escalation to CPAP HGNC from HFNO and the utility of ROX HGNC in ARF MESHD. Results: HFNO was better than CPAP HGNC in treating SARS-COV-2 ARF MESHD: 17/35 (48.5%) with successful HFNO therapy versus 24/95 (25.2%) with CPAP HGNC. The ROX HGNC index was more sensitive to outcomes with CPAP HGNC compared to HFNO and distinguished treatment failure early at 1, 4, 6, 12, and 24 hours with the highest sensitivity at 24 hours ( ROX HGNC-24h). The AUC for the ROX-24h was 0.77 for HFNO (P<0.0001), and 0.84 for CPAP HGNC (P<0.0001). The ROX HGNC-24h cut-points predicted failure with HFNO when < 3.9 (PPV 71%, NPV 75%) and CPAP HGNC < 4.3 (PPV 75%, NPV 91%). For success, ROX HGNC-24h cut-points of 7.6 for HFNO (PPV 85%, NPV 48%) and 6.1 for CPAP HGNC (PPV 88%, NPV 62%) were observed. Escalation from HFNO to CPAP HGNC was mostly not successful. Conclusion: ARF MESHD in SARS-COV-2 can be successfully managed by non-invasive support. The ROX HGNC index, validated for HFNO, provides a timely, low resource measure for both HFNO and CPAP HGNC avoiding delayed intubation. Trial registration: Study approved by NHS HRAREC (20/ HRA MESHD/2344;ethics 283888)

    Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19 MESHD

    Authors: Paulo Sérgio da Silva Santos; Bernardo da Fonseca Orcina; Rafael Rahal Guaragna Machado; Fabiano Vieira Vilhena; Lucas Marques da Costa Alves; Mariana Schutzer Ragghianti Zangrando; Rodrigo Cardoso de Oliveira; Mariana Quirino Silveira Soares; Andréa Name Colado Simão; Emilene Cristine Izu Nakamura Pietro; Juliana Pescinelli Garcia Kuroda; Ivanilda Aparecida de Almeida Benjamim; Danielle Bastos Araujo; Sérgio Hiroshi Toma; Lourival Flor; Koiti Araki; Edison Luiz Durigon

    doi:10.21203/ Date: 2021-03-14 Source: ResearchSquare

    Background: The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. Methods: The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD MESHD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19 MESHD. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n=20) or nonactive mouthwash (control group NAM HGNC/n=21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death MESHD were also evaluated. Results: The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 MESHD viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity MESHD. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM HGNC group (7 days) (p=0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM HGNC group needed ICU care, and 50% of this ICU subgroup passed way, p=0.0207). Conclusions: This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 MESHD treatment presented no contraindication and reduced the hospital stay period. Trial Registration: The clinical study was registered at REBEC - Brazilian Clinical Trial Register (RBR-58ftdj).

    Plasma ACE2 HGNC levels predict outcome of COVID-19 MESHD in hospitalized patients

    Authors: Tue W Kragstrup; Helene S Singh; Ida Grundberg; Ane L L Nielsen; Felice Rivellese; Arnav Mehta; Marcia B Goldberg; Michael Filbin; Per Qvist; Bo Martin Bibby

    doi:10.1101/2021.03.08.21252819 Date: 2021-03-10 Source: medRxiv

    Background Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) binds to angiotensin converting enzyme 2 ( ACE2 HGNC) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 ( COVID-19 MESHD). COVID-19 MESHD is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome MESHD and death MESHD. Methods This study used data from a large longitudinal study of 306 COVID-19 MESHD positive patients and 78 COVID-19 MESHD negative patients (MGH Emergency Department COVID-19 MESHD Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 MESHD outcomes scale. The samples were run on the Olink Explore 1536 platform which includes measurement of the ACE2 HGNC protein. Findings High baseline levels of ACE2 HGNC in plasma from COVID-19 MESHD patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 HGNC in plasma from COVID-19 MESHD patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 HGNC in plasma from COVID-19 MESHD patients with hypertension MESHD were significantly higher compared to patients without hypertension MESHD (P = 0.0045). The plasma ACE2 HGNC levels were also significantly higher in COVID-19 MESHD patients with pre-existing heart conditions and kidney disease MESHD compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 HGNC levels comparing patients with or without pre-existing lung disease MESHD, diabetes MESHD, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 HGNC and worse WHOmax category during 28 days were more pronounced in COVID-19 MESHD positive patients compared with COVID-19 MESHD negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 HGNC is potentially valuable in predicting COVID-19 MESHD outcomes. Further, ACE2 HGNC levels could be a link between severe COVID-19 MESHD disease and its risk factors, namely hypertension MESHD, pre-existing heart disease MESHD and pre-existing kidney disease MESHD. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 HGNC and ACE1 HGNC activity. This is interesting because ACE1 HGNC (serum ACE HGNC) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19 MESHD.

