Examining the Causes of Maternal Mortality in Pregnant Women Since the Beginning of the COVID-19 Pandemic in Hamadan Province, Western Iran: A Research Article

Background: Maternal mortality prevention and delivering optimal outcomes for both mother and fetus is the utmost concern of health systems in any country. Objective(s): This study aimed to examine maternal mortality in pregnant women since the beginning of the COVID-19 pandemic in Hamadan province, western Iran. Examining the causes of maternal mortality can be valuable in identifying mortality factors in line with prospective strategic plans. Method(s): This case series study introduces the data of seven deceased pregnant women, the deaths of whom occurred since the beginning of the COVID-19 pandemic (December 2019 - March 2021) in the hospitals of cities within Hamadan province. All data were reported at the time of death or at least 14 days after hospital admission. In this study, epidemiological features and pregnancy history, background dis-eases, clinical symptoms, initial vital signs, medications in use, clinical laboratory values, delivery type, and neonatal outcome were assessed, respectively. Result(s): In the seven maternal mortality cases reported in this study, three women succumbed to pregnan-cy-related causes (two cases of preeclampsia and one case of antiphospholipid syndrome), and four women to severe coronavirus disease. All deceased mothers had been admitted to the intensive care unit as a result of severe illness. Four cases concerned a background condition as well, which included thrombo-embolic disorders, epilepsy, and lupus. In mortality cases, two women displayed a BMI score over 30. One maternal death had occurred 42 days postpartum, while five deaths had occurred prior to 37 weeks of gestation, and one past 37 weeks of gestation. Conclusion(s): This report provided valuable information on maternal mortality factors. Maternal mortality necessitates a careful acquisition of monitoring data, but in the prevailing pandemic circumstances, cau-tion necessitates raising awareness of the maternal mortality potential in women with COVID-19 diagnosis in the second or third trimester. Pregnancy care programs must focus on recognizing high-risk groups of mothers-to-be with background conditions and risk factors for pregnancy, given that early diagnosis and prompt referral are invaluable in the immediate treatment and relief of pregnant mothers-to-be.Copyright © 2022 Bentham Science Publishers.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world. © 2022 The Authors

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Summary Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants’ family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

The Evolution of Mortality in Kidney Transplant Recipients at a Single Center in the Era of Covid

Purpose: Mortality secondary to COVID-19 infection is significantly higher in solid organ transplant recipients compared to the general population. Limited data exists evaluating the impact COVID has had on mortality compared to other causes, with even less data specific to the Mountain West region of the United States. This quality improvement project seeks to evaluate trends in patient mortality at a center in the Mountain West region before and after the COVID pandemic in kidney transplant recipients (KTR). Method(s): This is a retrospective single-center analysis of all adult KTRs who underwent transplant between January 1999 and July 2021 and subsequently died between January 2015 and July 2021, assessing the change in mortality trends with the advent of the COVID-19 pandemic. Additional endpoints include time from transplant to death, graft status at time of death, and COVID vaccination status. Data collection included UNOS data reports as well as manual electronic medical record review. Result(s): One-hundred and seventy-two KTRs were included with baseline characteristics described in Table 1. Prior to the COVID-19 pandemic, the most common etiology of mortality was cardiovascular cause with a median of 18% mortality (see Table 1). Of those who died in 2020, 33% were secondary to COVID-19 leading to a 174% increase in cumulative patient deaths compared to the year prior (23 vs 40 patient deaths in 2019 vs 2020;see Table 1 and Figure 1). Of those who died secondary to COVID, none had received the COVID-19 vaccine. Conclusion(s): COVID-19 pneumonia and its associated complications have led to an increase in and earlier mortality prior to vaccination implementation, changing the mortality landscape in KTRs. Further investigation is needed to elucidate non- COVID related changes in mortality and patient outcomes in the ongoing COVID pandemic.

