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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022:3418-3421, 2022.
Article in English | PubMed | ID: covidwho-2018752

ABSTRACT

We suggested a unified system with core components of data augmentation, ImageNet-pretrained ResNet-50, cost-sensitive loss, deep ensemble learning, and uncertainty estimation to quickly and consistently detect COVID-19 using acoustic evidence. To increase the model's capacity to identify a minority class, data augmentation and cost-sensitive loss are incorporated (infected samples). In the COVID-19 detection challenge, ImageNet-pretrained ResNet-50 has been found to be effective. The unified framework also integrates deep ensemble learning and uncertainty estimation to integrate predictions from various base classifiers for generalisation and reliability. We ran a series of tests using the DiCOVA2021 challenge dataset to assess the efficacy of our proposed method, and the results show that our method has an AUC-ROC of 85.43 percent, making it a promising method for COVID-19 detection. The unified framework also demonstrates that audio may be used to quickly diagnose different respiratory disorders.

3.
Conference on Global Medical Engineering Physics Exchanges/Pan American Health Care Exchanges (GMEPE/PAHCE) ; 2022.
Article in English | Web of Science | ID: covidwho-1985448

ABSTRACT

The expanded use of the Masi ventilators to more regions of Peru is important, particularly for regions located at high altitudes, due to the ventilatory support latent need, which also represents a challenge in the calibration and the adjustment of metrological parameters to ensure its correct performance. In a previous study, in Puno city at 3800 m.a.s.l., it was found an error above 15.0% (minimum tolerance) in the tidal volume, for which a negative correction of 25.0% was applied. In the present study, a Masi ventilator was transported to Chachapoyas city, at an altitude of 2400 m.a.s.l. to continue evaluating the effect of altitude on the parameters of the device. Once there, ventilators were acclimated and calibrated. Tidal volume, inspiration-expiration ratio (LE), positive endexpiratory pressure (PEEP), peak inspiratory flow (PIF) and peak inspiratory pressure (PIP) were tested, and the maximum percentages errors presented were 13.5% and 13.9% in the tidal volume and the PIF, respectively. For that reason, although errors were under 15.0%, an update of the software of Masi was needed, applying a negative correction of 14.0%. Then, the parameters were tested again obtaining results with errors below 6.0% and 8.0% in volume controlled an pressure controlled ventilation modes, respectively. These results allowed the use of the Masi ventilator at ICU area. Finally, a software update for the Masi ventilator is performed by applying a linear equation that relates altitudes and percentage errors tested.

4.
Gastroenterology ; 162(7):S-1008, 2022.
Article in English | EMBASE | ID: covidwho-1967396

ABSTRACT

BACKGROUND: Immune-modulating medications for inflammatory bowel diseases (IBD) have been associated with suboptimal vaccine responses. There is conflicting data with SARS-CoV-2 vaccination. METHODS: We measured SARS-CoV-2 vaccine immunogenicity at 2 weeks post 2nd mRNA vaccine in IBD patients as compared to normal healthy donors (NHD). We measured humoral immune responses to SARS-CoV-2: anti-spike Immunoglobulin G (IgG) and anti-receptor binding domain (RBD) IgG were measured by ELISA, and neutralizing antibody titers were measured using recombinant, reporter SARS-CoV-2. Antigen specific memory B cells were measured using recombinant SARS-CoV-2 proteins. Activation induced marker T cell (AIM) assays were performed using SARS-CoV-2 spike megapools. Immunophenotyping was performed by flow cytometry. RESULTS: We enrolled 29 patients with IBD (19 with Crohn's disease, 10 with ulcerative colitis) on infliximab (IFX) monotherapy (N=9), IFX combination therapy with a thiopurine (N=9), vedolizumab monotherapy (N= 11) as compared to matched NHD (N=12). At 2 weeks post vaccination, all subjects made detectable anti-spike IgG and anti-RBD IgG. There were no differences in anti-spike IgG titers among the different groups. IBD patients on IFX monotherapy, but not IBD patients on IFX combination therapy or vedolizumab monotherapy, had lower anti-RBD and neutralization titers as compared to NHD (p-value: 0.041 and 0.023, respectively) (Fig. 1). There were no significant differences in the percentage of spike-specific or RBD-specific memory B cells in IBD patients as compared to NHD (Fig. 1). There were no differences in the percentage of spike-specific CD4+ or CD8+ T cells in all IBD patients as compared to NHDs (Fig. 2). CONCLUSIONS: We demonstrate overall comparable and perserved cell-mediated immunity to SARS-CoV-2 vaccination in a small cohort of IBD patients treated with a range of different immune-modulating medications as compared to healthy controls. Larger numbers of patients are needed to validate these findings.

