ABSTRACT
Background: The coronavirus disease-19 (COVID-19) and its variants have increased rapidly worldwide since December 2019, with respiratory disease being a prominent complication. As such, optimizing evaluation methods and identifying factors predictive of disease progress remain critical. The purpose of the study was to assess late phase (≥3 weeks) pulmonary changes using intensity-based computed tomography (CT) scoring in COVID-19 patients and determine the clinical characteristics predicting lung abnormalities and recovery. Methods: : We conducted a retrospective study on 42 patients (14 males, 28 females; age 65±10 years) with COVID-19. Only patients with at least 3 CT scans taken at least 3 weeks after initial symptom onset were included in the study. Two scoring methods were assessed: (1) area-based scoring (ABS) and (2) intensity-weighted scoring (IWS). Temporal changes in the average lung lesion were evaluated by the calculating the averaged area under the curve (AUC) of the CT score-time curve. Correlations between averaged AUCs and clinical characteristics were determined. Results: Using the ABS system, temporal changes in lung abnormalities during recovery were highly variable (P=0.934). By contrast, the IWS system detected more subtle changes in lung abnormalities during in COVID-19 patients, with consistent week-to-week relative reductions in IWS (P=0.025). Strong relationships were observed with D-dimer and C-reactive protein (CRP) levels on admission, with hazard ratios (HR)(95%CI) of 5.32 (1.25-22.6)(P=0.026) and 1.05 (1.10-1.09)(P=0.017), respectively. Conclusion: Our results suggest COVID-19-mediated pulmonary abnormalities persist well-beyond 3-weeks of symptom onset, with intensity-weighted rather than area-based scoring being more sensitive. Moreover, D-dimer and CRP levels were predictive of the recovery from the disease.
Subject(s)
COVID-19 , Respiratory Tract Infections , Lung DiseasesABSTRACT
SARS-CoV-2 variants brought new waves of infection worldwide. In particular, Delta variant (B.1.617.2 lineage) has become predominant in many countries. These variants raised the concern for their potential immune escape to the currently approved vaccines. ZF2001 is a subunit vaccine received emergency use authorization (EUA) in both China and Uzbekistan, with more than 100-million doses administrated with a three-dose regimen. The tandem-repeat dimer of SARS-CoV-2 spike protein receptor binding domain (RBD) was used as the antigen. In this work, we evaluated the neutralization of ZF2001-elicited antisera to SARS-CoV-2 variants including all four variants of concern (Alpha, Beta, Gamma and Delta) and other three variants of interest (Epsilon, Eta and Kappa) by pseudovirus-based assay. We found antisera preserved majority of the neutralizing activity against these variants. E484K/Q substitution is the key mutation to reduce the RBD-elicited sera neutralization. Moreover, ZF2001-elicited sera with a prolonged intervals between the second and third dose enhanced the neutralizing titers and resilience to SARS-CoV-2 variants.
ABSTRACT
BACKGROUND We recently described mortality of cardiac injury in COVID-19 patients. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiacinjury and mortality patterns in COVID-19 is unknown. METHODS This retrospective cohort study included 170 COVID-19 patients with cardiac injury at admission to Tongji Hospital in Wuhan from January 29–March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death were elevate levels of interleukin 6 (IL-6) (p<0.0001), Tumor Necrosis Factor-a (TNF-a) (p=0.0025), and C-reactive protein (CRP) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic pathway activation. Increasing cTnI levels were associated with those of increasing IL-6 (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS In COVID-19 patients with cardiac injury, admission IL-6 and D-dimer predicted subsequent elevation of cTnI and early death, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury. Condensed Abstract COVID-19 with cardiac injury is associated with worse survival. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiac injury and mortality patterns in COVID-19 is unknown. This study proved that cardiac injury in these patients is closely related to the activation of immunological and thrombotic pathways and can be predicted by admission biomarkers of these pathways. This study supports the strategy of biomarker-guided, point-of-care therapy that warrants further studies in a randomized manner to develop anti-immune and anti-thrombotic treatment regimens in severe COVID-19 patients with cardiac injury.
Subject(s)
Fractures, Stress , COVID-19 , Heart DiseasesABSTRACT
Objectives: To assess the late phase CT changes of COVID-19 patients, and figure out factors predicting lung abnormality in late phase.Methods: We conducted a retrospective study on 42 patients (14 males, 28 females; age 65±10 years) with COVID-19 admitted between February 7, 2020 and March 27, 2020. Only patients with at least 3 CT scans taken at least 3 weeks after initial symptom onset were included in the study. CT images were analyzed by 2 independent radiologists using different scoring: (1) area-based scoring (ABS); and (2) intensity-weighted scoring (IWS). Temporal changes in the average lung lesion were evaluated by averaged area under the curve (AUC) of the CT score-time curve. Correlations between averaged AUCs and clinical characteristics were determined. Results: Temporal changes in lung abnormalities during recovery (weeks 3 through 8) of CT findings using the ABS system were variable (P=0.934). By contrast, the IWS system detected more subtle changes in lung abnormalities during the late phase of recovery in COVID-19 patients, with consistent week-to-week relative reductions in IWS (P=0.025). In assessing the correlation between averaged AUCs and clinical characteristics, strong relationships were observed with D-dimer and C-reactive protein (CRP) levels on admission, with hazard ratios (HR)(95%CI) of 5.32 (1.25-22.6)(P=0.026) and 1.05 (1.10-1.09)(P=0.017), respectively. Conclusion: Our results suggest an intensity-weighted rather than area-based scoring system is more sensitive to detect subtle temporal CT changes in COVID-19, with D-dimer and CRP levels on admission being predictive of the time course of late phase recovery from the disease.
Subject(s)
COVID-19 , Lung Diseases , Skull Base NeoplasmsABSTRACT
Background In the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs. Methods Thirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening). Results Although AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9. Conclusions According to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.
Subject(s)
Coronavirus Infections , Encephalitis, Arbovirus , Heart DiseasesABSTRACT
We present a large, challenging dataset, COUGH, for COVID-19 FAQ retrieval. Similar to a standard FAQ dataset, COUGH consists of three parts: FAQ Bank, Query Bank and Relevance Set. The FAQ Bank contains ~16K FAQ items scraped from 55 credible websites (e.g., CDC and WHO). For evaluation, we introduce Query Bank and Relevance Set, where the former contains 1,236 human-paraphrased queries while the latter contains ~32 human-annotated FAQ items for each query. We analyze COUGH by testing different FAQ retrieval models built on top of BM25 and BERT, among which the best model achieves 48.8 under P@5, indicating a great challenge presented by COUGH and encouraging future research for further improvement. Our COUGH dataset is available at https://github.com/sunlab-osu/covid-faq.