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AIM: To evaluate the predictive properties of several common prognostic scores regarding survival outcomes in hospitalized COVID-19 patients. METHOD(S): We retrospectively reviewed the medical records of 4014 consecutive COVID-19 patients hospitalized in our tertiary level institution from March 2020 to March 2021. Prognostic properties of the WHO COVID-19 severity classification, COVID-GRAM, Veterans Health Administration COVID-19 (VACO) Index, 4C Mortality Score, and CURB-65 score regarding 30-day mortality, in-hospital mortality, presence of severe or critical disease on admission, need for an intensive care unit treatment, and mechanical ventilation during hospitalization were evaluated. RESULT(S): All of the investigated prognostic scores significantly distinguished between groups of patients with different 30-day mortality. The CURB-65 and 4C Mortality Score had the best prognostic properties for prediction of 30-day mortality (area under the curve [AUC] 0.761 for both) and in-hospital mortality (AUC 0.757 and 0.762, respectively). The 4C Mortality Score and COVID-GRAM best predicted the presence of severe or critical disease (AUC 0.785 and 0.717, respectively). In the multivariate analysis evaluating 30-day mortality, all scores mutually independently provided additional prognostic information, except the VACO Index, whose prognostic properties were redundant. CONCLUSION(S): Complex prognostic scores based on many parameters and comorbid conditions did not have better prognostic properties regarding survival outcomes than a simple CURB-65 prognostic score. CURB-65 also provides the largest number of prognostic categories (five), allowing more precise risk stratification than other prognostic scores.
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Aim To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). Methods We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiarylevel hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. Results Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P = 0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P < 0.001) but not among patients who received it after starting HFOT (P = 0.499) or MV (P = 0.380). Conclusion Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.Copyright © 2022 Medicinska Naklada Zagreb. All rights reserved.
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Since COVID-19 pandemic has started, there have been reports that SARS-CoV-2 infection induces pro-thrombotic state. Even though the disease presents foremost with respiratory symptoms, high frequencies of both venous and arterial thromboses have been observed while suggesting different molecular mechanisms. University Hospital Dubrava has been Croatia capital's COVID-19 centre for almost a year and a half treating almost 10.000 patients until today. We retrospectively analysed venous and arterial thrombotic events among 4014 patients hospitalized due to COVID-19. Venous thromboembolic events (VTE) occurred in 5.3% and arterial thrombotic events (ATE) in 5.8% of patients. Majority of ATE occurred prior or on the day of admission while VTE were mainly detected during hospitalization (screening). Majority of both occurred prior to intensive care unit (ICU) admission, but both were associated with higher need for ICU care and prolonged immobilization. In multivariate logistic regression analysis independent factors associated with VTE were metastatic malignancy, known thrombophilia, higher D-dimers, longer duration of disease on admission, bilateral pneumonia, longer duration of hospitalization and immobilization for at least one day. On the other hand, factors that showed to be associated with ATE were less severe COVID-19, higher Charlson comorbidity index, history of arterial diseases, aspirin use, lower C reactive protein, better functional status on admission and immobilization for at least one day. In conclusion, venous and arterial thromboses differ in all above mentioned factors thus leaving room for appropriate prevention, intervention and treatment.