5.
IEEE Internet of Things Journal ; : 1-1, 2022.
Article in English | Scopus | ID: covidwho-1961407

ABSTRACT

The COVID-19 pandemic has caused a high rate of infection, and thus effective epidemic prevention measures of avoiding the second spread of COVID-19 in hospitals are major challenges for healthcare workers. Hospitals, where medicines are collected, are vulnerable to the rapid spread of COVID-19. Using the remote health monitoring technology of the Internet of Things (IoT) to automatically monitor and record the basic medical information of patients, reduce the workload of healthcare workers, and avoid direct contact with healthcare workers to cause secondary infections is an important research topic. This research proposes a new artificial intelligence solution based on the IoT, replacing existing medicine stations and recognizing medicine bags through the state-of-the-art optical character recognition (OCR) model and PP-OCR v2. The use of optical character recognition in identification of medicine bags can replace healthcare workers in data recording. In addition, this research proposes an administrator management and monitoring system to monitor the equipment and provide a mobile application for patients to check the latest status of medicine bags in real time, and record their medication times. The results of the experiments indicate that the recognition model works very well in different conditions (up to 80.76% in PP-OCR v2 and 94.22% in PGNet), which supports both Chinese and English languages. IEEE

6.
Journal of Food and Drug Analysis ; 30(2):252-270, 2022.
Article in English | Web of Science | ID: covidwho-1918368

ABSTRACT

On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3-4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas;additionally, it increased the expression of several immune markers of lung injury - including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications.

8.
Topics in Antiviral Medicine ; 30(1 SUPPL):54-55, 2022.
Article in English | EMBASE | ID: covidwho-1880082

ABSTRACT

Background: The COVID-19 pandemic led to significant disruptions in the provision of routine medical services. Myriad pandemic-related factors such as access to healthcare facilities, virtual care delivery, social distancing, changes in sexual behaviors, and periodic swab shortages may have affected detection rates for HIV and other sexually transmitted infections (STIs). Thus, we evaluated trends in testing and diagnoses of chlamydia, gonorrhea, syphilis, and HIV from 2017 to 2020 in a large integrated health system in the United States. Methods: We conducted a retrospective study using electronic health records among individuals ages ≥12 years enrolled in the Kaiser Permanente Southern California (KPSC) system. For each year from 2017 to 2020, we assessed the rates per 100,000 person-years of tests conducted and new positive results for genital and extragenital chlamydia, gonorrhea, syphilis, and HIV. Case definitions for chlamydia and gonorrhea included newly positive laboratory results in the absence of any other positive test within the past 30 days, or a positive test after a negative test within a 30-day period. Case definitions for syphilis included any new four-fold increase in RPR titer compared to the immediate prior RPR titer obtained within a 1-year period. We used Poisson regression to estimate rate ratios (RR) for each outcome, comparing pre-pandemic periods (January 2017 to February 2020) to the pandemic period (March to December 2020). Results: The study included a population of more than 4 million KPSC members yearly. During the pre-pandemic period, rates of testing remained stable or modestly increased, whereas case rates increased for syphilis and chlamydia, and decreased for gonorrhea and HIV (Table 1). Compared to the pre-pandemic period, testing rates were significantly lower from March to December 2020 for all STIs and HIV (range of RR 0.69-0.83). HIV/STI diagnosis rates were 7-29% lower during the pandemic for HIV (RR 0.74 [0.66-0.83]), chlamydia (RR 0.71 [95% CI.70-0.73]), and gonorrhea (RR 0.93 [0.89-0.96]), but higher for syphilis (RR 1.32 [1.27, 1.37]). Conclusion: We observed profound reductions in testing and diagnosis rates for chlamydia, gonorrhea, and HIV during the COVID-19 pandemic in Southern California compared to the pre-pandemic period. Despite lower pandemic period testing rates, syphilis diagnoses increased. These findings suggest the pandemic had an adverse impact on identification of STIs, which may impede efforts to curb STIs and the HIV epidemic.

