The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Factors influencing diagnostic accuracy among intensive care unit clinicians - an observational study.

OBJECTIVES: Diagnostic errors are a source of morbidity and mortality in intensive care unit (ICU) patients. However, contextual factors influencing clinicians' diagnostic performance have not been studied in authentic ICU settings. We sought to determine the accuracy of ICU clinicians' diagnostic impressions and to characterize how various contextual factors, including self-reported stress levels and perceptions about the patient's prognosis and complexity, impact diagnostic accuracy. We also explored diagnostic calibration, i.e. the balance of accuracy and confidence, among ICU clinicians. METHODS: We conducted an observational cohort study in an academic medical ICU. Between June and August 2019, we interviewed ICU clinicians during routine care about their patients' diagnoses, their confidence, and other contextual factors. Subsequently, using adjudicated final diagnoses as the reference standard, two investigators independently rated clinicians' diagnostic accuracy and on each patient on a given day ("patient-day") using 5-point Likert scales. We conducted analyses using both restrictive and conservative definitions of clinicians' accuracy based on the two reviewers' ratings of accuracy. RESULTS: We reviewed clinicians' responses for 464 unique patient-days, which included 255 total patients. Attending physicians had the greatest diagnostic accuracy (77-90 %, rated as three or higher on 5-point Likert scale) followed by the team's primary fellow (73-88 %). Attending physician and fellows were also least affected by contextual factors. Diagnostic calibration was greatest among ICU fellows. CONCLUSIONS: Additional studies are needed to better understand how contextual factors influence different clinicians' diagnostic reasoning in the ICU.

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP).

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

Cystic fibrosis-related mortality in the United States from 1999 to 2020: an observational analysis of time trends and disparities.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.

Effect of Implementing a Commercial Electronic Early Warning System on Outcomes of Hospitalized Patients.

Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient's risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs.

Diagnostic Yield of Combined Lumbar Puncture and Brain MRI in Critically Ill Patients With Unexplained Acute Encephalopathy: A Retrospective Cohort Study.

Critically ill patients frequently experience acute encephalopathy, often colloquially termed "altered mental status" (AMS); however, there are no consensus guidelines or criteria about performing lumbar puncture (LP) and advanced neuroimaging in medical ICU patients with unexplained encephalopathy. OBJECTIVES: We sought to characterize the yield of combined LP and brain MRI (bMRI) in such patients as determined by both the frequency of abnormal results and the therapeutic efficacy of these investigations, that is, how often results changed management. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of medical ICU patients admitted to a tertiary academic center between 2012 and 2018 who had documented diagnoses of "AMS" and/or synonymous terms, no clear etiology of encephalopathy, and had undergone both LP and bMRI. MAIN OUTCOMES AND MEASURES: The primary outcome was the frequency of abnormal diagnostic testing results determined objectively for LP using cerebrospinal fluid (CSF) findings and subjectively for bMRI through team agreement on imaging findings deemed significant through retrospective chart review. We subjectively determined the frequency of therapeutic efficacy. Finally, we analyzed the effect of other clinical variables on the likelihood of discovering abnormal CSF and bMRI findings through chi-square tests and multivariate logistic regression. RESULTS: One hundred four patients met inclusion criteria. Fifty patients (48.1%) had an abnormal CSF profile or definitive microbiological or cytological data by LP, 44 patients (42.3%) had bMRI with significant abnormal findings, and 74 patients (71.2%) had abnormal results on at least one of these investigations. Few clinical variables were associated with the abnormal findings in either investigation. We judged 24.0% (25/104) of bMRI and 26.0% (27/104) of LPs to have therapeutic efficacy with moderate interobserver reliability. CONCLUSIONS: Determining when to perform combined LP and bMRI in ICU patients with unexplained acute encephalopathy must rely on clinical judgment. These investigations have a reasonable yield in this selected population.

In mechanically ventilated patients at nutritional risk, high protein did not reduce time to discharge alive.

SOURCE CITATION: Heyland DK, Patel J, Compher C, et al; EFFORT Protein Trial team. The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial. Lancet. 2023;401:568-576. 36708732.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS.

(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.

Patent Foramen Ovale and Ascending Aortic Dilatation Causing Platypnea-Orthodeoxia Syndrome.