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Background: Follicular lymphoma (FL) is a systemic neoplasm of the lymphoid tissue arising from B cell proliferation. The novel monoclonal anti-CD20 antibody obinutuzumab in combination with chemotherapy has been widely accepted as the first choice in front line treatment of FL. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19) is causing increased mortality among patients with lymphoproliferative disorders compared with the general population. Furthermore, there are some concerns in terms of morbidity and mortality for patients with FL because of their immunocompromised status induced by recent exposure to cytotoxic chemotherapy, especially bendamustine and anti-CD20. Aims: To investigate efficacy and safety of immunochemotherapy protocols for patients with newly diagnosed FL during COVID-19 pandemic. Methods: We retrospectively investigated medical data of all patients with newly diagnosed FL grade 1, 2 or 3A from Croatian hematologic registry in period from April 2019 to March 2021. Only patients which required systemic treatment were included in the analysis. All patients received obinutuzumab (G) in combination with either CHOP, bendamustine (B) or CVP chemotherapy protocol. Treatment response was evaluated using international lymphoma response criteria. Results: We analyzed a total of 114 FL patients treated with G-chemotherapy. Mean age was 62.4 ±10.5 years. Majority of patients were female (71/114 (62.3%)). FL grade I was present in 45/114 (39.5%), grade II in 28/114 (24.6%), grade III in 27/114 (23.7%) and not specified (but not IIIB) in 14/114 (12.3%) patients. A total of 61/114 (53.5%) patients were treated with G-B, 49/114 (43%) with G-CHOP and 4/114 (3.5%) with G-CVP immunochemotherapy. Similar rates of adverse events were observed in patients treated with G-CHOP and G-B Median follow up was 17 months. Overall response rate was 94%, complete remission (CR) in 68% and partial remission (PR) in 25% of patients. Median overall survival (OS) and progression free survival (PFS) were not reached with 12-months rates of 94% and 92%, respectively. Patients treated with G-CHOP had statistically significantly superior OS and PFS compared to patients treated with G-B (P=0.002 and P=0.006, respectively, Fig. 1). More favorable survival course associated with G-CHOP in comparison to G-B persisted in multivariate analysis (P=0,026, HR=15,12) after adjustment for age, sex, FLIPI grade and SARS-CoV-2 infection. Total of 12 patients died during the follow up and COVID-19 was cause of death in 5 patients. During the follow-up SARS-CoV-2 infection was diagnosed in 20/114 (17,5%) patients with overall mortality rate of 25%. All of the 7 patients treated with GCHOP recovered from SARS-CoV-2 infection and mortality rate in infected group of patients treated with G-B was 33% (4/12 patients). Image: Summary/Conclusion: Increased COVID-19 mortality in patients with lymphoproliferative disorders was observed in this study. Our group of patients had reduced OS and PFS compared to the GALLIUM trial and SARS-CoV-2 infection was the most pronounced risk factor for death. Even though in some studies bendamustine has shown to be less toxic and more effective than CHOP in FL, there are some important pandemic aspects that must be considered. Bendamustine exposure seems to be associated with worse outcome in case of the infection with SARS-CoV-2. These intriguing differences could play important role in treatment approach in COVID-19 pandemic. Future studies investigating hematological malignancies in COVID-19 pandemic are warranted.
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It was recently observed that use of remdesivir in Coronavirus disease 2019 (COVID-19) might be associated with higher occurence of transitory bradycardia. However, the clinical significance of this phenomenon is unknown. We have retrospectively investigated a cohort of 473 COVID-19 patients hospitalized in our institution from 9/2020 to 4/2021 who received remdesivir for acute COVID-19 infection. Median age was 65 years IQR (56-72.3). A total of 312 (66%) patients were male, 53 (11.2%) had atrial fibrillation (AF) and 141 (29.8%) used beta blockers (BB), respectively. Median Charlson comorbidity index (CCI) was 3 IQR (2-4). At the time of hospital admission, a total of 382 (80.8%) patients presented with severe and 83 (17.5%) with critical COVID-19 symptoms. Median C-reactive protein and Interleukin-6 levels on admission were 110.7 mg/L and 44.2 pg/ml, respectively. Bradycardia (heart rate <60 beats per minute) was present in only 1.3% patients before remdesivir treatment. The rate of bradycardia steadily increased up to day 5 of remdesivir treatment on which 16.8% patients experienced bradycardia that subsequently diminished after remdesivir discontinuation. Occurrence of bradycardia on day 5 of remdesivir treatment was significantly associated with lower odds of high flow oxygen therapy use (OR 0.33 95% CI (0.16-0.7);P=0.004), intensive care treatment (OR 0.43 (0.2- 0.91);P=0.027) and death during hospitalization (OR 0.33 95% CI (0.14-0.79);P=0.014). In the multivariate logistic regression analysis, absence of remdesivir day 5 bradycardia occurrence (OR 0.39;P=0.043), more severe WHO COVID-19 severity on admission (OR 3.32;P<0.001), older age (OR 1.01;P=0.012) and higher Charlson comorbidity index (OR 1.16;P=0.047) were independently associated with death during hospitalization. Our data suggest that remdesivir associated bradycardia might reflect more favorable disease course and has a substantial potential for improving prognostication of COVID-19 patients. Thus, the most frequent cardiovascular “adverse drug reaction” to remdesivir seems to be the sign of good prognosis. Underlying mechanisms of these phenomena are unknown at the moment.