CAUSES OF DEATH AMONG MEDICAL ICU (MICU) PATIENTS WITH PNEUMONIA DUE TO COVID-19 IN A SAFETY NET HOSPITAL

SESSION TITLE: Studies on COVID-19 Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: COVID-19 infection has a wide spectrum of clinical presentation ranging from asymptomatic carriers to severe critical illness associated with high morbidity and mortality. Although severe COVID-19 disease is associated primarily with pulmonary dysfunction and hypoxemia, many patients with lung disease can be supported by invasive mechanical ventilation allowing for other causes or complications to be the primary factor leading to death. The contribution of pulmonary dysfunction to the primary cause of death is not well-described. METHODS: We performed a retrospective cohort study of adult patients (age ≥ 18 years) admitted to the MICU at Los Angeles County + University of Southern California (LAC + USC) hospital from April 2020 to December 2020 with a primary diagnosis of COVID-19 pneumonia associated with documented in-hospital death. Data including baseline patient characteristics, primary cause of death and/or circumstance prior to withdrawal of care, and disease course were collected. The primary organ system responsible for death was defined as the organ dysfunction that most directly resulted in the patient’s death or impacted the decision for withdrawal of life support with details adapted from Ketcham, et al (Crit Care, 2020). RESULTS: We identified 86 patients who were admitted to the ICU that met inclusion criteria for review, of which 75% were male and 93% were Latino/Hispanic. Mean age on admission was 64 years. Of the 86 patients, 47 (54%) died from a primary pulmonary cause, 28 (32%) died from sepsis, 5 (6%) died from neurologic causes, and 4 (5%) died from either renal or hemorrhagic causes. Of the 47 patients who died primarily from pulmonary causes, 34 (72%) died from hypoxemic respiratory failure, 8 (17%) died from hypercapnic respiratory failure, and 5 (11%) died from combined respiratory failure. Of the 28 patients who died primarily from sepsis, 13 (46%) died from pneumonia, 7 (25%) died from fungemia, and 3 (11%) died from bacteremia with an identified source. Overall, 58 (67%) patients had multi-organ failure at time of death. Mean time from symptom onset to death was 27 days. Of the 69 patients who were intubated, mean times from admission to intubation and intubation to death was 4 and 19 days respectively. Only 1 patient who died underwent tracheostomy. CONCLUSIONS: We found that pulmonary dysfunction was the primary cause of death in the first year of the pandemic in our patient population at our single center MICU. Future studies are needed to further evaluate the primary cause of death in COVID-19 infection throughout the pandemic as medical management evolved and virus variant changed with time. CLINICAL IMPLICATIONS: Our study confirmed that a majority of patients with severe COVID-19 pneumonia died from hypoxemic respiratory failure. Further studies regarding COVID-19 interventions should focus on therapies to improve oxygenation. DISCLOSURES: No relevant relationships by Christopher Do No relevant relationships by Luis Huerta No relevant relationships by Janice Liebler

CONTINUES REMOTE CARDIAC MONITORING IN CRITICALLY ILL COVID-19 PATIENTS (C3 STUDY)

Objective: 1. To evaluate the use of remote cardiac monitoring of critically ill COVID-19 patients. 2. To correlate DOZEE early warning score(DEWS) with severity and outcome Design and method: Ballistocardiography (BCG)Ballistocardiography is a noninvasive method based on the measurement of the body motion generated by the ejection of the blood at each cardiac cycle. It also contains motion arising from breathing, snoring and body movements. Dozee Early Warning System (DEWS): DEWS is an overall score for risk assessment of the physiological status of a person. It is a cumulative score of risk levels of physiological parameters like HR,RR and SPo2, which acts as an early predictor for possible physiological decline. Assessment of severity of of Acute-illness Detection of clinical deterioration Initiation of a timely and competent clinical response Total 39 subjects were observed where 24 of the subjects were Male and 15 Female and the average duration of stay at the hospital was 5 days. There were 20 patients who had comorbid conditions like HYPOTHYROID, NHL,ASTHMA etc. 19 patients did not present with any co morbidities. The outcome of 10 patients was death and 29 patients were discharged after recovery, as reported by the healthcare professionals at the ward. The vitals of the subjects were continuously monitored by Dozee, a contactless remote patient monitoring system enabled with Dozee Early Warning System (DEWS) which reflects the overall patient condition based on the Respiration, Heart Rate and Spo2 of the patients. Results: The data from the continuous monitoring of the respiration rate, heart rate and oxygen saturation of the 39 patients were analysed for their duration of stay at the hospital. The DEWS score of the patients were also analysed Conclusions: It was concluded that continuous vitals monitoring of the patients and the resulting Dews scores were an indicator of the improving or deteriorating condition of the patients. The discharged patients showed a decrease in the DEWS score, especially Breathing DEWS before they recovered. However, the expired patients showed steady increase or a stagnant high Breathing dews until time of death.

Association Between Availability of ECMO and Mortality in COVID-19 Patients Eligible for ECMO: A Natural Experiment