10.
American Family Physician ; 105(2):135-136, 2022.
Article in English | EMBASE | ID: covidwho-1820616
11.
Journal of Allergy and Clinical Immunology ; 149(2):AB212-AB212, 2022.
Article in English | Web of Science | ID: covidwho-1798270
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(3): 399-404, 2022 Mar 20.
Article in Chinese | MEDLINE | ID: covidwho-1791799

ABSTRACT

OBJECTIVE: To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak. METHODS: A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed. RESULTS: A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak. CONCLUSION: TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.


Subject(s)
COVID-19 , Mutation , SARS-CoV-2 , COVID-19/virology , Genome, Viral , Humans , SARS-CoV-2/genetics
13.
Open Forum Infectious Diseases ; 8(SUPPL 1):S16-S17, 2021.
Article in English | EMBASE | ID: covidwho-1746815

ABSTRACT

Background. mRNA vaccines for coronavirus disease 2019 (COVID-19) illicit strong humoral and cellular responses and have high efficacy for preventing and reducing the risk of severe illness from COVID-19. Since solid organ transplant (SOT) recipients were excluded from the phase 3 trials, the efficacy of the COVID-19 vaccine remains unknown. Understanding the serological responses to COVID vaccines among SOT recipients is essential to better understand vaccine protection for this vulnerable population. Methods. In this prospective cohort study, a subset of SOT recipients who were part of our center's larger antibody study were enrolled prior to receipt of two doses of the BNT162b2 (Pfizer, Inc) vaccine for high resolution immunophenotyping. To date, plasma has been collected for 10 participants on the day of their first dose (baseline), day of their second dose, and 28 days post second dose. 23 healthy participants planning to receive either BNT162b2 or mRNA-1273 (ModernaTX, Inc) were also enrolled, providing plasma at the same timepoints. Ultrasensitive single-molecule array (Simoa) assays were used to detect SARS-CoV-2 Spike (S), S1, receptor-binding domain (RBD) and Nucleocapsid (N) IgG antibodies. Results. Participant demographics and SOT recipient characteristics are summarized in Table 1. Low titers of anti-N IgG at all timepoints indicate no natural infection with COVID-19 during the study (Fig 1A). There were significantly lower magnitudes for anti-S (p< 0.0001), anti-S1 (p< 0.0001), and anti-RBD (p< 0.0001) IgG titers on the day of dose 2 and day 28 post second dose for SOT recipients compared to healthy controls (Fig 1B,C,D). Using the internally validated threshold of anti-S IgG >1.07 based on pre-pandemic controls, only 50% of the SOT sub-cohort responded to vaccine after series completion (Fig 2). There was a positive trend between months from transplant and anti-S IgG titer (Fig 3). Black error bars denote median and 95% CI. The dotted line on panel B denotes an internally validated cutoff of 1.07;anti-S IgG titers greater than 1.07 denote a positive response. SOT recipients further out from transplant tend to have a higher anti-S IgG response. The dotted line denotes an internally validated cutoff, with anti-S IgG titers greater than 1.07 indicating a positive response. Conclusion. SOT recipients had a significantly decreased humoral response to mRNA COVID-19 vaccines compared to the healthy cohort, with those further out from transplant more likely to respond. Further research is needed to evaluate T-cell responses and clinical efficacy to maximize the SARS-CoV-2 vaccine response among SOT recipients.