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Methods: We investigated clinical characteristics, the severity of COVID-19 infection on admission, and its clinical course in patients with CLL hospitalized in our institution due to acute COVID-19 infection in the period from March 2020 to March 2021. Our institution University Hospital Dubrava was completely repurposed for the treatment of COVID-19 patients during the pandemic and served as a tertiary referral center. Patients were compared to age-, sex-, and adjusted Charlson comorbidity index (without points for the hematologic malignancy) matched patients without malignant disease chosen from the Registry of hospitalized COVID-19 patients from the same institution. Numerical variables were presented as the median and interquartile range (IQR) and categorical as frequencies and percentages. The Mann Whitney U test, the Chi-squared test, and the log-rank test were used. p-values <0.05 were considered statistically significant. All analyses were performed using the MedCalc statistical software ver 20.008. Results: Among 4014 hospitalized COVID-19 patients and among them 154 patients with hematological malignancies, we identified a total of 37 patients with CLL that were hospitalized due to acute COVID-19 infection. The median age of CLL patients was 68 years IQR (61-80), median Charlson comorbidity index was 5 points IQR (3-6). There were 25 (67.6%) males. Majority of CLL patients [34 (91.9%)] presented with severe or critical COVID-19 symptom severity on admission. The median duration of hospitalization was 15 days IQR (10-21.5). The need for high flow oxygen therapy was present in 11 (29.7%), mechanical ventilation in 7 (18.9%), intensive care unit treatment in 9 (24.3%), and death occurred in 11 (29.7%) patients, respectively. In comparison to 37 age-, sex-, and comorbidities matched hospitalized COVID-19 patients without the malignant disease (Charlson comorbidity index 3 points), patients with CLL patients had a similar frequency of severe or critical COVID-19 symptom severity on admission, similar CRP, ferritin, and D-dimer levels on admission. Also, a similar need for high-flow oxygen therapy, mechanical ventilation, intensive care unit treatment, and death during hospitalization was present in CLL and control cohorts (p>0.05 for all analyses). However, CLL patients were more likely to require longer hospitalization (median 15 vs. 10 days;p=0.017) and to receive antibiotics (48.6 vs. 24.3%;p=0.031) than control patients. Among CLL patients, no differences in survival or intensity of respiratory support were present between patients with and without previous anti CD20 exposure (p>0.05 for all analyses) but the possible tendency for better survival in patients with previous anti CD20 exposure. However, patients previously exposed anti CD20 therapies required significantly longer hospitalization (median 22 vs. 13 days;p=0.039). Remdesivir and convalescent plasma exposure had no significant associations with survival. Observed results are in line with the prolonged course of COVID-19 infection B-CLL patients with similar outcomes at 30 and 120 days compared to a matched population.
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AIM: To investigate how age, sex, and comorbidities affect the survival of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 4014 consecutive adults hospitalized for COVID-19 in a tertiary-level institution from March 2020 to March 2021. RESULTS: The median age was 74 years. A total of 2256 (56.2%) patients were men. The median Charlson-comorbidity-index (CCI) was 4 points;3359 (82.7%) patients had severe or critical COVID-19. A significant interaction between age, sex, and survival (P<0.05) persisted after adjustment for CCI. In patients <57 years, male sex was related to a favorable (odds ration [OR] 0.50, 95% confidence interval [CI] 0.29-0.86), whereas in patients >=57 years it was related to an unfavorable prognosis (OR 1.19, 95% CI 1.04-1.37). Comorbidities associated with inferior survival independently of age, sex, and severe/critical COVID-19 on admission were chronic heart failure, atrial fibrillation, acute myocardial infarction, acute cerebrovascular insult, history of venous thromboembolism, chronic kidney disease, major bleeding, liver cirrhosis, mental retardation, dementia, active malignant disease, metastatic malignant disease, autoimmune/rheumatic disease, bilateral pneumonia, and other infections on admission. CONCLUSION: Among younger patients, female sex might lead to an adverse prognosis due to undisclosed reasons (differences in fat tissue distribution, hormonal status, and other mechanisms). Patient subgroups with specific comorbidities require additional considerations during hospital stay for COVID-19. Future studies focusing on sex differences and potential interactions are warranted.
