bluuebunny/crossref_metadata_2025_split huggingface dataset:
509. Comparision of CD4+ T Cells in Patients with Severe vs Critical COVID -19
Authors: Gomez-Gomez Brenda , Espinosa-Aguilar Luis , Garcia-Guerrero Javier , Hoyo-Ulloa Irma , Mendoza-Aguilar Raquel , Moreno-Sanchez Francisco , Acosta Benjamin Valente , Ontañon-Zurita Diego 
Published: January 2021

Abstract

Background
Over the past few years, it has been shown that T cells play an essential role in antiviral immunity, in the course of the COVID-19 pandemic some studies reported an association between lymphocytopenia and exhaustion of the surviving remaining T cells which are apparently functional in patients with acute COVID-19, specially in those with severe forms of presentation. Some studies have reported an association where less than 800 CD4 + T cells are negatively related to the survival of seriously ill patients with COVID -19.

Methods
We included 19 patients admitted to our hospital (ABC Medical Center) from May 7 to 15, 2020 with a confirmed diagnosis of COVID-19 and were randomized into 2 groups according to the severity of the presentation (severe or critical) A determination of CD4 + T cells was made at admission, we also reported the need for invasive mechanical ventilation at some point of the hospitalization for each group, all patients were followed until their hospital discharge. One patient was excluded because he was still admitted at the time of the analysis.

Results
Of the 18 patients included, 9 (50%) fulfilled criteria of severe and 9 (50%) of critical. The mean of CD4 + T cell was 455 (256–697) for the severe and 285.44 (145–430) for the critical (CI 95% P 0.46), the determination of CD8+ T cell was 212 (88–392) for the severe and 201 (59–534) for the critical (CI 95% P 1.19), of the critical patients 8 (88.9%) required invasive mechanical ventilation and only one non-invasive mechanical ventilation, while the severe patients only required support with supplemental oxygen by nasal cannula (9 (100%)).The mean lenght of hospitalization was 12.73 days (3–34) and all the patients survived until they were discharged home.

Conclusion
As it has been reported in some studies, the pathogenesis of SARS-CoV-2 infection in humans is associated with a reduction and functional exhaustion of T cells in patients with COVID-19.In this study we presume that lower levels of CD4+T cells can be associated with critical forms of COVID 19 as the majority of critical patients in our report had &lt; 300 CD4 +T cell count, while we need further studies with a greater number of patients and follow-up to establish reliable determinations, we propose than the levels of CD4+T cell count could be use as a good predictor of severity in COVID-19

Disclosures
All Authors: No reported disclosures
510. Elevated IL-1β level as a predictor of inflammation and death in COVID-19
Authors: Swartz Talia H , Gnjatic Sacha , Aberg Judith A , Merad Miriam , Sigel Keith 
Published: January 2021

Abstract

Background
SARS-Cov-2 (severe acute respiratory disease coronavirus 2) causes Coronavirus Disease 2019 (COVID19) and is associated with respiratory failure and death in severe disease. This is associated with high levels of cytokines such as IL-6, IL-8 and TNF-alpha which are predictors of severe outcomes. SARS-CoV-2 leads to activation of the NLRP3 inflammasome which results in secretion of the cytokine IL-1ß. While high levels of IL-1ß are not observed in most patients with severe COVID-19, there is a subset of patients with high IL-1ß levels. Here we sought to characterize these patients and determine whether high IL-1ß levels are associated with adverse outcomes and death in COVID-19.

Methods
We identified 90 patients with high IL-1ß levels (greater or equal to 2 pg/ml) and laboratory confirmed COVID-19 hospitalized in our hospital system in New York March 12 and May 8, 2020. We collected baseline clinical characteristics, laboratory values, COVID-19 treatment, and outcomes from this group and the group with IL-1ß levels below 2 pg/ml. Baseline clinical characteristics and outcomes were compared.