14.
Western Journal of Emergency Medicine ; 23(1.1):S25-S26, 2022.
Article in English | EMBASE | ID: covidwho-1743912

ABSTRACT

Learning Objectives: To elucidate the frequency of physician misidentification in the ED and evaluate whether a low-cost intervention can help reduce rates and improve overall physician wellness using an observational study. Background: Multiple studies have shown that only a small fraction of patients are able to identify their physician. Physician misidentification impacts patient care, patient satisfaction, and physician wellbeing. Objectives: Our study aims to evaluate whether the incorporation of “DOCTOR” badges can improve identification and the overall wellness of EM physicians. We hypothesize that the rate of EM physician misidentification would be more frequent among female physicians and that badges can be a low-cost tool to rectify this problem. Methods: A voluntary anonymized survey was distributed to 83 EM residents and 28 EM Attendings working in a large urban academic center. All physicians were given a badge to wear and then were re-surveyed. Descriptive data are presented as means with standard deviation, percentages, and 95% confidence intervals. Mean rate of misidentification were compared pre and post “DOCTOR” badges using a Student's t-test. Results: Physician response rates and demographics are given in Table 1. 97% of female EM physicians are misidentified compared to 43% of male EM physicians 95% CI: [37,66], p<0.0001. After wearing the badges, there was a decrease in misidentification of female EM physicians to 81.6%, p=0.03 and 73.7% of female physicians reported feeling more valued vs 44.9% male physician 95% CI [7.9,46], p=0.007. Similarly, 64.3% EM physicians felt less frustration with misclassification, 81.6% female physicians vs. 51% male physicians, 95% CI [10.5,47], p=0.0033. Conclusions: Female EM physicians are disproportionately misidentified by patients and their families and are more likely to feel undervalued. We found that the use of “DOCTOR” badges decreased misidentification and improved wellness. Therefore, having EM physicians wear a “DOCTOR” badge may be an effective long-term solution. Reported efficacy may have been even higher as our study was partially limited by the COVID-19 pandemic when badges became obscured by PPE.

15.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326837

ABSTRACT

SARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of Experimentally-defined T cell epitopes derived from the non-spike Remainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I-V-);infected and non-vaccinated (I+V-);infected and then vaccinated (I+V+);and non-infected and vaccinated (I-V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV-2 correlates of protection.

16.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326825

ABSTRACT

Better methods to interrogate host-pathogen interactions during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections are imperative to help understand and prevent this disease. Here we implemented RNA-sequencing (RNA-seq) combined with the Oxford Nanopore Technologies (ONT) long-reads to measure differential host gene expression, transcript polyadenylation and isoform usage within various epithelial cell lines permissive and non-permissive for SARS-CoV-2 infection. SARS-CoV-2-infected and mock-infected Vero (African green monkey kidney epithelial cells), Calu-3 (human lung adenocarcinoma epithelial cells), Caco-2 (human colorectal adenocarcinoma epithelial cells) and A549 (human lung carcinoma epithelial cells) were analysed over time (0, 2, 24, 48 hours). Differential polyadenylation was found to occur in both infected Calu-3 and Vero cells during a late time point (48 hpi), with Gene Ontology (GO) terms such as viral transcription and translation shown to be significantly enriched in Calu-3 data. Poly(A) tails showed increased lengths in the majority of the differentially polyadenylated transcripts in Calu-3 and Vero cell lines (up to ~136 nt in mean poly(A) length, padj = 0.029). Of these genes, ribosomal protein genes such as RPS4X and RPS6 also showed downregulation in expression levels, suggesting the importance of ribosomal protein genes during infection. Furthermore, differential transcript usage was identified in Caco-2, Calu-3 and Vero cells, including transcripts of genes such as GSDMB and KPNA2, which have previously been implicated in SARS-CoV-2 infections. Overall, these results highlight the potential role of differential polyadenylation and transcript usage in host immune response or viral manipulation of host mechanisms during infection, and therefore, showcase the value of long-read sequencing in identifying less-explored host responses to disease.