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AIM: To investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission. RESULTS: The median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI;and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index). CONCLUSION: RDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.
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AIM: To evaluate the burden and predictors of thromboembolic complications in a large real-life cohort of hospitalized patients with established coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the records of 4014 consecutive adult patients admitted to a tertiary-level institution because of COVID-19 from March 2020 to March 2021 for the presence of venous and arterial thrombotic events. RESULTS: Venous-thromboembolic (VTE) events were present in 5.3% and arterial thrombotic events in 5.8% patients. The majority of arterial thromboses occurred before or on the day of admission, while the majority of VTE events occurred during hospitalization. The majority of both types of events occurred before intensive care unit (ICU) admission, although both types of events were associated with a higher need for ICU use and prolonged immobilization. In multivariate logistic regression, VTE events were independently associated with metastatic malignancy, known thrombophilia, lower mean corpuscular hemoglobin concentration, higher D-dimer, lower lactate dehydrogenase, longer duration of disease on admission, bilateral pneumonia, longer duration of hospitalization, and immobilization for at least one day. Arterial thromboses were independently associated with less severe COVID-19, higher Charlson comorbidity index, coronary artery disease, peripheral artery disease, history of cerebrovascular insult, aspirin use, lower C reactive protein, better functional status on admission, ICU use, immobilization for at least one day, absence of hyperlipoproteinemia, and absence of metastatic malignancy. CONCLUSION: Among hospitalized COVID-19 patients, venous and arterial thromboses differ in timing of presentation, association with COVID-19 severity, and other clinical characteristics.
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Background Patients with hematologic malignancy have a higher risk of death from COVID-19 compared to the general population. A blunted immune response from both the underlying disease and applied treatment may contribute to development of more severe forms of COVID-19, absence of seroconversion, prolonged viral shedding, and might also impair humoral vaccine response. Factors influencing efficacy of SARS-CoV-2 vaccines in this patient population are still insufficiently explored. Methods We prospectively enrolled 143 patients with malignant or non-malignant hematologic diseases from University Hospital Centre Zagreb vaccinated between January and June 2021 with either mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer-BioNTech), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines. A qualitative assay against SARS-CoV-2 nucleocapsid antigen was used to detect prior infection;these patients (n=23) were excluded from the final analysis. Humoral response following vaccination was monitored using serological immunoassay registered for quantitative measurement of serum anti-SARS-CoV-2 RDB-spike protein antibodies. Both electrochemiluminescent assays performed by Cobas e801 analyzer (Roche Diagnostics, Mannheim, Germany) detect total antibodies (including IgG). Response was recorded after the first and second doses. A positive response was defined as > 0.8 U/mL. Upper and lower limits of quantification were 0,4 U/mL and 250 U/mL respectively. We reviewed patient records for demographics, underlying hematological diseases, current treatment, the total number of lines of therapy received, IgG levels, application of anti-CD20 monoclonal antibodies (mAbs) and corticosteroids in the last 6 months before vaccination, and subsequent SARS-CoV-2 infection. Inter-group comparisons were performed with Mann-Whitney U, χ 2, or Fisher's exact test as appropriate. ROC curve analysis was used to find optimized cut-off values of numerical variables regarding response to the second dose. P values <0.05 were considered statistically significant. MedCalc statistical software v 20.008 was used for all analyses. Results We evaluated a total of 120 patients who received at least one dose. Patient characteristics are summarized in Table 1. The majority received the Pfizer-BioNTech vaccine (66.7%), followed by Oxford-AstraZeneca (24.2%) and Moderna (9.2%). Data on humoral response after the first dose was available in 66 patients, among whom 20 (33%) achieved response with median specific IgG levels 6.1 U/mL. Response after the second dose was available in 90 patients;58 (64.4%) achieved response with median specific IgG levels 250 U/mL. The second dose significantly improved response both in terms of achieved response (P=0.031) and specific IgG levels (P<0.001). There were no significant differences in response or specific IgG levels regarding the type of the vaccine (P>0.05). Lower response rates after the second dose were achieved in patients aged >67 years (P<0.001;response in 32.4% vs. 83.9%), with specific diagnosis (P=0.002, driven