Tomographic Findings in the Retina of Unvaccinated Patients with COVID Pneumonia: Prospective Longitudinal Study.

There is no definitive evidence on the extent of SARS-CoV-2's effect on the retina. This study aims to determine if the natural history of SARS-CoV-2 infection affects tomographic findings in the retina of patients with COVID-19 pneumonia. This is a prospective cohort study of patients hospitalized with COVID-19 pneumonia. The patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at a follow-up 12 weeks later. The primary outcomes were the central retinal thickness and central choroidal thickness, which were compared longitudinally and with non-COVID-19 historical controls. No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fiber layer (p = 0.21), or ganglion cell layer (p = 0.32). Patients with acute COVID-19 pneumonia showed significantly greater central retinal thickness than non-COVID controls (p = 0.006). In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID-19 infection and remain stable during 12 weeks. The central retinal thickness may increase in the acute phase of COVID-19 pneumonia, but more epidemiological studies using optical coherence tomography in the early stages of the disease are needed.

A Clinical Prediction Rule for Thrombosis in Critically Ill COVID-19 Patients: Step 1 Results of the Thromcco Study.

The incidence of thrombosis in COVID-19 patients is exceptionally high among intensive care unit (ICU)-admitted individuals. We aimed to develop a clinical prediction rule for thrombosis in hospitalized COVID-19 patients. Data were taken from the Thromcco study (TS) database, which contains information on consecutive adults (aged ≥ 18) admitted to eight Spanish ICUs between March 2020 and October 2021. Diverse logistic regression model analysis, including demographic data, pre-existing conditions, and blood tests collected during the first 24 h of hospitalization, was performed to build a model that predicted thrombosis. Once obtained, the numeric and categorical variables considered were converted to factor variables giving them a score. Out of 2055 patients included in the TS database, 299 subjects with a median age of 62.4 years (IQR 51.5-70) (79% men) were considered in the final model (SE = 83%, SP = 62%, accuracy = 77%). Seven variables with assigned scores were delineated as age 25-40 and ≥70 = 12, age 41-70 = 13, male = 1, D-dimer ≥ 500 ng/mL = 13, leukocytes ≥ 10 × 103/µL = 1, interleukin-6 ≥ 10 pg/mL = 1, and C-reactive protein (CRP) ≥ 50 mg/L = 1. Score values ≥28 had a sensitivity of 88% and specificity of 29% for thrombosis. This score could be helpful in recognizing patients at higher risk for thrombosis, but further research is needed.

COVID-19 and the beef market in Latin America: An impact assessment by supply and demand.

The impact of COVID-19 on agricultural markets, especially the beef market, represents one of the greatest food security challenges the world is facing in the post-pandemic era and, for this reason, has been widely documented. This study contributes to the literature through a comprehensive impact analysis of the effects of COVID-19 on both the demand and supply of beef in Latin America and thus provides valuable information for two of the most important links of the beef value chain. Robust econometric methods and a graphic analysis were used that give solidity to the investigation. The analysis used a data panel of supply and demand variables between 2018 and 2022 derived from the US Department of Agriculture. The results suggest that the beef market was strongly affected by the pandemic related health emergency, presenting decreases in both consumption and production. These effects are transitory, however, since the analysis of the post-pandemic data revealed that consumption and production return to normal and seem to grow until smoothing out over time.

COVID-19 and the beef market in Latin America: An impact assessment by supply and demand

The impact of COVID-19 on agricultural markets, especially the beef market, represents one of the greatest food security challenges the world is facing in the post-pandemic era and, for this reason, has been widely documented. This study contributes to the literature through a comprehensive impact analysis of the effects of COVID-19 on both the demand and supply of beef in Latin America and thus provides valuable information for two of the most important links of the beef value chain. Robust econometric methods and a graphic analysis were used that give solidity to the investigation. The analysis used a data panel of supply and demand variables between 2018 and 2022 derived from the US Department of Agriculture. The results suggest that the beef market was strongly affected by the pandemic related health emergency, presenting decreases in both consumption and production. These effects are transitory, however, since the analysis of the post-pandemic data revealed that consumption and production return to normal and seem to grow until smoothing out over time.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19–Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis

IMPORTANCE: Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19–induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN, SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a “control” non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19–related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19–associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27;95% CI, 0.82–1.98;p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS.

Thromboprophylaxis with standard-dose vs. flexible-dose heparin for hospitalized COVID-19 patients: a target trial emulation.