RATIONALE: The outcomes of patients with COVID-19 who are medically eligible to receive ECMO, but do not because of limited health system capacity, have not been reported. METHODS: We analyzed prospectively collected clinical data from consecutive patients with SARS-CoV-2 referred for ECMO to a single center between January 1, 2021 and August 31, 2021. Each patient underwent a systematic assessment of medical eligibility to receive ECMO followed by a separate assessment of the health system's resources to provide ECMO. When health system resources were available, the patient was transferred to an ECMO center. When health system resources were not available, the patient was not transferred to an ECMO center and did not receive ECMO. Patients were followed until the time of death or hospital discharge. Among medically eligible patients, we compared those for whom health system capacity permitted transfer to receive ECMO to those for whom health system capacity did not permit transfer to receive ECMO with regard to the primary outcome of all-cause in-hospital mortality using Cox proportional hazards regression analysis adjusting for age, acute kidney injury, and receipt of vasopressors. RESULTS: Among the 240 patients with COVID-19 referred for ECMO, 90 patients (37.5%) were determined to be medically eligible to receive ECMO and were included in this study. Median age was 40 years (IQR, 34-48). The health system capacity to provide ECMO was available for 35 patients (38.9%), of whom 32 received ECMO and 3 died or developed a contraindication to ECMO after transfer but prior to cannulation. Death before hospital discharge occurred in 15 of the 35 patients (42.9%) for whom health system capacity permitted transfer to receive ECMO compared with 49 of the 55 patients (89.1%) for whom health system capacity did not permit transfer to receive ECMO (adjusted hazard ratio 0.23;95% confidence interval, 0.12 to 0.43;P < 0.001) (Figure 1). CONCLUSIONS: In this cohort of adults with COVID-19, nearly 90% of patients who were eligible for ECMO but did not receive it due to limited health system resources died before hospital discharge, despite young age and limited comorbidities. Periods of resource limitation during which provision of ECMO is determined by resource availability and not patient characteristics may act as a natural experiment, and these results suggest that ECMO provides a significant mortality benefit in the treatment of COVID- 19.

Detection of SARS-CoV-2 within enteric neurons and in brain

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, are increasingly recognised. Through immunohistochemistry against the SARS-CoV-2 nucleocapsid protein (NP), we aimed to characterise the multisystem viral tropism of SARS-CoV-2. FFPE tissue was obtained from 16 PCR-confirmed post-mortem COVID cases. Of these cases, 10 were full-body, 5 were brain only and 1 was a brain biopsy. Brain regions studied included frontal cortex, medulla, cerebellum, pons and olfactory bulb. Neurological symptoms featured in the cohort included brainstem encephalitis, acute disseminated encephalomyelitis (ADEM) and brain infarction. Immunohistochemistry of digestive system tissues revealed presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE-2 expression, the entry receptor for SARS-CoV-2 and one of the earliest affected cells in Parkinson's disease (PD). Within the brain, staining was widespread in all sampled regions but limited to endothelial cells only (including in the olfactory bulb). Furthermore, in the full-body post-mortem cases, positivity in brain endothelia was restricted to cases exhibiting multiorgan tissue positivity (3/9 cases). The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days vs mean = 20.3 days, p = 0.0416) suggesting NP detection was confined to the infectious period. Together, our findings provide evidence for enteric nervous system but not brain neuroinvasion of SARS-CoV-2 as well as potential insights into long-term complications of COVID-19 and PD pathogenesis.

Pathologic Features of Post-Acute Sequelae of COVID-19 (PASC) at Autopsy

Background: Across the globe, cases of post-acute sequelae of COVID-19 (PASC) are characterized by the delayed effects of SARS-CoV-2 infection in multiple organ systems. Patients may have appeared to recover from the initial infection, but experience sequelae of the disease weeks to months later. Autopsy studies of PASC have only initially begun. Our research aims to compare the pathology of cases in which patients experienced a prolonged, progressive decline, to the cases of patients who recovered from the initial infection of SARS-CoV-2, but experienced sequelae of the condition numerous weeks to months later. Design: Autopsies were performed on 17 male and female decedents with an age range of 31-79 years with cause of death related to COVID-19 infection confirmed by SARS-CoV-2 PCR, and time between the onset of symptoms and death ranging from 30 to 112 days. Cases in which the time between the onset of symptoms and death exceeded 30 days, with evidence of initial recovery, were considered potentially PASC-related. The cases were separated into two groups based upon the timeline of first positive PCR to time of death: those who succumbed to the initial COVID-19 infection after an extended hospital course, and those with potential PASC-related disease. Clinical, gross and microscopic findings from both groups were compared, as well as PCR and IHC for SARS-CoV-2 at autopsy. Results: The most common clinical comorbidity seen in both groups was hypertension (85.7%), followed by obesity and diabetes. Common microscopic findings in the lungs included proliferative to organizing diffuse alveolar damage (DAD). Findings in PASC-related cases included extensive alveolar fibrosis, fibrosing organizing pneumonia, and thrombi within medium-sized blood vessels. Two patients in their 30s presented with vasculitis/endotheliitis involving small blood vessels of the lungs and heart, consistent with Multisystem Inflammatory Syndrome. Additionally, late thrombotic events, and cardiac inflammation including macrophage infiltration appeared to be present in cases of PASC. Immunostaining for SARS-CoV-2 nucleocapsid and PCR at the time of autopsy did not reveal a persistence of virus in cases attributed to PASC. Figure 1 - 7 Conclusions: Our findings suggest that there may be pathologic differences between a prolonged course of acute COVID-19, and PASC-related disease. Characteristics of PASC included evidence of new or continued small vessel inflammation, macrophage infiltration, and/or fibrotic disease of affected organs.