by response in patients with non-Hodgkin's lymphoma (NHL;response in 29.2% NHL vs. 77.3% non-NHL) and chronic myeloid leukemia (CML;100% response in CML vs. 61.4% non-CML)), those receiving active treatment (50% vs. 88%;P<0.001), no prior hematopoietic stem cell transplantation (HSCT;51% vs. 93%;P<0.001) and prior anti-CD20 mAbs therapy (4% vs. 85%;P<0.001). Corticosteroid therapy (>120 mg prednisone equivalent dose) did not influence the response significantly (response in 88.9% vs. 42.1%;P=0.056), and neither did steroid type. Four (3,3%) patients tested positive for SARS-CoV-2 after vaccination, 2 of which had no humoral response, and 2 had received only one dose. Three patients required in-hospital treatment and oxygen supplementation. Conclusions Patients with hematologic diseases have lower serological response rates to SARS-CoV-2 vaccines than those previously reported in clinical trials. Our results also suggest they benefit from receiving both doses with no significant difference between vaccine types. Those in active treatment, no prior HSCT, diagnosed with NHL, and receiving anti-CD20 mAb seem more likely to be seronegative after receiving both doses. However, the present study did not examine potential confounding effects between these factors and these findings should be elaborated further in larger patient cohorts. [Formula presented] Disclosures: Aurer: Novartis: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Swixx/BMS: Honoraria;sanofi genzyme: Consultancy, Honoraria;Teva/Pilva: Honoraria;Abbvie: Consultancy, Honoraria;Eusapharma: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;takeda: Consultancy, Honoraria. Durakovic: Takeda, Novartis, Genyzme: Honoraria.
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Introduction: Obesity is among the risk factors for more severe forms of COVID-19. Obese people have higher prevalence of fatty liver and liver fibrosis. Aims & Methods: We aimed to investigate prevalence and severity od liver steatosis and fibrosis as assessed by transient elastography and their correlation with (a) the clinical severity of COVID-19 and (b) with 30-days mortality among non-critically ill patients hospitalized with COVID-19. We included patients >18 years, capable of giving informed consent, without conditions affecting liver stiffness measurement (LSM) (ALT>5xULN, congestive liver disease, extrahepatic biliary obstruction, infiltrative liver neoplasms). Transient elastography was used to assess liver stiffness and controlled attenuation parameter (CAP) for grading liver steatosis. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) (Knight SR et al. BMJ2020). Results: A total of 218 patients were included (145/218 (66.5%) males, median age 65 years, IQR (56 - 71), median BMI 28.2 kg/m2, IQR (25.4 - 31.4). History of chronic liver disease was present in 10/218 (4.6%) patients. Median 4CMS was 7, IQR (5 - 9), and 25/218 (11.5%) patients required high flow oxygen therapy (HFOT). A total of 15 patients died during 30 days from admission (7.9% of 191 patients with 30 days follow-up). Median LSM was 5.2 kPa, IQR (4.1 - 6.5) with 41/218 (18.8%) of patients presenting with LSM of >7 kPa and 11/218 (5%) with LSM >10 kPa. LSM was higher in patients with history of chronic liver disease (median 8.1 kPa vs 5.1 kPa;P=0.004), higher bilirubin (Rho=0.18;P=0.016) and higher GGT (Rho=0.25;P=0.001). Median LSM IQR was 13%, IQR (9 - 20). LSM IQR was weakly associated with higher BMI (Rho=0.14;P=0.038). No significant associations of LSM or LSM IQR with other laboratory and clinical parameters were found. Median CAP was 274 dB/m, IQR (232 - 320.5). CAP was associated with higher BMI (Rho=0.43;P<0.001). There was no significant association of CAP with LSM in an overall cohort, but a subgroup of patients with chronic liver disease (N=10) showed strong negative correlation between CAP and LSM (Rho=-0.81;P=0.005). No significant associations of CAP with other laboratory and clinical parameters were found. LSM IQR was not correlated to LSM or CAP values. Neither LSM, LSM IQR nor CAP were associated with 4CMS (P>0.05), although there was a tendency for a higher CAP values in patients with higher 4CMS (P=0.071). Also neither LSM nor CAP had significant association with the need for HFOT and 30-day mortality (P>0.05). However, patients who died had significantly lower LSM IQR (median 8.5% vs 14%;P=0.006), and those with LSM IQR ≤5% had 13 times higher risk of death (OR=13.2;95% C.I. 3.5 - 50.1). LSM IQR ≤5% was more frequently observed among patients on HFOT as well (28.6% vs 10.3%;P=0.038). Through multivariate logistic regression model building process investigating associations of LSM, LSM IQR, CAP, age, sex, BMI, 4CMS and need for HFOT with 30 day mortality, LSM IQR ≤5% (adjusted OR=19.4;P<0.001), 4CMS (adjusted OR=1.3;P=0.050) and need for HFOT (adjusted OR=14.0;P<0.001) were recognized as mutually independent predictors of higher mortality. Conclusion: Whereas LSM and CAP as non-invasive surrogates of liver fibrosis and steatosis failed to show correlation with disease severity and outcomes of patients with COVID-19, LSM IQR<5% was highly associated with the risk of 30-day mortality, independently of composite mortality score and the level of non-invasive oxygen support.