OBJECTIVES: To compare mortality of hospitalized COVID-19 patients under two low-molecular weight heparin (LMWH) thromboprophylaxis strategies: standard dose and variable dose (standard dose increased to intermediate dose in the presence of laboratory abnormalities indicating an increased thrombosis risk). STUDY DESIGN AND SETTING: Target trial emulation using observational data from 2,613 adults admitted with a COVID-19 diagnosis in Madrid, Spain between March 16 and April 15, 2020. RESULTS: A total of 1,284 patients were eligible. Among 503 patients without increased baseline thrombotic risk, 28-day mortality risk (95% confidence interval [CI]) was 9.0% (6.6, 11.7) under the standard dose strategy and 5.6% (3.3, 8.3) under the variable dose strategy; risk difference 3.4% (95% CI: -0.24, 6.9); mortality hazard ratio 1.61 (95% CI: 0.97, 2.89). Among 781 patients with increased baseline thrombotic risk, the 28-day mortality risk was 25.8% (22.7, 29.0) under the standard dose strategy and 18.1% (9.3, 28.9) under the intermediate dose strategy; risk difference 7.7% (95% CI: -3.5, 17.2); mortality hazard ratio 1.45 (95% CI: 0.81, 3.17). Major bleeding and LMWH-induced coagulopathy were rare under all strategies. CONCLUSION: Escalating anticoagulation intensity after signs of thrombosis risk may increase the survival of hospitalized COVID-19 patients. However, effect estimates were imprecise and additional studies are warranted.

A Cohort Study in Intensive Care Units: Health Decisions Related to Blood Transfusion during the COVID-19 Pandemic.

Critically ill polytrauma patients with hemorrhage require a rapid assessment to initiate hemostatic resuscitation in the shortest possible time with the activation of a massive transfusion or a critical hemorrhage management protocol. The hospital reality experienced during the COVID-19 pandemic in all countries was critical, as it was in Spain; according to the data published daily by the Ministry of Health on its website, during the period of this study, the occupancy rate of intensive care units (ICUs) by patients diagnosed with the novel coronavirus disease (COVID-19) rose to 23.09% in Spain, even reaching 45.23% at the end of January 2021. We aimed to analyze the changes observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic period regarding the effectiveness of Spanish ICUs in terms of mortality reduction. We present a cross-sectional study that compares two cohorts of patients admitted to ICUs across all autonomous communities of Spain with a diagnosis of polytrauma. Results: Only age was slightly higher at admission during the first wave of the pandemic (47.74 ± 18.65 vs. 41.42 ± 18.82 years, p = 0.014). The transfusion rate during the pandemic increased by 10.4% compared to the previous stage (p = 0.058). Regarding hemostatic components, the use of tranexamic acid increased from 1.8% to 10.7% and fibrinogen concentrates from 0.9% to 1.9%. In the case of prothrombin complex concentrates, although there was a slight increase in their use, there were no significant differences during the pandemic compared to the previous period. Conclusion: Mortality showed no difference before and during the pandemic, despite the observed change in the transfusion policy. In summary, the immediate and global implementation of patient blood management (PBM) based on clinical transfusion algorithms should be mandatory in all hospitals in our country.

Overview of coronavirus pandemic

During the last months of 2019, numerous cases of respiratory illness such as pneumonia and acute respiratory distress syndrome were described in Wuhan, the capital city of Hubei province in China. At the same time, several research groups identified and reported the etiological agent, that included within the Coronaviridae family and the order Nidovirales, named SARS-CoV-2. Subsequently, the pathological and clinical status caused by the pathogen is commonly known as Coronavirus disease 2019 (COVID-19). In a short period, the outbreak of emerging spread across the world. Therefore the World Health Organization declared a public health emergency of international concern on January 30, 2020, and as a pandemic on March 11, 2020. Many different public health and epidemiological studies have been published since the COVID-19 outbreak, but fatality rates (those that relate the number of cases to mortality) are difficult to assess with certainty. Mean and median case-fatality rates worldwide are near to 3% and 2%, respectively. The median infection fatality calculated from serologic prevalence varies from 0.00% to 1.63% but is mostly estimated between 0.27% and 0.9%. These indexes are influenced by geographic location, socioeconomic status, sex, age, and health conditions, among others.

Impact of the COVID-19 Pandemic on the Diagnosis and Prognosis of Melanoma.

