SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites.

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and aligned with reported neutralizing antibody binding sites. Similar LPE overlap occurred after infection and vaccination, with LPE clusters specific to each stimulus, where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function. Vaccine-specific LPEs tended to map to sites known or likely to be affected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein. Mapping LPEs to regions of known functional importance in this manner may accelerate vaccine evaluation and discovery of targets for site-specific therapeutic interventions.

An observational, retrospective, comprehensive pharmacovigilance analysis of hydroxychloroquine-associated cardiovascular adverse events in patients with and without COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Hydroxychloroquine (HCQ)-associated cardiovascular adverse events (CVAEs) have been increasingly reported. AIM: This study aimed to present an observational, retrospective, and comprehensive pharmacovigilance analysis of CVAE associated with HCQ in patients with and without COVID-19 using the US Food and Drug Administration Adverse Events Reporting System (FAERS) data from January 2020 to December 2020. METHOD: We identified 3302 adverse event reports from the FAERS database in the year 2020 and divided them into COVID-19 and non-COVID-19 groups, respectively. Then we analyzed whether there were differences in CVAEs between the two groups. RESULTS: We found that CVAE was higher in cases with COVID-19 compared to those without COVID-19, odds ratio (OR) of 1.26 and a 95% confidence interval (95% CI) of 1.02-1.54. Cases with COVID-19 treated with HCQ exhibited relatively higher proportions of torsade de points (TdP) and QT prolongation (OR 3.10, 95% CI 2.24-4.30), shock-associated TdP (OR 2.93, 95% CI 2.13-4.04), cardiac arrhythmias (OR 2.07, 95% CI 1.60-2.69), cardiac arrhythmia terms (including bradyarrhythmias and tachyarrhythmias) (OR 2.15, 95% CI 1.65-2.80), bradyarrhythmias (including conduction defects and disorders of sinus node function) (OR 2.56, 95% CI 1.86-3.54), and conduction defects (OR 2.56, 95% CI 1.86-3.54). CONCLUSION: Our retrospective observational analysis suggested that the proportion of CVAE associated with HCQ, especially TdP and QT prolongation, was higher in patients with COVID-19. Understanding the effects of COVID-19 on the cardiovascular system is essential to providing comprehensive medical care to patients receiving HCQ treatment.

Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS.

Acute kidney injury (AKI) is a common complication among patients with the novel coronavirus (COVID-19). COVID-19 along with AKI usually resulted in a poor prognosis for those affected. Remdesivir is a novel antiviral drug that was urgently approved for the treatment of COVID-19. In the current study, safety data of remdesivir were limited. We gathered information on COVID-19 cases in patients with adverse events that were reported to the U.S. Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. We employed the reporting odds ratio (ROR) method to perform disproportionality analysis. Finally, we identified 12,869 COVID-19 cases. A total of 3,991 of these cases reported remdesivir as a primary suspected drug, while 8,878 cases were treated with other drugs. More AKI events occurred in cases of male patients and those above the age of 65 years. We detected a significant association between remdesivir and AKI: ROR = 2.81, 95% CI (2.48, 3.18). The association was stronger after the propensity score matching ROR = 3.85, 95% CI (3.11, 4.78). The mean time to AKI event onset was 4.91 ± 7.25 days in COVID-19 cases with remdesivir therapy. The fatality proportion was 36.45% in AKI cases with remdesivir treatment. This pharmacovigilance study identified a significant association between AKI events and remdesivir treatment in COVID-19 patients by mining FAERS real-world big data. Although causality was not confirmed, the association between remdesivir and AKI should not be ignored, especially in the older, male COVID-19 inpatients.

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.

COVID-19: Imbalanced Immune Responses and Potential Immunotherapies.

The ongoing pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading and has resulted in grievous morbidity and mortality worldwide. Despite the high infectiousness of SARS-CoV-2, the majority of infected individuals are asymptomatic or have mild symptoms and could eventually recover as a result of their balanced immune function. On the contrary, immuno-compromised patients are prone to progress into severe or critical types underpinned by the entanglement of an overexuberant proinflammatory response and injured immune function. Therefore, well-coordinated innate and adaptive immune systems are pivotal to viral eradication and tissue repair. An in-depth understanding of the immunological processes underlying COVID-19 could facilitate rapidly identifying and choosing optimal immunotherapy for patients with severe SARS-CoV-2 infection. In this review, based on current immunological evidence, we describe potential immune mechanisms and discuss promising immunotherapies for COVID-19, including IL-6R blockades, convalescent plasma, intravenous gamma globulin, thymosin alpha1, corticosteroids, and type-I interferon, and recent advances in the development of COVID-19 vaccines.