Diurnal Variation in the Mortality of Patients with COVID-19 Pneumonia: A Retrospective Study

Introduction: Coronavirus Disease 2019 (COVID-19), the new contagious novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), pandemic in 2020-21 has had a devastating impact on human race. The most common cause of death among hospitalised patient was COVID-19 pneumonia or lung injury. Various studies have shown diurnal variation in human mortality due to all causes with or without intervention. Aim: To identify existence of diurnal variations for mortality among the hospitalised patients with COVID-19 pneumonia. Materials and Methods: This hospital-record based, retrospective study was conducted in a tertiary referral centre of north east India (Assam Medical College, Dibrugarh, Assam, India) which was a dedicated COVID-19 hospital during the pandemic. The study was conducted from September 2021 to December 2021 and the data was collected and recorded from the Cadaver slips issued to families of patient dying of COVID-19 pneumonia during the period January 2021 to August 2021. The data were generated by plotting the number of deaths of COVID-19 cases for each two hour interval as a percent of the mean number of deaths per two-hour interval and as a percentage of cumulative deaths per two-hour interval on a 24 hour scale. The deaths were sub grouped according to gender, age, and reported co-morbid causes of death along with pneumonia. Comparisons of data i.e., mean deaths/2 hour interval (mean±SD) were performed by one-way Analysis of Variance (ANOVA), followed by Bartlett's test for equal variances. The p-value <0.05 was considered as statistically significant. Results: Total 743 deaths, with 537 males and 206 females were included in the study. Mean age of the deaths was 56.39 years. There was rise of deaths during 4 PM to 6 PM (16:00 to 18:00) interval for all deaths due to COVID-19 pneumonia. The increase in deaths during this period was mainly due to deaths among males equal or above 65 years and females below age 65 years. However, the deaths of females equal or above the age of 65 years did not show significant diurnal variation. Only 26.51% (n=197) of pneumonia deaths were without co-morbidity. Conclusion: There exists a diurnal variation in mortality among COVID-19 pneumonia patients with evening rise of deaths. Diurnal variation is significantly more among males rather than females above 65 years.

Long-term outcomes of cancer patients infected with COVID-19

Background Patients with cancer appear to have poor outcomes with COVID-19 infection. Cohort analyses of short-term outcomes of COVID-19 (C19)-infected cancer patients (pts) have reported mortality rates ranging from 10 to 30%. Little is known about the long-term outcomes of cancer pts infected with C19. Here, we present an analysis of long-term outcomes of a cohort of active cancer pts with C19 infection. Methods This was a single center retrospective analysis of active cancer pts who tested positive for SARS-CoV-2 virus between 3/1/20- 9/30/20. Key inclusion criteria included a positive SARS-CoV-2 PCR test and an active cancer diagnosis within 90 days of a positive C19 test. We examined the rates of hospitalization for C19 infection, readmission, and C19-related mortality at 30-, 60-, 90-, and 120-day follow-up. Rates of persistent symptoms and systemic complications of C19 infection were described. Results We identified 81 active cancer pts with PCR-confirmed SARS-CoV-2 infection. Among this cohort, the median age was 55 years (range: 19- 89). 77% (N=62) had solid tumors and 23% (N=19) had a hematologic malignancy. 75% (N=61) were receiving an anti-cancer therapy at the time of C19 diagnosis. Median follow-up time from C19 diagnosis to last follow-up was 4.8 months (range: 0.1-9.0 mos). 32% (N=26) of the cohort required hospitalization for C19-related complications within 30 days of C19 diagnosis. Among those hospitalized, 35% (N=9/26) died from C19-related complications. Of the 17 pts who were discharged, 2 pts required readmission with a median time to readmission of 37 days. For these 2 pts, readmission was due to persistent dyspnea and hypoxia and both were treated for pneumonia with presumed bacterial superinfection. There were no additional hospitalizations for C19-related complications at 60-, 90-, and 120-day follow-up. At 90- day follow-up, 6 pts (7.4%) had been diagnosed with PE/DVT. No long-term cardiac, neurologic, or renal complications were observed. With regards to C19-related mortality, 30-day mortality was 8.6% (N=7) and 90-day mortality was 11.1% (N=9). No further C19-related deaths were observed after 90 days. All pts who died were hospitalized within 30 days of initial C19 diagnosis and remained hospitalized at the time of death. Persistent C19-related symptoms were noted in 8.2% (N=6/73) of the cohort at 60-days and 2.8% (N=2/71) at 90-day follow-up. Dyspnea was the most common symptom. Conclusions Among a cohort of active cancer pts with C19 infection, these data suggest that much of the morbidity and mortality associated with C19 infection appears to occur early, with decreased incidence of late complications beyond 30 days. Cancer pts who do not require hospitalization early in their infection course appear to have a decreased rate of late complications. Readmissions for C19-related complications were low, but this analysis was limited by a low number of pts. Achieving a better understanding of long-term outcomes of C19 pts with cancer will help us to better approach oncologic care as the pandemic continues.