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Background: Patients with severe symptoms of COVID-19 often require prolonged hospitalization with reduced mobility due to both imposed restrictions and objective decline in functional status. Aims: Prompted by literature reports of high asymptomatic VTE prevalence in COVID-19 patients and our own clinical experience, we aimed to assess a prevalence of DVT among prolonged hospitalized COVID-19 patients without deep venous thrombosis (DVT) clinical suspicion and to investigate its potential predictors. Methods: During January 2021 we have prospectively undertaken bilateral lower extremity deep veins duplex ultrasound evaluation in 102 consecutive COVID-19 patients without clinical suspicion of DVT that were prolonged hospitalized in our institution. Eligible patients were adult (≥18 years) ward patients that required hospitalization for ≥7 days. Patients who developed clinical suspicion of DVT, unable to cooperate with the ultrasound procedure or were not sufficiently stable to undergo the ultrasound procedure were considered ineligible for the study. All patients received at least prophylactic doses of low molecular weight heparin. Results: Median age was 71.5 years. A total of 54/102 (52.9%) patients were males, 96/102 (94.1%) required oxygen-supplementation therapy. Median length of hospitalization at the time of evaluation was 18 days and median time from the start of COVID-19 symptoms was 27 days. DVT was detected in 26/102 (25.5%) patients without clinical suspicion. Distal DVT was the most common [22 patients (84.6% of the DVT cohort;21.6% of the overall cohort)]. Proximal DVT was present in four patients (16% of the DVT cohort;3.9% of the overall cohort), among them three had popliteal thrombosis and one had femoral thrombosis. Pulmonary embolism (PE) was detected in 17/70 (24.3%) patients who were similarly distributed among patients with and without asymptomatic DVT [5/17 (29.4%) and 12/53 (22.6%);P=0.571]. Patients that were mechanically- ventilated ICU survivors presented with highest frequency of DVT [6/10 (60%)], whereas patients treated with high-flow oxygen therapy and prolonged-hospitalized patients had similar DVT frequency [7/33 (21.2%) and 13/59 (22%), respectively];P=0.031, Figure. D-dimers at the time of hospital admission showed no significant association with the presence of DVT (P=0.280) but there was a statistically significant trend of higher frequency of asymptomatic DVT among patients with higher level of control D-dimers (P=0.034). Patients with and without DVT significantly differed in modified IMPROVE (median 3 and 2 points, respectively;P=0.021) and IMPROVEDD VTE risk-scores (median 4 and 3 points, respectively;P=0.029). Only 17/26 (65.4%) of patients with DVT would fulfill post-discharge thromboprophylaxis criteria (modified-IMPROVE score ≥2 and D-dimers 2x above normal or modified IMPROVE score ≥4 (COVID-19 Treatment Guidelines Panel 2021)). Other variables that were significantly associated with the presence of DVT were known thrombophilia (P=0.015) and higher body temperature on admission (P=0.001). Intensity of thromboprophylaxis, previous anticoagulation, CRP, age, sex, COVID-19 clinical prognostic-scores (MEWS, 4C-mortality score) and Padua VTE risk-score were not significantly associated with the occurrence of DVT (P>0.05 for all analyses). Summary/Conclusion: Systematic ultrasound assessment of prolonged hospitalized severe COVID-19 patients prior to hospital discharge is probably needed, especially of ICU survivors, to timely recognize and appropriately treat patients with asymptomatic DVT.