Comparison of Liver Biomarkers in 288 COVID-19 Patients: A Mono-Centric Study in the Early Phase of Pandemic.

Background and Aims: Recent reports have indicated that hepatic dysfunction occurred in a proportion of patients with coronavirus disease 2019 (COVID-19). We aimed to compare and describe the liver biomarkers in different subtypes of COVID-19 patients. Methods: This study enrolled 288 COVID-19 patients in Huangshi Hospital of Traditional Chinese Medicine. All patients were divided into ordinary, severe, and critical groups according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Demographic, clinical characteristics and liver biomarkers were compared among the three groups. Results: During hospitalization, AST, TBiL, and ALP levels in ordinary and severe patients fluctuated within the normal range with a rising trend in critical patients except AST. ALT and GGT levels fluctuated within the normal range showing an upward trend, while LDH levels in the critical group exceeded the normal range. Prealbumin showed an upward trend, especially in the severe group. At discharge, AST and LDH levels in ordinary and severe groups were lower than their baselines but increased in the critical group. In contrast to albumin, TBiL levels were increased in ordinary and critical groups while decreased in the severe group. The stratified analysis revealed factors affecting liver function in critical cases included highest temperature ≥38.0°C, age ≥60 and symptom of hypoxemia. Conclusions: COVID-19 can cause severe hepatic dysfunction in critical patients, requiring early monitoring and intervention. LDH, ALP, GGT, TBiL, prealbumin, and albumin may be helpful for evaluating and predicting disease prognosis due to their correlation with disease severity in COVID-19.

Analysis of dynamic disturbance in blood coagulation function of patients with Coronavirus Disease 2019: A retrospective observational study.

Coronavirus Disease 2019 (COVID-19) has became a major problem affecting global health security.To assess the differences and dynamic changes of blood coagulation function in COVID-19 patients with different severity.A total of 261 COVID-19 patients from January 24 to March 25, 2020 in Huangshi, Hubei Province were enrolled.We designed a retrospective observational study. Clinical information, including age, blood routine and blood coagulation function, were collected. According to the Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China, patients were divided into 3 subgroups: 186 ordinary, 45 severe and 30 critical ones. We compared the differences in blood coagulation factors among groups.Average age in critical group (71.47 ±â€Š11.48 years) was the oldest of 3 subgroups. At admission, statistically differences could be observed among ordinary, severe and critical patients in D-dimer (0.18 ±â€Š0.33, 0.63 ±â€Š1.13 and 1.16 ±â€Š1.58 mg/L), fibrinogen/fibrin degradation products (FDP) (3.11 ±â€Š5.30, 9.82 ±â€Š23.91 and 21.94 ±â€Š40.98 µg/ml), platelet [(169 ±â€Š62.85), (188 ±â€Š71.56) and (117 ±â€Š38.31) × 10/L)] and lymphocyte count [(1.18 ±â€Š0.46), (0.82 ±â€Š0.35) and (0.75 ±â€Š0.39) × 10/L)], respectively (P < .05). During hospitalization, the peak values of coagulation and valley values of blood routine were monitored. There were significant differences among ordinary, severe and critical patients in D-dimer (0.26 ±â€Š0.46, 1.39 ±â€Š1.51 and 2.89 ±â€Š1.68 mg/L), FDP (3.29 ±â€Š5.52, 23.68 ±â€Š39.07 and 56.11 ±â€Š49.94 µg/ml), platelet [(164 ±â€Š55.53), (171 ±â€Š69.96) and (84 ±â€Š57.80) × 10/L)] and lymphocyte count [(1.10 ±â€Š0.46), (0.65 ±â€Š0.35) and (0.55 ±â€Š0.31) × 10/L)], respectively (P < .001). D-dimer and FDP in the course of disease in severe/critical groups showed a first upward and then downward trend.We concluded that coagulation function indexes such as D-dimer and FDP could be served as markers to estimate COVID-19 patients condition. Close monitoring of coagulation function may be helpful for early diagnosis of severe patients and guidance of treatments.