Delayed Mortality among Solid Organ Transplant Recipients Hospitalized for Covid-19: An International Multicenter Study

Background. Studies of solid organ transplant recipients (SOTr) hospitalized for Covid-19 have focused on short-term outcomes with approximately 30 days of follow-up time. Intermediate-term mortality and associated risk factors for intermediate-term death have not previously been reported. Methods. Using data from a multi-center registry, we assessed mortality by 90 days among SOTr hospitalized for Covid-19 between 3/1/2020 and 12/31/2020. Multivariable Cox-proportional hazard models were used to compare risk factors for mortality by 28 and 90 days. Covariates were selected a priori based on known predictors of death in SOTr hospitalized for Covid-19. All patients were followed for 90 days or were censored at the time of death or last clinical contact, if this occurred prior to day 90 after diagnosis. Results. Among SOTr hospitalized for Covid-19, 198/979 (20%) died within 90 days of diagnosis and 37/198 (19%) of deaths occurred between days 29 and 90. Risk factors for mortality by day 90 days included age >65 years (1.8, 95% CI 1.3-2.4, P< 0.001), lung transplant (compared to non-lung) (1.6, 95% CI 1.1-2.4, P=0.02), chronic lung disease (2.2, 95% CI 1.5-3.4, P=0.002) and heart failure (1.9, 95% CI 1.2-2.9), which were similar to risk factors reported for 28-day mortality (Table 1). Diagnosis during the second half of 2020 (6/20-12/31/20) was associated with lower mortality by 28 days (aHR 0.7, 95% CI 0.5-1.0, P=0.03) compared to diagnosis during the early half of 2020 (3/1-6/19/20);however, mortality by 90 days was similar in the late and early time periods (aHR 0.9, 95% CI 0.7-1.2, P=0.54). Obesity and mTOR inhibitor use were also associated with death by 28 but not 90 days. Kaplan-Meier survival curves by time period of diagnosis are shown in Figure 1. Vertical tick marks represent censored cases. Early 2020 refers to cases diagnosed between March 1 and June 19, 2020 and late 2020 refers to cases diagnosed between June 20 and December 31, 2020. Conclusion. Approximately 20% of deaths among SOTr hospitalized for Covid-19 occurred between days 29 and 90. Future investigations are required to discern the mechanism(s) for the improvement in early, but not late, mortality among SOTr with Covid-19 during the course of the pandemic.

POSA393 Online Risk Calculator Using Machine Learning for Prediction of Survival After Hospital Discharge from COVID-19 Infection

Objectives: Predicting survival and risk of death after hospital discharge due to COVID-19 can help in screening patients who require special care after hospitalization. This study evaluates the survival curve and associated factors with mortality after COVID-19 admissions. Methods: Retrospective analysis until May 2021 from administrative database of 37,462 people. Analysis included 810 inpatients admitted with COVID-19 followed each month regarding survival after hospital discharge. Survival analysis performed using Cox Ridge Penalized Regression (CRPR), Gradient Boost Survival (GBS) and Random Survival Forest (RFS) from the Python library scikit-survival. Dataset separated into training and test set with the proportions of 75% and 25% respectively. Our predictive variables were patient’s age, sex, if had any comorbidity, cancer, hospitalization longer than 14 days or intensive care unit (ICU) stay. Results: From the 810 patients, 125 had died after hospital discharge, mean time of death 9.28 months. Model performance evaluated through the Concordance Index (C-Index) metric. CRPR had better performance with a C-Index of 0.74, while RFS and GBS had a C-Index of 0.73. Risk of death at any time during the follow-up period was significantly higher when presence of previous comorbidities (p=0.020), age greater than 60 years (p <0.001), ICU stay (p <0.001), and higher average length hospital stay (p=0.001). Conclusions: Several tools have been developed for to calculate absolute risk or chances of needing to go into hospital or dying from Covid-19. The online risk calculator that we developed is unique and suitable to predict which person present high risk of death after COVID-19 hospital discharges and prioritizing individuals to receive special care after leaving the hospital. Models like the one we have developed are only as good as the data they are trained on. We will update the calculator as the amount of data we are able to collect increases.