Platypnea-orthodeoxia syndrome (POS) is an underdiagnosed clinical syndrome characterized by dyspnea (platypnea) and hypoxemia (orthodeoxia) in the upright position that resolves when recumbent. POS is often due to an underlying right-to-left shunt. Four broad mechanisms for the shunt have been described: intracardiac shunts, intrapulmonary shunts, hepatopulmonary syndrome, and pulmonary ventilation-perfusion mismatch. A 68-year-old male with a past medical history of chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, ascending aortic dilation (3.9 cm), myelofibrosis, and status post stem cell transplant complicated by graft versus host disease was found hypoxemic (oxygen saturation: 82%) on routine visit prompting hospitalization. Hypoxemia initially responded to 40% FiO2 but subsequently progressed to refractory hypoxemia on 100% FiO2. A chest computed tomography (CT) scan showed evidence of multiple segmental pulmonary emboli with patent central pulmonary arteries. Hypoxemia out of proportion to pulmonary embolism clot burden and examination findings consistent with orthodeoxia prompted further investigations. Nuclear medicine scan showed radiotracer activity in both brain and kidneys consistent with a small right-to-left shunt (5.9%). Transesophageal echocardiography (TEE) revealed a patent foramen ovale (PFO) with a right-to-left shunt across the atrial septum, with a maximum opening of 3.5 mm and tunnel length of 25 mm. Right heart catheterization (RHC) is consistent with the right-to-left shunt and normal right heart pressures. The degree of the shunt was not significant enough to explain the degree of hypoxemia, but all the diagnostic studies were performed in a supine position, possibly underestimating the degree of the shunt. PFO closure with transcatheter 30-mm Gore device (GORE® CARDIOFORM, Arizona, USA) decreased supplemental oxygen requirement from 75% high-flow nasal cannula (NC) to room air (RA) immediately after the procedure. The patient was subsequently discharged home on a baseline oxygen requirement of 2 L NC at nighttime. POS should be suspected when a patient develops severe hypoxemia after changing from a recumbent position to a sitting or standing position. The identification and correction of the shunting or mismatch often allow complete resolution of POS. Transthoracic echocardiography with agitated saline, TEE, and RHC are the diagnosis modalities of choice. Left heart cardiac catheterization remains the gold standard, which would demonstrate a mismatch in oxygen saturation between the pulmonary vein and the aorta. Our patient's PFO was successfully closed by a percutaneous transcatheter closure device leading to the complete resolution of hypoxemia immediately.

Do high-dose corticosteroids improve outcomes in hospitalized COVID-19 patients?

Coronavirus disease 2019 (COVID-19) is characterized by dysregulated hyperimmune response and steroids have been shown to decrease mortality. However, whether higher dosing of steroids results in better outcomes has been debated. This was a retrospective observation of COVID-19 admissions between March 1, 2020, and March 10, 2021. Adult patients (≥18 years) who received more than 10 mg daily methylprednisolone equivalent dosing (MED) within the first 14 days were included. We excluded patients who were discharged or died within 7 days of admission. We compared the standard dose of steroids (<40 mg MED) versus the high dose of steroids (>40 mg MED). Inverse probability weighted regression adjustment (IPWRA) was used to examine whether higher dose steroids resulted in improved outcomes. The outcomes studied were in-hospital mortality, rate of acute kidney injury (AKI) requiring hemodialysis, invasive mechanical ventilation (IMV), hospital-associated infections (HAI), and readmissions. Of the 1379 patients meeting study criteria, 506 received less than 40 mg of MED (median dose 30 mg MED) and 873 received more than or equal to 40 mg of MED (median dose 78 mg MED). Unadjusted in-hospital mortality was higher in patients who received high-dose corticosteroids (40.7% vs. 18.6%, p < 0.001). On IPWRA, the use of high-dose corticosteroids was associated with higher odds of death (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.45-3.14, p < 0.001) but not with the development of HAI, readmissions, or requirement of IMV. High-dose corticosteroids were associated with lower rates of AKI requiring hemodialysis (OR 0.33; 95% CI 0.18-0.63). In COVID-19, corticosteroids more than or equal to 40 mg MED were associated with higher in-hospital mortality.

Outcomes of Covid 19 patients-Are Hispanics at greater risk?

