Effectiveness and safety of extended thromboprophylaxis in post-discharge patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The effect of extended thromboprophylaxis in improving the prognosis of adult patients with coronavirus disease 2019 (COVID-19) after discharge remains debatable. This meta-analysis was aimed to determine the advantages and disadvantages of extended thromboprophylaxis in these patients. METHODS: Different databases such as PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies that evaluated the effects of extended thromboprophylaxis in post-discharge patients with COVID-19 until 13 June 2022. The primary efficacy outcome was defined by the composite outcome of thromboembolism and all-cause mortality, and the safety outcome was defined by bleeding events. The odds ratios (ORs) and 95 % confidence intervals (CIs) of efficacy and safety outcomes were calculated using fixed- or random-effects model. Interaction analysis was performed to assess and compare observational studies and randomised controlled trials (RCTs). A sensitivity analysis was performed after excluding studies of poor quality. RESULTS: Eight studies involving 10,148 patients were included. The results confirmed that extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, was significantly associated with reduced composite outcome in high-risk post-discharge patients with COVID-19 (OR: 0.52; 95 % CI: 0.41-0.67, P = 0.000). Interaction analysis revealed that the effect estimates were consistent between the RCT and observational studies (Pinteraction = 0.310). Furthermore, extended thromboprophylaxis did not increase the risk of major bleeding events (OR: 1.64; 95 % CI: 0.95-2.82, P = 0.075). CONCLUSION: In post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, can significantly reduce the risk of thrombosis and all-cause mortality without increasing the risk of major bleeding events. REGISTRATION: PROSPERO CRD42022339399.

Warfarin anticoagulation management during the COVID-19 pandemic: The role of internet clinic and machine learning

Background: Patients who received warfarin require constant monitoring by hospital staff. However, social distancing and stay-at-home orders, which were universally adopted strategies to avoid the spread of COVID-19, led to unprecedented challenges. This study aimed to optimize warfarin treatment during the COVID-19 pandemic by determining the role of the Internet clinic and developing a machine learning (ML) model to predict anticoagulation quality. Methods: This retrospective study enrolled patients who received warfarin treatment in the hospital anticoagulation clinic (HAC) and “Internet + Anticoagulation clinic” (IAC) of the Nanjing Drum Tower Hospital between January 2020 and September 2021. The primary outcome was the anticoagulation quality of patients, which was evaluated by both the time in therapeutic range (TTR) and international normalized ratio (INR) variability. Anticoagulation quality and incidence of adverse events were compared between HAC and IAC. Furthermore, five ML algorithms were used to develop the anticoagulation quality prediction model, and the SHAP method was introduced to rank the feature importance. Results: Totally, 241 patients were included, comprising 145 patients in the HAC group and 96 patients in the IAC group. In the HAC group and IAC group, 73.1 and 69.8% (p = 0.576) of patients achieved good anticoagulation quality, with the average TTR being 79.9 ± 20.0% and 80.6 ± 21.1%, respectively. There was no significant difference in the incidence of adverse events between the two groups. Evaluating the five ML models using the test set, the accuracy of the XGBoost model was 0.767, and the area under the receiver operating characteristic curve was 0.808, which showed the best performance. The results of the SHAP method revealed that age, education, hypertension, aspirin, and amiodarone were the top five important features associated with poor anticoagulation quality. Conclusion: The IAC contributed to a novel management method for patients who received warfarin during the COVID-19 pandemic, as effective as HAC and with a low risk of virus transmission. The XGBoost model could accurately select patients at a high risk of poor anticoagulation quality, who could benefit from active intervention.

The Use of Oral Anticoagulation Is Not Associated With a Reduced Risk of Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P interaction = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.

Chest CT Imaging Features of Typical Covert COVID-19 Cases.