Pediatric post-mortem tissue donation during a pandemic: A model of collaboration

BACKGROUND: Obtaining post-mortem tissue from pediatric oncology patients is not only critical to research, but studies show that participating in the process can also help grieving families heal. Since 2019, the national Gift from a Child program a multi-institutional effort to increase the rate of rapid autopsies for pediatric CNS tumor patients has made significant progress. Collecting high-quality post-mortem tissue has advanced research through cell line generation and genomic analyses. Unfortunately, some autopsy programs temporarily shut down during the COVID-19 pandemic. METHODS: We retrospectively reviewed autopsies of four patients treated at Memorial Sloan Kettering (MSK) who underwent limited brain post-mortem examination at Weill Cornell Medicine College (WCMC) from June 2020 to June 2021. We collected patient demographics;DNR status;time of death and procedure;restrictions due to the COVID-19 pandemic;and results of the tissue analysis. Each case presented unique challenges and the timing of securing parental consent varied. RESULTS: Three of four specimens were processed within 12 hours of the time of death. Two Spanish-speaking families required interpreters services to obtain consent. In all cases tumor aliquots were flash frozen for further study. All specimens contained viable tumor and cell line generation was successful in one case All families/caregivers expressed gratitude for the opportunity to participate and for the handling of the procedures. DISCUSSION: Despite the sensitive nature of these cases, clinicians should offer the option of a rapid autopsy to caregivers of pediatric patients based on the scientific need and the positive effect it has on grieving families. This paper outlines the logistical efforts required for these donations to take place and provides a framework for providers to offer rapid autopsy as an option for families through this program.

COVID-19 in Children Following Hematopoietic Cell Transplantation: A Multinational Study of the European Bone Marrow Transplantation Society (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH)

Introduction COVID-19 is usually a mild disease in immunocompetent children, with ~1% requiring intensive care unit (ICU) admission and <0.1% mortality. Data on its course in children following hematopoietic cell transplantation (HCT) is limited. Methods Data on children following HCT who developed COVID-19 (diagnosed by positive SARS-CoV-2 PCR on respiratory tract samples) during 3.2020-4.2021 were prospectively collected by EBMT and GETH, including demography, HCT data, COVID-related manifestations, ICU admission and mortality. Factors associated with worse outcomes (ICU admission or mortality) were characterized. Results Sixty-two children (34 boys;median age 9;min-max;0.7-17 years) were reported from 27 centers, 16 countries;57 (92%) following allogeneic and 5 (8%) following autologous HCT. Underlying diseases were acute leukemia (23;37%), inherited disorders (9;15%), hemoglobinopathies (7;11%), solid tumor (6;10%), bone marrow failure (5;8%), other malignant (8;13%) and non-malignant (4;6%) diseases. Five (8%) children had high blood pressure;6 (10%) had underlying lung pathology. The median time from the most recent HCT to COVID was 5 months (min-max;0-169). The stem cell source was bone marrow (33);peripheral (22) or cord blood (1). Among the patients with information available, 34 (62%) underwent in-vivo T cell depletion, 20 (33%) received corticosteroids, and 36 (60%) other immunosuppressant drugs(s) within two months prior to and after the COVID-19 episode. The presence of acute grade 2-4 or chronic graft versus host disease (GVHD) was reported in 12/54 (23%) and 8/51 (16%) children, respectively. Clinical presentation (n=57) included fever (28;49%), cough (18;32%), diarrhea (8;14%), upper respiratory tract disease (as rhinorrhea, sinusitis, otitis, or pharyngitis;12;21%);six (10%) required oxygen to maintain oxygen saturation above 92%;20 children (35%) were asymptomatic. The median time from symptoms onset to COVID diagnosis was 1 day (-43-40). Sixty-three percent of patients were hospitalized;43% due to COVID. The proportion of children with neutropenia or lymphocytopenia (<500 cells/mm 3) was 75% and 73%, respectively. Sixteen children (26%) had evidence of viral (n=10), bacterial (n=6) or fungal (n=2) coinfections. The median time from COVID diagnosis to the last follow-up in alive patients was 69 days (min-max;2 - 294). Six (10%) children who developed COVID at a median 6.5 (min-max;2- 16) months following allo-HCT (median age 6 years;5 boys) required ICU care within a median 6 (min-max;-5-15) days after diagnosis. All of them were neutropenic, received steroids, and other immunosuppressive drugs at COVID diagnosis;5 had undergone in-vivo T cell depletion;5 were lymphocytopenic, 5 had GVHD (2 acute and 3 chronic);3 received non-invasive and 2 invasive ventilation. Three children had viral or bacterial coinfections. Three children died. Six (10%) children (5 boys, median age 10.5 years;min-max;4-13) who developed COVID at median 2 (min-max;0-147) months following allo-HCT died within median 35 days (min-max;5-54) after diagnosis. One had high blood pressure, and none suffered from underlying lung pathology. At the time of COVID, 3 were neutropenic, 2 lymphocytopenic;4 had GVHD (2 acute, 2 chronic);3 received steroids and 4 immunosuppressive drugs. Two had viral or bacterial coinfections. Five had positive SARS-CoV-2 PCR at the time of death. In 3, COVID was the primary cause of death. We compared nine children with the worse outcomes to 53 children with benign course. Among patients alive at 100-day post HCT, the probability of worse outcomes was higher in patients with vs. without chronic GVHD (Figure). No other significant differences were observed in demographic, underlying disease, and HCT-related characteristics. Compared to adults following HCT (Ljungman, Leukemia 2021), children had: - Shorter median time from HCT to COVID diagnosis, 5 vs 18 months;- Higher proportion of asymptomatic infections, 35% vs 9%;- Lower proportion of those who required oxygen, 10% vs 35%;- Lower all-cause mortality, 10% vs 29%. Conclusions Children following HCT with COVID-19 have a higher risk of ICU admission and mortality compared to immune competent children. The presence of chronic GVHD at COVID diagnosis was associated with worse outcomes. COVID course following HCT is milder in children compared to adults. [Formula presented] Disclosures: Averbuch: Takeda: Consultancy;Pfizer: Consultancy;GSK: Speakers Bureau. De La Camara: Roche: Consultancy;IQONE: Consultancy. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Mikulska: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Speakers Bureau;MSD: Speakers Bureau;Janssen: Speakers Bureau;Biotest: Speakers Bureau. Kulagin: Roche: Speakers Bureau;Sanofi: Speakers Bureau;Generium: Speakers Bureau;Biocad: Research Funding;Apellis: Research Funding;Alexion: Research Funding;X4 Pharmaceuticals: Research Funding;Novartis: Speakers Bureau;Johnson & Johnson: Speakers Bureau;Pfizer: Speakers Bureau. Cesaro: Sobi: Membership on an entity's Board of Directors or advisory committees;Gilead: Speakers Bureau. Lawson: Alexion: Honoraria. Kroeger: Neovii: Honoraria, Research Funding;Sanofi: Honoraria;Jazz: Honoraria, Research Funding;Celgene: Honoraria, Research Funding;Riemser: Honoraria, Research Funding;Gilead/Kite: Honoraria;AOP Pharma: Honoraria;Novartis: Honoraria. Styczynski: MSD, Pfizer, Giled, TEVA, Jazz, Novartis: Honoraria, Speakers Bureau. Ljungman: Takeda: Consultancy, Other: Endpoint committee, speaker;Enanta: Other: DSMB;Janssen: Other: Investigator;OctaPharma: Other: DSMB;Merck: Other: Investigator, speaker;AiCuris: Consultancy.