Disparities in outcomes exist in outcomes of coronavirus disease-19 (COVID-19). Little is known about other ethnic minorities in United States. We included all COVID-19 positive adult patients (≥18 years) hospitalized between March 1, 2020 and February 5th 2021. We compared in hospital mortality, use of intensive care unit services and inflammatory markers between non-Hispanic whites with non-White/Black Hispanic. Multivariable Cox proportional Hazard models were used to adjust for differences between the two groups. There were 4059 hospital admissions with COVID-19 in the study period. Of the 3288 White, 789 (24%) required intensive care unit (ICU) admission in comparison to 187 (24.3%) of the 770 Hispanics. Unadjusted mortality was higher in Whites than Hispanics (17.1% vs. 10.7%; p < 0.001). After adjusting for confounding variables, in-hospital mortality was not statistically different for Whites in comparison to Hispanics (hazard ratio [HR]: 0.96, 95% confidence interval [CI]: 0.76-1.21, p = 0.73). The adjusted rates of ICU transfers were significantly higher in Hispanics (HR: 1.34, 95% CI: 1.11-1.61, p = 0.002). Hispanics had significantly higher C-reactive protein, lactate dehydrogenase, and fibrinogen when compared to Whites. Hispanics as compared to Whites with COVID-19 require higher rates of ICU admission but have a similar mortality. Hispanics as compared to Whites with COVID-19 require higher rates of ICU admission but have a similar mortality.

Enhancing Analytical Reasoning in the Intensive Care Unit.

Clinical reasoning is prone to errors in judgment. Error is comprised of 2 components-bias and noise; each has an equally important role in the promulgation of error. Biases or systematic errors in reasoning are the product of misconceptions of probability and statistics. Biases arise because clinicians frequently rely on mental shortcuts or heuristics to make judgments. The most frequently used heuristics are representativeness, availability, and anchoring/adjustment which lead to the common biases of base rate neglect, misconceptions of regression, insensitivities to sample size, and fallacies of conjunctive, and disjunctive events. Bayesian reasoning is the framework within which posterior probabilities of events is identified. Familiarity with these mathematical concepts will likely enhance clinical reasoning. Noise is defined as inter or intraobserver variability in judgment that should be identical. Guidelines in medicine are a technique to reduce noise.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration: ClinicalTrials.gov Identifier: NCT04364737.

Incidence of Venous Thromboembolism and Effect of Anticoagulant Dosing in Hospitalized COVID-19 Patients.

Background: Coronavirus disease 2019 (COVID-19) is characterized by coagulopathy and thrombotic events. We examined factors associated with development of venous thromboembolism (VTE) in COVID-19 and to discern if higher dose of anticoagulation was beneficial in these patients. Methods: This study involves an observational study of prospectively collected data in the setting of a large community hospital in a rural setting in Northeast Georgia with COVID-19 between March 1, 2020 and February 5, 2021. Anticoagulation dose (none, standard, intermediate, and therapeutic dosages) was studied in adult patients (≥ 18 years). We constructed multivariable logistic regression model to examine the association of clinical characteristics with VTE. To examine the effect of dose of anticoagulation in preventing VTE, we used inverse probability weighted regression adjustment. Results: Of the 4,645 patients with COVID-19, 251 (5.4%) patients were found to have VTE. Of these, 91 had pulmonary embolism, 148 had deep venous thrombosis (DVT) and 12 had both. A total of 129 of VTE cases were diagnosed at admission. Of all admissions, 12.9% did not receive any DVT prophylaxis, 70.4% received prophylactic dose, 1.3% received intermediate dose and 15.5% received therapeutic dose. Male gender (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.0 - 2.4, P = 0.04) and Black race (OR: 2.0, 95% CI: 1.2 - 3.4, P = 0.01), along with higher levels of lactate dehydrogenase (LDH) and D-dimer were associated with higher odds of developing VTE. Patients receiving steroids had lower rates of VTE (3.9% vs. 8.3%, P < 0.001). Use of intermediate or therapeutic anticoagulation was not associated with lower odds of developing VTE. However, patients on therapeutic anticoagulation had lower odds of in hospital mortality when compared to standard dose (OR: 0.47, 95% CI: 0.27 - 0.80, P = 0.006). Conclusions: In COVID-19, D-dimer and LDH can be useful in predicting VTE. Steroids appear to have some protective role in development of VTE. Therapeutic anticoagulation did not result in lower rates of VTE but was associated with in-hospital mortality.