Results
Comparing patients by IL-1ß level had similar demographics (age, sex, race/ethnicity, smoking status and comorbid disease prevalence). The group had comparable levels of adverse markers of disease severity but the patients with high IL-1ß had increased inflammatory biomarkers including IL-8 (629 vs. 68 pg/ml, p&lt; 0.0001), TNF-alpha (30 vs. 51 pg/ml, p&lt; 0.0001), IL-6 (173 vs. 5075 pg/ml, p&lt; 0.0001), CRP (141 vs. 178, p=0.0007), d-dimer (2.6 vs. 4 p=0.0002), and increased rates of death (30% vs. 20%, p=0.008).

Conclusion
Demographic and comorbid conditions are not effective at predicting high IL-1ß serum levels in COVID-19 patients, however those individuals with high levels are at risk for adverse outcomes of severe disease and death. Further investigation is required to probe the mechanism of NLRP3 inflammasome activation and IL-1ß signaling and the role of this cytokine in mediated inflammation and death in COVID-19.

Disclosures
Judith A. Aberg, MD, Theratechnology (Consultant)
512. Kinetics of SARS-CoV-2 IgG responses among hospitalized patients with COVID-19
Authors: Beenhouwer David O , Chintalacharuvu Koteswara , Winnett Alexander , Goldin Evan , Bhattacharya Debika , Graber Christopher J , Goetz Matthew B , Fulcher Jennifer A 
Published: January 2021

Abstract

Background
The kinetics of antibody responses to SARS-CoV-2 infection are not fully understood. We analyzed IgG responses to the SARS-CoV-2 Spike protein receptor binding domain (RBD) in COVID-19 patients admitted to VA Greater Los Angeles (VAGLA) and correlated with clinical outcomes.

Methods
Serially admitted patients from March 20-May 10, 2020 with at least one available residual serum specimen were included in this analysis. Serum samples selected for analysis included first, last, and intermediaries spaced ≥ 5 days apart, as available. Anti-RBD IgG was detected with an enzyme immunoassay (EIA) using recombinant RBD protein. Serum from an uninfected individual collected April 2019 was used as control. The average optical density of the control in triplicate plus 3 standard deviations was considered the threshold positive/negative value. The highest dilution above the threshold value was considered the IgG titer. Clinical groups were defined as asymptomatic, moderate/severe (no ICU) or critical (mechanical ventilation, cytokine storm and/or death).

Results
Of the 43 consecutive patients admitted to VAGLA with COVID-19 in this analysis, 40 developed detectable RBD IgG responses with maximum inverse titers (MIT) ranging 100-819,200, geometric mean 12,152. Five patients remained asymptomatic but had positive EIAs with median MIT 3200 (IQR 800–3200). Twenty-five had moderate-severe illness with median MIT 25600 (IQR 6400–102400). Ten patients with critical disease had median MIT 38400 (IQR 8800–51200). The median time to positive IgG was 10 days for asymptomatic (IQR 10,10), 4 days for moderate-severe (IQR 3,15), and 7 days for critical (IQR 3.5,14.5). The figure depicts RBD IgG titers over time after onset of symptoms. Asymptomatic patients had a more gradual rate of increase and lower peak titers, while critical patients had the fastest rate of rise and the highest peak titers. Of the 21 patients with samples &gt; 30 days after symptom onset (range 31–67 days), there was no evidence for decrease in anti-RBD IgG.
Kinetics of IgG to SARS-CoV-2 receptor binding domain by clinical severity

Conclusion
Following infection with SARS-CoV-2, disease severity correlates with both the rate of increase and peak in antibody titers. Anti-RBD IgG titers did not decrease over the observation period.

Disclosures
All Authors: No reported disclosures
519. Immune responses and COVID-19 severity
Authors: salvatore mirella , Vorkas Charles K , Sing Harjot , Morales Ayana , Soave Rosemary , Kapatia Shashi , Ellsworth Grant , Saito Kotha , Brown Christopher D , Hsu Jing-Mei , Casano Joseph , Inghirami Giorgio 
Published: January 2021

Abstract

Background
The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to &gt;200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear.

Methods
To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method.

Results
We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing.

Conclusion
The characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention.