Sars-Cov-2 Infection Promotes Endothelial Dysfunction and Thrombosis in a Mouse Model of COVID-19

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most infected individuals are asymptomatic or show only mild symptoms, but 20% of infected individuals become severely ill resulting in a 2-5% mortality rate for severe infections. Men, the elderly and patients with comorbidities (such as cardiovascular disease, hypertension, diabetes, and obesity) are more likely to develop severe disease. Clinical features characterizing severe COVID-19 cases include inflammation and thrombosis, but the molecular mechanisms underlying these processes remain elusive. K18 hACE2 transgenic mice express the SARSCoV-2 receptor human angiotensin-converting enzyme 2 (hACE2) under the control of the human cytokeratin 18 (K18) promoter. K18 hACE2 mice express hACE2 in airway epithelial cells and are susceptible to SARS-CoV-1 and SARS-CoV-2 infections. At the dose of 10 5 PFU/mouse, all SARS-CoV-2-infected K18 hACE2 mice rapidly lose weight and succumb to viral infection by 5-6 days post infection. Morbidity and mortality correlated with SARS-CoV-2 replication in the nasal turbinates and lungs. Notably, susceptibility was highly associated with a local and systemic cytokine/chemokine storm. SARS-CoV-2 infection in K18 hACE2 mice recapitulates many of the pathological findings observed in human patients offering a reliable animal model for the study of SARS-CoV-2 pathogenesis. Infection with a lower viral dose (10 4 and 2.5x10 3 PFU/mouse) prolongs the symptomatic phase of the infection, postponing time of death up to 16 days post infection (mortality rate at 10 4 PFU: ~40% in females, 100% in males;mortality rate at 2.5x10 3 PFU: ~30% in females, ~55% in males). At these lower viral doses, K18 hACE2 mouse males exhibited both increased susceptibility to the SARS-CoV-2 infection and more severe disease. Male mice showed increased mortality associated with an increase in weight loss and decrease in body temperature. Disease characteristics showed striking similarities with reported human COVID-19 cases, including severely reduced O 2 saturation. The pathogenesis of severe COVID-19 cases involves both virus-induced cell damage and secondary tissue damage due to a vicious cycle of dysregulated - hyperactive coagulation and inflammatory pathways that present as “a cytokine storm”, endothelial dysfunction, and “immunothrombosis”. Analysis of murine plasma analytes from infected mice revealed additional pathogenetic features resembling SARS-CoV-2 infection in humans. High circulating D-dimer levels are now considered a main predictor of poor outcome of SARS-CoV-2 infection. Notably, we also observed a progressive increase of circulating D-dimer levels in the plasma of K18 hACE2 infected mice peaking at day 7 post infection, suggestive of a hypercoagulable state. Moreover, similar to humans, the increase in soluble thrombomodulin plasma concentration and its correlation with disease severity was indicative of endothelial activation and dysfunction in K18 hACE2 infected mice. SARS-CoV-2 infection-induced changes of coagulation and endothelial activation in mice resulted in a biphasic alteration of endothelial permeability where an initial increase in vascular permeability, peaking at day 5 post infection, was followed by a sudden decrease in Evan's blue dye extravasation in the lung parenchyma and characterized by the appearance of areas of hemorrhagic infarction indicative of thrombotic events. Altogether, our results identify the K18 hACE2 transgenic mouse as an important small animal model to study the molecular mechanisms involved in the derangement of the finely tuned interaction between the immune and coagulation systems associated with severe cases of SARS-CoV-2 infections. Disclosures: Mosnier: Hematherix: Membership on an entity's Board of Directors or advisory committees;Coagulant Therapeutics: Research Funding.