BACKGROUND: Early detection of melanoma is one of the main diagnostic goals of dermatologists worldwide, due to the increasing incidence of the disease in our environment. However, the irruption of the SARS-CoV-2 pandemic has posed a challenge to global healthcare, forcing systems to focus their resources on the fight against COVID-19. METHODS: Retrospective cohort study. The exposed cohort were patients diagnosed with melanoma in the year after the general confinement in Spain (15 March 2020) and the unexposed cohort were patients with melanoma diagnosed in the previous year. RESULTS: 130 patients were included. No differences were observed between demographic characteristics in both cohorts. The mean Breslow of melanoma before the onset of the pandemic was 1.08, increasing to 2.65 in the year after the onset of the pandemic (p < 0.001). On the other hand, the percentage of melanomas in situ decreased from 38.96% to 16.98% in the year after the declaration of the state of alarm in Spain. CONCLUSIONS: The SARS-CoV-2 outbreak has led to a reduction in the early diagnosis of melanoma, with an increase in invasive melanomas with poor prognosis histological factors. This could lead to an increase in melanoma-related mortality in the coming years in our environment.

Thromboembolic Events in a Socio-Economically Disadvantaged Population with COVID-19 Admitted to a Medicalized Hotel in Madrid.

Background: The social determinants of health (SDOH) of patients with COVID-19-related thrombosis have been scarcely explored. Our objective was to investigate the cases of thrombosis in a group of socially disadvantaged populations with COVID-19. Methods: We investigated the thrombotic events that occurred in a cohort of migrant and Spanish patients with COVID-19 that were admitted to a medicalized hotel in Madrid. Demographic data, past medical history, and socio-economic backgrounds, such as monthly household income, level of education, and living conditions, were explored to determine the factors related to thrombosis. Results: A cohort of 383 subjects (mean age 55.4 ± 14.6 years old, 69% male), of which 58% were migrants, was studied. Fourteen (3.6%) cases of thrombosis were reported. Thrombosis was more frequent in Spanish than in migrant individuals (OR 5.3, 95%CI 1.4-19.5, p = 0.005). Neither a low monthly household income nor a low education level showed a statistical association with thrombosis (p ≥ 0.05). History of venous thromboembolism (OR 8.1, 95%CI 2.2-28.6) and being a current smoker (OR 4.7, 95%CI 1.3-16.0) were factors associated with thrombosis. Conclusions: The SDOH studied were not associated with thrombosis; however, further investigation must be performed to investigate the socio-economic conditions of subjects with COVID-19 with adverse outcomes such as thrombotic events.

Relationship between ABO Blood Group Distribution and COVID-19 Infection in Patients Admitted to the ICU: A Multicenter Observational Spanish Study.

Since the beginning of the COVID-19 pandemic in December 2019, a relationship between the ABO blood group type and the novel coronavirus SARS-CoV-2, the etiological agent of COVID-19, has been reported, noting that individuals with the O blood group are the least likely to be infected. Spain is one of the most badly affected countries worldwide, with high rates of patients diagnosed, hospitalized, and deceased due to COVID-19 infection. The present study aimed to analyze the possible relationship of ABO in COVID-19 patients hospitalized in different Spanish centers during the first wave of the COVID-19 pandemic, for which the ABO group was available. Physicians from the transfusion services of different Spanish hospitals, who have developed a multicenter retrospective observational study, were invited to participate voluntarily in the research and 12,115 patients with COVID-19 infection were admitted to the nine participating hospitals. The blood group was known in 1399 cases (11.5%), of which 365 (26.1%) were admitted to the ICU. Regarding the distribution of ABO blood groups, a significant increase in the non-O blood groups and reduction for the O blood group was observed in patients hospitalized due to COVID-19, compared to the reference general population. Among the patients admitted to the ICU, after multivariate analysis, adjusted for the rest of the confounding variables, patients with the O blood group presented a significantly lower risk for admission to the ICU. We conclude that an association was observed between patients with the O blood group and their lower susceptibility to SARS-CoV-2 infection, both for those admitted to the hospitalization ward and for those who required admission to the ICU.

Approximation to the Consumption of Healthcare Resources and the Economic Cost of SARS-CoV-2 Patient Management: A Retrospective Study.