    Tocilizumab efficacy in COVID-19 MESHD patients is associated with respiratory severity-based stages

    Authors: Melchor Alvarez-Mon; Angel Asunsolo; Jose Sanz; Benjamin Munoz; Jose Alberto Arranz-Caso; Maria Novella Mena; Cristina Hernandez-Gutierrez; Jorge Navarro; Maria Cristina Lozano Duran; Juan Arevalo Serrano; Rocio Heche Sanchez; Lara Bravo Quiroga; Julio Flores Segovia; Marta Garcia Sanchez; Aida Gutierrez Garcia; Ana Perez; Marta Herrero; Nieves Plana; Daniel Troncoso; Gorjana Rackov; Carlos Martinez-A; Dimitrios Balomenos

    doi:10.1101/2021.03.04.21252167 Date: 2021-03-09 Source: medRxiv

    Background: Tocilizumab treatment is investigated, and effectiveness in ICU-admitted COVID-19 MESHD patients has been reported. Although controversy exists regarding the efficacy of tocilizumab treatment, it has been suggested that tocilizumab might show positive results depending on patient severity status. We examined an association between tocilizumab and distinct disease severity stages. Methods and Findings: From March 3 to March 23 2020, 494 consecutively admitted COVID-19 MESHD patients received tocilizumab or standard treatment alone. Data were obtained retrospectively. Clinical respiratory severity ( CRS MESHD) stages were defined by patient oxygenation status and were also associated to scores of WHO clinical progression scale. We categorized patients in three stages, mild/moderate CRS1 HGNC (FiSpO2<0.35; WHO score 5), moderate/severe CRS2 HGNC (FiO2=0.5/high flow mask; WHO score 6) and severe/critical CRS3 (FiO2<80%/high flow/prone position or mechanical ventilation; score>6). The primary outcome was the composite of death MESHD or ICU admission in patients of stages CRS1 HGNC, CRS2 HGNC, and CRS3, as well as in total patients. We also addressed mortality alone in total patients. Kaplan-Maier curves, Cox HGNC proportional regression and inverse probability weighting marginal structural models were used. We conducted the study from March 3 to April 7 2020 with broad-ranged severity patients; 167 tocilizumab-treated and 327 untreated. CRS1 HGNC patients showed no apparent benefit after treatment, while the risk of the primary outcome was greatly reduced in CRS2 HGNC treated participants ((HR=0.22; 95% CI (0.16-0.44)). Moreover, tocilizumab treatment was associated with significantly decreased CRS2 HGNC patient proportion that reached the outcome compared to non-treated controls (27.8.0% vs. 65.4%; p<0.001). Severe/critical CRS3 patients, also showed benefit after treatment (HR=0.38; 95% CI (0.16-90)), although not as robust as was that of CRS2 HGNC treated individuals. Tocilizumab was associated with reduced outcome risk in total patients (HR=0.42; 95% CI (0.26-0.66)) after CRS adjustment, but not if CRS classification was not accounted as confounding factor (HR=1.19; 95% CI (0.84-1.69)). The outcome of mortality alone upon tocilizumab treatment was significant (HR=0.58; 95% CI (0.35-0.96)) after accounting for CRS classification. Conclusions: Tocilizumab treatment is associated with reduced COVID-19 MESHD escalation in CRS2 HGNC patients, suggesting efficacy in moderate/severe non-ICU-admitted patients. CRS classification could represent an essential confounding factor in evaluating tocilizumab in studies of broad-ranged severity patients.