Nursing role in the covid-19 pandemic: Systematic review

The role of the nurse is based on providing comprehensive quality care to the healthy or sick person and accompanying him/her in the healing and rehabilitation process, and if nec-essary, at the time of death. Objective: To examine the role of nursing in the Covid-19 pandemic through a systematic review. Methodology: A systematic investigation was carried out in the scientific databases PubMed, SciElo, Google Scholar, Nursing Journal combining the Boolean operators AND and OR, in Spanish, English and Portuguese. Results: The literary search reported 1243 documents after the ap-plication of the selection criteria and evaluative reading, 32 articles were included for analysis due to their belonging and contribution to the fulfillment of the objective. Conclusions: It is possible to affirm that the pandemic caused by Covid-19 placed the health systems in different challenges, where the nurse played a transcendental and recognized role, standing out for being the heart and fundamental pillar in the different levels of care, demonstrating their safety and leadership by being in a frontline scenario. © 2021, Venezuelan Society of Pharmacology and Clinical and Therapeutic Pharmacology. All rights reserved.

Syncope: A worrisome presenting symptom during the first wave of COVID-19 in Italy

Background: COronaVIrus Disease 19 (COVID-19) pandemic is a global health emergency. Since the first reported cases in Asia, the virus has now spread worldwide. Given its high contagiousness, one of the greatest challenges is early detection of infected patients. People affected by COVID-19 have had a wide range of presenting symptoms, from very mild to severe, including fever, cough, shortness of breath, gastrointestinal upset, anosmia and ageusia among others. Syncope as the presenting symptom of COVID-19 has been reported in case series or small sample size retrospective studies with variable results in terms of incidence, characteristics and outcomes. Purpose: The aim of the present analysis is to investigate all consecutive patients with COVID-19 who presented with syncope during the first wave of the pandemic to a high-volume Emergency Department (ED) in Italy. Methods: A total of 569 patients diagnosed with COVID-19 by positive nose and throat swab and admitted to the hospital between February 20th, 2020 (day of first reported COVID-19 case in Italy) and April 23rd, 2020 were retrospectively evaluated. Results: Syncope has been reported as the initial symptom which prompted medical attention in 46 out of 569 patients (8%). Mean age of patients presenting with syncope was 72±15 years, 28 were males. Baseline patients' clinical characteristics are reported in Table 1. In 18 out of 46 patients (39%) syncope was an isolated finding, being fever and cough the two most commonly associated symptoms. Arrhythmic etiology was excluded since no arrhythmia was observed at device interrogation or with ECG/prolonged heart monitoring during hospitalization. No significant abnormalities were present at baseline ECG. At the time of admission, all patients were normotensive, median O2 saturation was 94.5%, median Ddimer 362 ng/ml. One-third of the patients presenting with syncope had a complicated clinical course with quite rapid deterioration requiring noninvasive ventilation (30%) and intensive care unit admission with intubation (11%). In our group of consecutive patients with COVID-19 who presented with syncope, the mortality rate was surprisingly high, 15/46 (32%), compared to the mortality rate of the COVID population admitted to our hospital with other symptoms 93/523 (18%), p=0.023. Six out of 15 patients died in the ED, mainly during their first day of hospitalization. The other 9 had a quite rapid deterioration in the following days and died within a week (median syncope-to-death time was 7 days). Conclusion: Despite our new finding needs confirmation in studies with larger sample size, our report shows how syncope may be the presenting symptom of COVID-19. Whether the exact mechanism has to be demonstrated, the mortality rate in patients presenting with syncope is higher than the mortality rate of patients presenting with other symptoms;therefore COVID-19 patients presenting with syncope should be on a watch list for rapid deterioration.