Spain has become one of the countries most affected by coronavirus disease 2019 (COVID-19), with the highest testing rates, and one of the worst-performing countries in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. There are no studies related to the consumption of health resources and the economic cost of the SARS-CoV-2 virus. We present a retrospective analysis of 9,811 (Primary Care and Hospital) patients which aimed to estimate public health expenditure by the consumption of health resources due to COVID-19. According to the results, the gender distribution of patients has a similar rate in both groups, with slightly higher rates in women. Similarly, age is the same in both groups, with a median of 62 years in the case of hospitalizations and 61 years in the case of primary care; using a weighted average of these rates and costs, we can estimate that the average cost of care per patient infected with the SARS-CoV-2 virus, regardless of the course is €2373.24. We conclude that a patient with COVID-19 without hospitalization costs €729.79, while the expenses of a hospitalized patient are between €4294.36 and €14440.68, if there is ICU admission.

Role of medical comorbidity in the association between psychiatric disorders and mortality among patients with COVID-19.

We examined whether excess chronic medical comorbidity mediated excess COVID-19 inpatient mortality among people with mental disorders in the early phase of the pandemic, a question with important implications for public health and clinical decision-making. Using records of 2599 COVID-19 hospitalized patients, we conducted a formal causal mediation analysis to estimate the extent to which chronic comorbidity mediates the association between mental disorders and COVID-19 mortality. The Odds Ratio (95% CI) for Natural Indirect Effect and Controlled Direct Effect were 1.07(1.02, 1.14) and 1.40 (1.00, 1.95), respectively, suggesting that a large proportion of excess COVID-19 mortality among people with mental disorders may be explained by factors other than comorbidity.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).

The Impact of Hospital Capacity Strain: a Qualitative Analysis of Experience and Solutions at 13 Academic Medical Centers.

BACKGROUND: Hospital capacity strain impacts quality of care and hospital throughput and may also impact the well being of clinical staff and teams as well as their ability to do their job. Institutions have implemented a wide array of tactics to help manage hospital capacity strain with variable success. OBJECTIVE: Through qualitative interviews, our study explored interventions used to address hospital capacity strain and the perceived impact of these interventions, as well as how hospital capacity strain impacts patients, the workforce, and other institutional priorities. DESIGN, SETTING, AND PARTICIPANTS: Qualitative study utilizing semi-structured interviews at 13 large urban academic medical centers across the USA from June 21, 2019, to August 22, 2019 (pre-COVID-19). Interviews were recorded, professionally transcribed verbatim, coded, and then analyzed using a mixed inductive and deductive method at the semantic level. MAIN OUTCOME MEASURES: Themes and subthemes of semi-structured interviews were identified. RESULTS: Twenty-nine hospitalist leaders and hospital leaders were interviewed. Across the 13 sites, a multitude of provider, care team, and institutional tactics were implemented with perceived variable success. While there was some agreement between hospitalist leaders and hospital leaders, there was also some disagreement about the perceived successes of the various tactics deployed. We found three main themes: (1) hospital capacity strain is complex and difficult to predict, (2) the interventions that were perceived to have worked the best when facing strain were to ensure appropriate resources; however, less costly solutions were often deployed and this may lead to unanticipated negative consequences, and (3) hospital capacity strain and the tactics deployed may negatively impact the workforce and can lead to conflict. CONCLUSIONS: While institutions have employed many different tactics to manage hospital capacity strain and see this as a priority, tactics seen as having the highest yield are often not the first employed.

"Stay at Home": The Effects of the COVID-19 Lockdown on Household Food Waste in Colombia.

Household food waste represents one of the main challenges for sustainable development as this directly affects the economy of food consumers, the loss of natural resources and generates additional greenhouse gas emissions. The COVID-19 pandemic and its mitigation strategies caused one of the most serious economic crises in recent decades and could become the worst economic crisis that Latin America has had in its history. The objective of this study is to analyze changes in food waste behavior during the COVID-19 lockdown in Colombia in 2020, applying the Theory of Planned Behavior (TPB). For this purpose, we conducted a survey with 581 Colombian food consumers, which examined the influence of intentions to not waste food, subjective norms, some situational predictors, questions related to the COVID-19 pandemic, and the control of perceived behavior on food waste. The results suggest that the TPB can predict the intention to not waste food and, through it, the actual household food waste behavior, considering the lockdown in Colombia as an external shock. We observe that regarding the intention to not waste food, the most relevant variables are attitudes, subjective norms, control of the perceived behavior, and concerns regarding the Covid-19 pandemic. These variables increase the probability on average by a 0.8 Odds Ratio that the intention not to waste food increases, too. Regarding food waste behavior, whether it is considered ordinal or nominal, we see that the most relevant variables are intention, financial attitudes, and control of perceived behavior, doubling the probability that food waste behavior will improve. Based on the results, we provide recommendations for interested stakeholders that can help in the design of instruments for household food waste reduction.