17.
Gastroenterology ; 160(6):S-334-S-335, 2021.
Article in English | EMBASE | ID: covidwho-1598594

ABSTRACT

Background: Southern California Kaiser cares for 4.7 million patients of which thousands carry a diagnosis of Inflammatory Bowel Disease (IBD). As the SARS-COV2 Virus has rapidly become a worldwide pandemic that causes the deadly COVID-19 respiratory syndrome, particular attention has been paid to patients with chronic IBD, who often take immunosuppressive medications that pose greater infectious risk than those in the general population. Although recent international studies have not shown worsening outcomes among IBD patients with COVID 19, not much is known about the local, regional characteristics of this population. In this study, we aim to describe the characteristics of IBD patients in the Southern California Kaiser healthcare system who have been diagnosed with COVID-19. Methods: We retrospectively gathered data from the electronic medical records of adult IBD patients who carry an ICD-10 diagnosis of Ulcerative colitis (UC) or Crohns disease (CD) and who were also diagnosed with COVID-19 with a positive lab result and ICD 10 code between the dates of January 1, 2020 and October 31, 2020. We then tabulated descriptive data among non-hospitalized, hospitalized, and deceased patients of this population. This data was verified through manual chart review. Results: Among 13,262 patients with IBD, 475 cases with suspected COVID were obtained and 280 patients had a confirmed positive COVID-19 test on manual review (89 CD, 191 UC). Average age was 49 years old with a female predominance of 59%. 14%(n=39) of patients were hospitalized and 2.5% (n=7) died. The population was predominantly White (48%) and Hispanic (37.5%). 36% of patients were not on any IBD medications while 38.9% were on aminosalicylates, 21% were on biologic agents, 9.3% were on thiopurines, and 4.3% were on corticosteroids. Among the hospitalized patients, 67%(n=26) were admitted for COVID-19. Hospitalized patients had an average age of 61 years old, 51% were female, and had an average length of stay of 7.7 days. 56.4% (n=22) were not on any IBD medications, while 7.7% (n=3) were on corticosteroids, and 18% (n=7) were on biologic agents. Among patients that died, 71%(n=5) died of COVID-19 related complications and 14% (n=1) died of renal failure. None were on biologic agents and 71% (n=5) were not on any medications for IBD. Conclusion: This study did not show increased risk of mortality among patients with IBD who are on biologic therapy. Mortality rate is comparable to published data in patients without IBD. Overall, the diagnosis of COVID 19 was associated with patients that were predominantly women, White or Hispanic, and patients not on any medications for IBD. Further research will be conducted to analyze risk factors such as medical co-morbidities in this population. (Table Presented) (Table Presented) (Table Presented)