Disclosures
All Authors: No reported disclosures
522. The Simple and Novel SAS Score to Predict Mortality at Presentation in 2541 Hospitalized COVID-19 Patients
Authors: Acosta Tommy J Parraga , Vahia Amit T , Chaudhry Zohra S , Gudipati Smitha , Arshad Samia , Ramesh Mayur , Zervos Marcus , Alangaden George J 
Published: January 2021

Abstract

Background
The clinical spectrum of the novel corona virus disease 2019 (COVID-19) ranges from mild to severe disease and death. We aim to construct a simple and novel scoring model that will predict mortality events in hospitalized COVID-19 patients.

Methods
We established a retrospective cohort of 2541 patients admitted with COVID-19 from February 19, 2020 to April 28, 2020 to Henry Ford Health System, MI. Sociodemographic data, comorbidities, and clinical data were collected. Our novel SAS score was constructed using 3 easily available parameters, namely Sex, Age, and Oxygen Saturation at presentation (Table 1 and 2). Primary endpoint was mortality. Multivariate analysis with logistic regression was done and the model was assessed using receiver operating characteristic (ROC) with area under ROC (AUROC) to determine the optimal cutoff for sensitivity, specificity, and positive and negative predictive values.

Results
The mean age of survivors was 61 compared to 75 years for non-survivors (standard deviation 16 vs 13.8, p&lt; 0.0001), and 1298 (51.1%) were men. Multivariate analysis of the SAS score adjusted for modified SOFA [Sequential organ failure assessment] score (mSOFA) showed that age (odds ratio [OR] 2.4, 95% confidence interval {CI} 2.04–2.72, p&lt; 0.0001) and oxygen saturation (OR 1.6, 95% CI 1.27–1.98) were the most significant predictors of mortality in the model. The SAS score had an AUROC of 0.78 (95% CI 0.77–0.81) (Figure 1). A cutoff score of 3 offered the most sensitivity for predicting mortality while maintaining a negative predictive value of 95% (Table 3). Comparison of AUROC shows that SAS score adjusted to mSOFA has better diagnostic information compared to either SAS score or mSOFA alone (Figure 2).

Conclusion
The easy to use SAS score at time of presentation identified hospitalized COVID-19 patients at high risk for mortality. Application of the SAS score in the emergency department may help triage patients to inpatient versus outpatient care.

Disclosures
Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support)
524. COVID 19 Infection in Pregnant Women and Newborn Infants at a Single U.S. Center: What Disparities, Testing and Isolation Practices can Teach Us
Authors: Camelo ingrid Y , Figueira Marisol , Sabharwal Vishakha 
Published: January 2021

Abstract

Background
COVID-19 transmission from mother to infant suggests that vertical and horizontal transmission of COVID-19 are possible. Here we describe the demographic and clinical characteristics and outcomes of SARS-CoV-2 positive pregnant women and their newborns.
Summarized Characteristics of 19 COVID-19 Positive Mothers that Delivered 3/31/20–6/17/20 at Boston Medical Center

Methods
We collected data from the electronic medical records of pregnant women. Data composed of maternal demographics and morbidities, and symptoms of COVID-19. Descriptive statistics were used to analyze data. Women had positive polymerase chain reaction (PCR) testing done by nasopharyngeal swabs.
Each newborn was tested for SARS_CoV-2 by RT_PCR with a nasopharyngeal swab at 24 hours, 48 hours, and day 5 of life.

Results
36 women met criteria to be included in this study. 22% had chronic hypertension, 8% had asthma, one had chronic HIV and hepatitis C, 30% had pregnancy-related morbidities including pregnancy-induced hypertension (19%), cholestasis of pregnancy (8%) and gestational diabetes(3%) (Table1) Of the 32 deliveries to date, 17 (53% delivered vaginally and 15 (47%) via C-section. Of the 15 C-sections, 6 (40%) were due to complications related to COVID-19. 38% (14/36) women developed hypoxia.
Five newborns (15%) born to SARS-CoV-2 positive mothers had positive PCR testing for SARS-CoV-2. 2 of them were born prematurely and by C section secondary to COVID 19 infection respiratory deterioration. One premature infant tested positive for RT-PCR for SARS-CoV-2 on days 1, 2, and 5. The other one was positive on day 2. The two full-term newborns who tested positive by PCR for COVID 19 after delivery, were not delivered secondary to COVID 19 complications. One infant who was separated from his mother was negative by PCR at days 1,2 and 5 but tested positive later after being in contact with his mother.