    SARS-CoV-2 infects blood MESHD monocytes to activate NLRP3 HGNC and AIM2 HGNC inflammasomes, pyroptosis and cytokine release

    Authors: Caroline Junqueira; Angela Crespo; Shahin Ranjbar; Jacob Ingber; Blair Parry; Sagi David; Luna B de Lacerda; Mercedes Lewandrowski; Sarah Alden Clark; Felicia Ho; Setu Vora; Valerie Leger; Caroline Beackes; Justin Margolin; Nicole Russell; Lee Gehrke; Upasana Das Adhikari; Lauren Henderson; Erin Janssen; Douglas Kwon; Chris Sander; Jonathan Abraham; Michael Filbin; Marcia B. Goldberg; Hao Wu; Mehta Gautam; Steven Bell; Anne Goldfeld; Judy Lieberman

    doi:10.1101/2021.03.06.21252796 Date: 2021-03-08 Source: medRxiv

    SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure MESHD and death MESHD in some patients. Although severe COVID-19 MESHD disease is linked to exuberant inflammation MESHD, how SARS-CoV-2 triggers inflammation MESHD is not understood. Monocytes are sentinel blood cells that sense invasive infection MESHD to form inflammasomes that activate caspase-1 HGNC and gasdermin D HGNC ( GSDMD HGNC GSDMD MESHD) pores, leading to inflammatory death MESHD (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that ~10% of blood monocytes in COVID-19 MESHD patients are dying and infected with SARS-CoV-2. Monocyte infection, which depends on antiviral antibodies, activates NLRP3 HGNC and AIM2 HGNC inflammasomes, caspase-1 HGNC and GSDMD HGNC cleavage and relocalization. Signs of pyroptosis (IL-1 family cytokines, LDH) in the plasma correlate with development of severe disease. Moreover, expression quantitative trait loci (eQTLs) linked to higher GSDMD HGNC expression increase the risk of severe COVID-19 MESHD disease (odds ratio, 1.3, p<0.005). These findings taken together suggest that antibody-mediated SARS-CoV-2 infection MESHD of monocytes triggers inflammation MESHD that contributes to severe COVID-19 MESHD disease pathogenesis.

    Endotracheal application of ultraviolet A light in critically ill severe acute respiratory syndrome coronavirus-2 MESHD patients: A first-in-human study

    Authors: Ali Rezaie; Gil Y Melmed; Gabriela Leite; Ruchi Mathur; Will Takakura; Isabel Pedraza; Michael Lewis; Rekha Murthy; George Chaux; Mark Pimentel

    doi:10.1101/2021.03.05.21252997 Date: 2021-03-08 Source: medRxiv

    BackgroundPromising preclinical experiments show that, under specific and monitored conditions, ultraviolet-A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. We aimed to evaluate the safety and effects of UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with SARS-CoV-2 infection MESHD. MethodsFive newly intubated mechanically ventilated adults with SARS-CoV-2 infection MESHD, with an endotracheal tube size 7.5mm or greater, were treated with UVA for 20 minutes daily for 5 days, and followed for 30 days. ResultsFive subjects were enrolled (mean age 56.6yrs, 3 male). At baseline, all subjects scored 9/10 on the WHO clinical severity scale (10= death MESHD) with predicted mortality ranging from 21 to 95%. Average log changes in endotracheal viral load from baseline to day 5 and day 6 were -2.41 (range -1.16 to -4.54; Friedman P=0.002) and -3.20 (range -1.20 to -6.77; Friedman P<0.001), respectively. There were no treatment-emergent adverse events. One subject died 17 days after enrollment due to intracranial hemorrhagic MESHD complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, the slope of viral load reduction during UVA treatment correlated with the slope of improvement in clinical WHO severity score over time (Spearman rho=1, P<0.001). ConclusionIn this first-in-human study, endotracheal UVA therapy under specific and monitored settings, was safe with a significant reduction in respiratory SARS-CoV-2 MESHD viral burden over the treatment period. Trial #NCT04572399. Key MessagesO_LIWhat is the key question? Can endotracheal narrow-band UVA therapy be a safe and effective treatment for severe SARS-CoV-2 infection MESHD? C_LIO_LIWhat is the bottom line? Under specific and monitored settings, endotracheal UVA light therapy may be an effective treatment for SARS-CoV-2 infection MESHD. Endotracheal UVA light therapy appears to be well tolerated in critically ill patients with SARS-CoV-2 infection MESHD. C_LIO_LIWhy read on? This is the fist-in-human trial of internal UVA therapy using a alternative novel approach to combat COVID-19 MESHD. C_LI

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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