Purpose: To analyze the chest CT imaging findings of patients with initial negative RT-PCR and to compare with the CT findings of the same sets of patients when the RT-PCR turned positive for SARS-CoV-2 a few days later. Materials and methods: A total of 32 patients (8 males and 24 females; 52.9±7years old) with COVID-19 from 27 January and 26 February 2020 were enrolled in this retrospective study. Clinical and radiological characteristics were analyzed. Results: The median period (25%, 75%) between initial symptoms and the first chest CT, the initial negative RT-PCR, the second CT and the positive RT-PCR were 7(4.25,11.75), 7(5,10.75), 15(11,23) and 14(10,22) days, respectively. Ground glass opacities was the most frequent CT findings at both the first and second CTs. Consolidation was more frequently observed on lower lobes, and more frequently detected during the second CT (64.0%) with positive RT-PCR than the first CT with initial negative RT-PCR (53.1%). The median of total lung severity score and the number of lobes affected had significant difference between twice chest CT (P=0.007 and P=0.011, respectively). Conclusion: In the first week of disease course, CT was sensitive to the COVID-19 with initial negative RT-PCR. Throat swab test turned positive while chest CT mostly demonstrated progression.

Temporal changes of CT findings between non-severe and severe cases of COVID-19 pneumonia: a multi-center, retrospective, longitudinal Study.

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.

Patients With Lung Cancer Have High Susceptibility of COVID-19: A Retrospective Study in Wuhan, China.

Patients with lung cancer are presumed to be at high risk from COVID-19 infection due to underlying malignancy. A total of 31 COVID-19 patients with pre-diagnosed lung cancer and 186 age and sex matched COVID-19 patients without cancer in 6 hospitals in Wuhan, China were identified in our study. There was a significantly higher level of IL-6 in lung cancer group showed by multifactorial analysis. The restricted mean survival time in 10, 20, and 53 days in COVID-19 patients with lung cancer were ealier than non-cancer COVID-19 patients in the same observation time (all P values < 0.05). Our results indicated that pre-diagnosed lung cancer was associated with higher morbidity and mortality in COVID-19 patients.

Novel Coronavirus Disease 2019 (COVID-19) Pneumonia Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section Computed Tomography Features During Recovery.

BACKGROUND: Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. RESULTS: There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). CONCLUSIONS: The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week.

Fangcang Shelter Hospital in Wuhan: A radiographic report on a cohort of 98 COVID-19 patients.

Objectives: To present the temporal changes of CT manifestations in COVID-19 patients from a single fangcang shelter hospital and to facilitate the understanding of the disease course. Materials and Methods: This retrospective study included 98 patients (males: females, 43:55, mean year, 49±12 years) with confirmed COVID-19 at Jianghan fangcang shelter hospital admitted between Feb 05, 2020, and Feb 09, 2020, who had initial chest CTs at our hospital. Radiographic features and CT scores were analyzed. Results: A total of 267 CT scans of 98 patients were evaluated. Our study showed a high median total CT score of 7 within the first week from symptom onset, peaked in the 2nd week at 10, followed by persistently high levels of CT score with 9.5, 7 and 7 for the week 3, 4, and >4, respectively, and a prolonged median disease course (30 days, the median interval between the onset of initial symptoms and discharge). Ground-glass opacity (GGO) (58%, 41/71) was the earliest and most frequent finding in week 1. Consolidation (26%, 14/53) and mixed pattern (40%, 21/53) were predominant patterns in 2nd week. GGO and reticular were the main patterns of later phase CT scans in patients with relatively advanced diseases who had longer illness duration (≥4 weeks). Among the 94 CT abnormalities obtained within 3 days from the twice RT-PCR test turned negative, the mixed pattern was mainly presented in patients with disease duration of 2-3 weeks, for GGO and reticular were common during the whole course. Conclusion: Discharged patients from fangcang shelter hospital demonstrated a high extent of lung abnormalities on CT within the first week from symptom onset, peaked at 2nd week, followed by persistence of high levels and a prolonged median disease course. GGO was the predominant pattern in week 1, consolidation and mixed pattern in 2nd week, whereas GGO and reticular patterns in later stages (≥4 weeks).

Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid-19.

BACKGROUND: The management of critically ill patients with coronavirus disease 2019 (COVID-19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID-19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID-19 receiving CP treatments by total immunoglobulin G (IgG) titer collection. METHODS: Three patients with COVID-19 in this study were laboratory confirmed to be positive for SARS-CoV-2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200-225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed. RESULTS: No therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion. CONCLUSIONS: We recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID-19 pneumonia.