Conclusion
Our population of pregnant mothers had a high incidence of cesarean section secondary to COVID 19 infection complications. They also had a high frequency of chronic health conditions.
Infants born to mothers with COVID-19 can have positive PCR tests for SARS-CoV-2 suggesting that both, vertical and horizontal mother to infant transmission is possible. Infants had negative tests before positive tests, suggesting false negative testing may have occurred.

Disclosures
All Authors: No reported disclosures
527. Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
Authors: Psevdos George , Papamanoli Aikaterini , Lobo Zeena 
Published: January 2021

Abstract

Background
The area of New York was hit hard by the COVID 19 pandemic with Suffolk county in Long Island numbering &gt;40 thousand cases and 1900 deaths by the end of May 2020. The Veterans Affairs Medical Center (VAMC) at Northport NY serves over 30000 Veterans. We report our institution’s experience during the COVID 19 outbreak

Methods
Retrospective chart review of hospitalized Veterans (VETS) with COVID-19 from March 1st to May 31st 2020 at Northport VAMC

Results
A total of 141 VETS had laboratory confirmed SARS-CoV-2 infection, 67 got hospitalized, and 20/67 died. The median age of the hospitalized cohort was 73 years (33 to 94). Figure 1 shows the dates of tests, Tables 1 &2 summarize the demographic characteristics, medical history and laboratory findings. No co-infection with influenza or other respiratory viruses were identified. The deceased group was older 77.5 vs 71 years P 0.007, had lower oxygen saturation and higher respiratory rate on presentation, had longer length of stay P 0.091, more likely to be in ICU and intubated, had lower bicarbonate levels, higher SAPS P &lt; 0.001, higher lactate dehydrogenase, blood urea nitrogen, potassium levels, and higher peak procalcitonin, CRP, ferritin, ESR levels. There was no difference between recovered and deceased in terms of comorbidities except atrial fibrillation. Also, no difference in use of ACE inhibitors, statins, famotidine, hydroxychloroquine (HCQ), azithromycin, doxycycline, steroids. Beta lactam antibiotics and tocilizumab were given more in the deceased group. HCQ was stopped in 1 patient due to QTc prolongation. No bacteremia identified in the recovered group contrary to two occasions in the deceased, E. faecalis and S. mitis. Six pneumonias in intubated deceased patients were identified (3 had received steroids and one tocilizumab) and 4 in recovered (2 intubated/steroids and 1 tocilizumab). 12 recovered patients had persistent positive nasopharyngeal PCR for SARS-CoV-2 for average 29 days (14 to 79 days), and 4 of them were checked and had detectable IgG antibody
Dates of Tests for Hospitalized Veterans with COVID-19

Comparison of Demographic Data and Comorbidities in Recovered vs Diseased Hospitalized Veterans with COVID - 19

Comparison of Laboratory Data in Recovered vs Diseased Hospitalized Veterans with COVID - 19

Conclusion
The inpatient mortality of hospitalized VETS with COVID-19 in our institution was 30%. Mortality was associated with older age. Ongoing monitoring of outcomes in hospitalized patients will be important to understand the evolving epidemiology of COVID-19 among US VETS.

Disclosures
All Authors: No reported disclosures
529. COVID-19 Antibody Responses in Solid Organ Transplant Recipients
Authors: Zervou Fainareti , Ali Nicole , Neumann Henry J , Madan Rebecca Pellett , Mehta Sapna A 
Published: January 2021

Abstract

Background
Studies to date indicate that most adults develop IgG antibody to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 6 weeks of COVID-19 symptom onset. The seroconversion rate of solid organ transplant recipients (SOTR) following COVID-19 is unknown. Elucidation of humoral immune responses following COVID-19 in SOTR may inform risk of reinfection and the development of safe and effective vaccines for immunocompromised hosts.