Screening Protocol and Prevalence of Venous Thromboembolic Disease in Hospitalized Patients With COVID-19.

BACKGROUND: SARS-CoV-2 disease (COVID-19) induces endothelial damage and sustained hypoxia and facilitates immobilization as factors of hypercoagulability. OBJECTIVES: The objective of our study was to assess the prevalence of venous thromboembolic disease (VTD) in COVID-19 patients and the usefulness of VTD screening based on age-adjusted D-dimer and point-of-care ultrasound (POCUS). PATIENTS/METHODS: We conducted a single cohort, prospective observational study in 102 consecutive hospitalized patients. RESULTS: A total of 102 POCUS and 39 pulmonary computed tomography angiography (PCTA) were performed diagnosing 27 VTD (26.5%): 17 deep vein thrombosis (DVT) (16.6% positive POCUS) and 18 pulmonary embolism (PE) (46.2% positive PCTA). COVID-19 patients with VTD were older (P < .030), had higher D-dimer (P < .001), higher International Society on Thrombosis and Hemostasis score (P < .001), and higher mortality (P = .025). However, there were no differences in inflammatory laboratory parameters neither in the cytokine storm syndrome (CSS) development. The ROC curve for D-dimer showed an AUC of 0.91. We have evidenced that patients with D-dimer between 2000 and 6000 ng/mL could benefit from a screening strategy with POCUS given the high sensitivity and specificity of the test. Furthermore, patients with D-dimer ≥6000 ng/mL should undergo POCUS and PCTA to rule out DVT and PE, respectively. CONCLUSIONS: In our cohort, 26.5% of the patients presented VTD. Screening strategy based on age-adjusted D-dimer and POCUS proved high sensitivity and specificity. Future trials focused on screening strategies are necessary to early detect the presence of DVT and PE and determine thromboprophylaxis strategies in patients with COVID-19.

In Silico and In Vitro Analyses Validate Human MicroRNAs Targeting the SARS-CoV-2 3'-UTR.

COVID-19 pandemic is caused by betacoronavirus SARS-CoV-2. The genome of this virus is composed of a single strand of RNA with 5' and 3'-UTR flanking a region of protein-coding ORFs closely resembling cells' mRNAs. MicroRNAs are endogenous post-transcriptional regulators that target mRNA to modulate protein expression and mediate cellular functions, including antiviral defense. In the present study, we carried out a bioinformatics screening to search for endogenous human microRNAs targeting the 3'-UTR of SARS-CoV-2. Results from the computational techniques allowed us to identify 10 potential candidates. The capacity of 3 of them, together with hsa-miR-138-5p, to target the SARS-CoV-2 3'-UTR was validated in vitro by gene reporter assays. Available information indicates that two of these microRNAs, namely, hsa-miR-3941 and hsa-miR-138-5p, combine effective targeting of SARS-CoV-2 genome with complementary antiviral or protective effects in the host cells that make them potential candidates for therapeutic treatment of most, if not all, COVID-19 variants known to date. All information obtained while conducting the present analysis is available at Open Science Framework repository.

Bleeding risk in hospitalized patients with COVID-19 receiving intermediate- or therapeutic doses of thromboprophylaxis.

INTRODUCTION: Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID-19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. METHODS: We performed a cohort study of patients hospitalized for COVID-19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. RESULTS: During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate- and 618 (31%) therapeutic-dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non-major bleeding. The 30-day all-cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%-54%) and for non-major bleeding 32% (95% CI: 24%-40%). Multivariable analysis showed increased risk for in-hospital major bleeding associated with D-dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38-3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02-3.95), critical illness (HR, 1.91; 95% CI, 1.14-3.18), and therapeutic-intensity anticoagulation (HR, 1.43; 95% CI, 1.01-1.97). CONCLUSIONS: Among patients hospitalized with COVID-19 receiving intermediate- or therapeutic-intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic-intensity anticoagulation, critical illness, and elevated D-dimer or ferritin levels at admission were associated with increased risk for major bleeding.