18.
Blood ; 138:184, 2021.
Article in English | EMBASE | ID: covidwho-1582407

ABSTRACT

Background: Early reports suggested that cancer patients have a 1.7-fold increased risk of contracting SARS-CoV-2 and higher rates of severe events and mortality compared with general population. Patients with hematologic malignancies may have worse COVID-19 outcomes, due to an impaired humoral immune response from their underlying malignancy and concurrent anticancer therapy. In this multi-center, retrospective, observational study, we evaluate the associations of COVID-19 outcomes with patient and lymphoma disease characteristics. Methods: EMRs at 10 study centers across the USA identified 519 patients with a diagnosis of lymphoma, CLL, or other lymphoid malignancies, who had a documented positive result of SARS-CoV-2 PCR or nucleocapsid antibody testing. Descriptive statistics were used to summarize the demographic and clinical characteristics. Logistic regression was used to evaluate the associations of individual characteristics with COVID-19 outcomes, adjusted for center (NYU vs. other). The interactions between each of the variables was also included in these models;since the interactions were generally small and non-significant, only the main effect of center was included. Two-sided p-values ≤0.05 were considered significant;there were no adjustments for multiple variables or endpoints. Each analysis was based on complete data for that analysis. Results: Tables 1 and 2 provide demographic and clinical characteristics, respectively, of the 519 patients. The mean age was 61.9 years, with 296 (57%) male and 374 (72%) white patients. NYU had the largest cohort (318 patients), with the remaining centers contributing a range of 3 to 69 patients (median 14). Logistic regression models for the association of each COVID-19 outcome with individual clinical and patient characteristics included adjustments for the center (NYU/other). While center effects were statistically significant, center by covariate interaction effects were not and are not included in the final models. The odds ratio (OR) estimates and p-values for each patient and CLL/lymphoma clinical variable are shown in Tables 3 and 4, respectively. The risks of experiencing a severe event, death, and hospital admission increased with age;for each 10 years of age increase, the ORs were 1.58 for experiencing severe events, 1.78 for death, and 1.65 for hospital admission. The risks of poor outcome were higher in males than in females (OR 1.93 for severe events, 1.85 for death, and 1.47 for hospital admission). Patients with Charlson Comorbidity Index (CCI) >5 had a higher risk of severe events (OR 2.46), mortality (3.30) and hospital admission (2.73) compared to patients with CCI ≤5. Compared to patients with HL, patients with aggressive NHL had a higher risk of severe events (OR 4.05), mortality (4.68) and hospital admission (4.65). Patients with CLL similarly had a higher risk of severe events (OR 4.64), mortality (4.65) and hospital admission (5.93) compared to HL patients. Patients with indolent NHL had a higher risk of hospital admission (OR 3.95) but not a higher risk of mortality compared to HL. Patients in remission at the time of COVID-19 diagnosis had a lower risk of severe events (OR 0.42), mortality (0.36) and hospital admission (0.40) relative to those who were not in remission. Patients who received cytotoxic chemotherapy within 28 days of their COVID-19 diagnosis had a higher risk of severe events (OR 2.54), mortality (2.79), and hospital admission (2.31). Patients who received an anti-CD20 monoclonal antibody within 6 months of COVID-19 diagnosis had a higher risk of severe events (OR 2.60), mortality (2.17) and hospital admission (3.28). Conclusions: In addition to demographic and comorbidity risk factors identified in previous studies, our study shows that patients with aggressive NHL and CLL, or patients who have received recent cytotoxic chemotherapy or anti-CD20 mAB, may be at risk for poor COVID-19 outcome. The difference in risk between NHL and HL patients is likely associated with young age of HL patients but may also be related o differences in underlying innate and adaptive immune defects. Patients at high risk for poor outcome should be a priority for studies of monoclonal antibody prophylaxis. If defects in humoral immunity are at the root of poor outcome, this may be compounded by poor response to vaccination. Multivariate analysis of this data will be completed in advance of the meeting. [Formula presented] Disclosures: Olszewski: Celldex Therapeutics: Research Funding;PrecisionBio: Research Funding;TG Therapeutics: Research Funding;Acrotech Pharma: Research Funding;Genentech, Inc.: Research Funding;Genmab: Research Funding. Barta: Daiichi Sankyo: Honoraria;Seagen: Honoraria;Acrotech: Honoraria;Kyowa Kirin: Honoraria. Hernandez-Ilizaliturri: AbbVie: Other: Advisory Boards;Incyte: Other: Advisory Boards;Celgene: Other: Advisory Boards;BMS: Other: Advisory Boards;Pharmacyclics: Other: Advisory Boards;Amgen: Other: Advisory Boards;Kite: Other: Advisory Boards;Gilead: Other: Advisory Boards;Epyzime: Other: Advisory Boards. Leslie: Janssen: Consultancy, Speakers Bureau;Merck: Consultancy;Abbvie: Consultancy, Honoraria;Epizyme: Consultancy, Honoraria, Speakers Bureau;PCYC/Janssen: Consultancy, Honoraria, Speakers Bureau;Seagen: Consultancy, Honoraria, Speakers Bureau;TG Therapeutics: Consultancy, Honoraria, Speakers Bureau;Celgene/BMS: Consultancy, Honoraria, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy;BeiGene: Consultancy, Honoraria, Speakers Bureau;Karyopharm Therapeutics: Honoraria, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;Pharmacyclics: Consultancy, Honoraria, Speakers Bureau. Diefenbach: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding;Morphosys: Consultancy, Honoraria, Research Funding;Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;Perlmutter Cancer Center at NYU Langone Health: Current Employment;Incyte: Research Funding;AbbVie: Research Funding;Trillium: Research Funding;IGM Biosciences: Research Funding;IMab: Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Gilead: Current equity holder in publicly-traded company;MEI: Consultancy, Research Funding;Celgene: Research Funding;Seattle Genetics: Consultancy, Honoraria, Research Funding.

19.
Journal of Immunology ; 206:1, 2021.
Article in English | Web of Science | ID: covidwho-1548244
20.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293076

ABSTRACT

COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, vaccine escape variants might arise leading to a re-emergence of COVID. In anticipation of such a scenario, the identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2- DOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in- line with reported proteinuria and liver damage in patients with COVID-19. We identified 35 drugs that reduced viral replication in Vero and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.

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