Methods
We assessed the frequency of SARS-CoV-2 IgG detection among adult SOTR diagnosed with COVID-19 by nasopharyngeal PCR assays between 3/1/2020 and 6/5/2020. SARS-CoV-2 IgG was detected in serum using the Abbott IgG assay at the manufacturer’s recommended cut-off. Our primary objective was the frequency of SARS-CoV-2 IgG seropositivity after COVID-19. A secondary objective was to identify clinical factors associated with seroconversion. The mean age and nadir absolute lymphocyte count (ALC) were calculated between seropositive and negative SOTR and compared by Student’s t-test.

Results
Among 93 SOTR diagnosed with COVID-19, 19 died before SARS-CoV-2 IgG testing could be performed, and 18 had testing pending as of abstract submission. 56 SOTR (44 kidney, 5 heart, 4 liver, 1 lung, and 1 heart-kidney recipients) completed testing and were included in the analysis. Median age was 58 years (IQR 49.5–67), and all received maintenance immunosuppression at the time of COVID-19 diagnosis with median nadir ALC during illness of 400 (IQR 200–600). SARS-CoV-2 IgG testing was performed at a median of 60 days (IQR 50–70) from symptom onset, the shortest interval being 16 days. 47 out of 56 SOTR tested positive for SARS-CoV-2 IgG. The likelihood of seroconversion was not different between those who were tested at &lt; or ≥ 60 days from symptom onset (p=0.26), nor did it vary significantly by age (p =0.59), gender (p=0.53) or nadir ALC (p =0.28).

Conclusion
83% of evaluated SOTR with COVID-19 disease had detectable SARS-CoV-2 IgG in serum at a median of 60 days after symptom onset. Studies are ongoing to identify variables associated with poor antibody response among the nearly 20% of SOTR in this cohort who failed to seroconvert. The significance of seroconversion on risk of reinfection and vaccine immunogenicity remains to be determined.

Disclosures
All Authors: No reported disclosures
531. COVID-19 infection outcome in African American Renal Transplant recipients: Detroit Medical Center experience
Authors: Cruz Angela Beatriz V , Tejada Claudia Jarrin , Zachariah Mareena , Hussein Shakir , Wilpula Elizabeth , Meeks Nicole , Wolff Jeffrey A , Chandrasekar Pranatharthi 
Published: January 2021

Abstract

Background
Transplant recipients are more vulnerable to infections including COVID-19, given their co-morbidities and chronic immunosuppression. Most preliminary care series report rapid clinical progression and higher mortality compared to the general population.

Methods
Retrospective study at Harper University Hospital - Detroit Medical Center. Twenty-five renal transplant recipients (RTR) presenting consecutively with COVID-19 symptoms and positive NP swab PCR for SARS-CoV2 between 03/01/2020 - 05/01/2020 were included. Data on demographics, clinical presentation, laboratory findings, management and outcomes were collected.

Results
All 25 patients were hospitalized. Patients had a median age of 56, all African American and deceased donor transplant recipients. Most had hypertension (96%), about half (52%) had diabetes, 64% had pulmonary disease including obstructive sleep apnea, COPD and pulmonary hypertension. Most common presenting symptom was dyspnea (64%), followed by fever and cough (56%) and diarrhea (56%). One-half of patients had multifocal opacities on initial chest x-ray (52%). Immunosuppression with tacrolimus and low dose prednisone was continued, while mycophenolate mofetil was held on admission. Following institution guidelines, hydroxychloroquine was given to 32%, while 48% received both hydroxychloroquine and steroids. Prophylactic anticoagulation was given to 80% of patients and therapeutic coagulation to 8%. Oxygen supplementation given to 60% of patients and one patient required intubation. Three patients (12%) required transfer to the intensive care unit, one expired. At follow-up, treatment with mycophenolate was reintroduced based on resolution of symptoms and laboratory parameters.

Conclusion
COVID-19 infected RTR in this small cohort had lower mortality of 4% (n=1) compared to State-wide mortality of 10%. Despite multiple co-morbidities and chronic immunosuppression, our patient cohort had excellent prognosis and lower mortality compared to other series. Exact reasons for this optimal outcome are explored.

Disclosures
All Authors: No reported disclosures