Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections.

Despite timely immunization programs, and efficacious vaccines conveying protection against SARS-CoV-2 infection, breakthrough infections in vaccinated individuals have been reported. The Delta variant of concern (VOC) outbreak in Guangzhou resulted in local transmission in vaccinated and non-vaccinated residents, providing a unique opportunity to study the protective effects of the inactivated vaccines in breakthrough infection. Here, we find that the 2-dose vaccinated group has similar peak viral titers and comparable speeds of viral RNA clearance to the non-vaccinated group but accelerated viral suppression in the middle course of the disease. We quantitatively demonstrate that peak viral pneumonia is significantly mitigated in the 2-dose vaccine group (median 0.298%) compared with the non-vaccinated (5.77%) and 1-dose vaccine (3.34%) groups. Pneumonia absorbance is approximately 6 days ahead in the 2-dose group (median 10 days) than in the non-vaccinated group (16 days) (p = 0.003). We also observe reduced cytokine inflammation and markedly undisturbed gene transcription profiles of peripheral blood mononuclear cells (PBMCs) in the 2-dose group. In short, our study demonstrates that prior vaccination substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery.

Cardiac involvement in patients recovering from Delta Variant of COVID-19: a prospective multi-parametric MRI study.

AIMS: The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID-19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID-19 based on multi-parametric cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS: We prospectively assessed patients recovering from Delta Variant of COVID-19 using multi-parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty-four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85-4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis-like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (-22.2 ± 2.8% vs. -24.6 ± 2.0%, P < 0.001) and global circumferential strain (-20.7 ± 6.8% vs. -24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement. CONCLUSIONS: The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac-related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant.

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China.

BACKGROUND: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. METHODS: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. FINDINGS: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). INTERPRETATION: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. FUNDING: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.

Longitudinal changes of laboratory measurements after discharged from hospital in 268 COVID-19 pneumonia patients.

BACKGROUND AND OBJECTIVE: Monitoring recovery process of coronavirus disease 2019 (COVID-19) patients released from hospital is crucial for exploring residual effects of COVID-19 and beneficial for clinical care. In this study, a comprehensive analysis was carried out to clarify residual effects of COVID-19 on hospital discharged patients. METHODS: Two hundred sixty-eight cases with laboratory measured data at hospital discharge record and five follow-up visits were retrospectively collected to carry out statistical data analysis comprehensively, which includes multiple statistical methods (e.g., chi-square, T-test and regression) used in this study. RESULTS: Study found that 13 of 21 hematologic parameters in laboratory measured dataset and volume ratio of right lung lesions on CT images highly associated with COVID-19. Moderate patients had statistically significant lower neutrophils than mild and severe patients after hospital discharge, which is probably caused by more efforts on severe patients and slightly neglection of moderate patients. COVID-19 has residual effects on neutrophil-to-lymphocyte ratio (NLR) of patients who have hypertension or chronic obstructive pulmonary disease (COPD). After released from hospital, female showed better performance in T lymphocytes subset cells, especially T helper lymphocyte% (16% higher than male). According to this sex-based differentiation of COVID-19, male should be recommended to take clinical test more frequently to monitor recovery of immune system. Patients over 60 years old showed unstable recovery process of immune cells (e.g., CD45 + lymphocyte) within 75 days after discharge requiring longer clinical care. Additionally, right lung was vulnerable to COVID-19 and required more time to recover than left lung. CONCLUSIONS: Criterion of hospital discharge and strategy of clinical care should be flexible in different cases due to residual effects of COVID-19, which depend on several impact factors. Revealing remaining effects of COVID-19 is an effective way to eliminate disorder of mental health caused by COVID-19 infection.

Application of 5G Technology to Conduct Real-Time Teleretinal Laser Photocoagulation for the Treatment of Diabetic Retinopathy.

Importance: Interest in teleophthalmology has been growing, especially during the COVID-19 pandemic. The advent of fifth-generation (5G) wireless systems has the potential to revolutionize teleophthalmology, but these systems have not previously been leveraged to conduct therapeutic telemedicine in the ophthalmology field. Objective: To assess the feasibility of 5G real-time laser photocoagulation as a telemedicine-based treatment for diabetic retinopathy (DR). Design, Setting, and Participants: This was a prospective study involving a retinal specialist from the Peking Union Medical College Hospital in Beijing, China, who performed online 5G real-time navigated retinal laser photocoagulation to treat participants with proliferative or severe nonproliferative DR who had been recruited in the Huzhou First People's Hospital in Zhejiang Province, China, located 1200 km from Beijing from October 2019 to July 2020. Interventions: These teleretinal DR and laser management procedures were conducted using a teleophthalmology platform that used the videoconference platform for teleconsultation, after which telelaser planning and intervention were conducted with a laser system and a platform for remote computer control, which were connected via 5G networks. Main Outcomes and Measures: Diabetic eye prognosis and the real-time laser therapy transmission speed were evaluated. Results: A total of 6 participants (9 eyes) were included. Six eyes were treated via panretinal photocoagulation alone, while 1 eye underwent focal/grid photocoagulation and 2 eyes underwent both panretinal photocoagulation and focal/grid photocoagulation. The mean (SD) age was 53.7 (13.6) years (range, 32-67 years). The mean (SD) duration of diabetes was 14.3 (6.4) years (range, 3-20 years). The mean (SD) logMAR at baseline was 0.32 (0.20) (20/30 Snellen equivalent). Retinal telephotocoagulation operations were performed on all eyes without any noticeable delay during treatment. The mean (SD) number of panretinal photocoagulation laser spots per eye in 1 session was 913 (243). Conclusions and Relevance: This study introduces a novel teleophthalmology paradigm to treat DR at a distance. Applying novel technologies may continue to ensure that remote patients with DR and other conditions have access to essential health care. Further studies will be needed to compare this approach with the current standard of care to determine whether visual acuity or safety outcomes differ.

Changes of quantitative CT-based airway wall dimensions in patients with COVID-19 during early recovery.

BACKGROUND: As the coronavirus disease 19 (COVID-19) pandemic evolves, the need for recognizing the structural pulmonary changes of the disease during early convalescence has emerged. Most studies focus on parenchymal destruction of the disease; but little is known about whether the disease affects the airway. This study was conducted to investigate the changes in airway dimensions and explore the associated factors during early convalescence in patients with COVID-19. METHODS: We retrospectively analyzed quantitative computed tomography (CT)-based airway measures of 69 patients with COVID-19 from 5 February to 17 March 2020, and 32 non-COVID-19 participants from 1 January 2018 to 31 December 2019 from Guangzhou, China. The well-established measures of wall area fraction and the square root of the wall area of a hypothetical bronchus with an inner perimeter of 10 mm, were used to describe airway wall dimensions. We described the characteristics of the dimensions and inner area of airways in 66 patients with COVID-19 at the initial and convalescent stages of the disease, and compared them with the non-COVID-19 group. Linear regression models were constructed to investigate the association of airway dimensions with duration of hospitalization or disease severity after recovery. Partial correlation coefficients were calculated to investigate whether inflammatory markers were related to airway dimensions. RESULTS: Among 66 patients with COVID-19, airway dimensions were greater during disease initiation than early convalescence, which was significantly greater than in non-COVID-19 participants. No significant difference was found between the patients with COVID-19 at the initial stage and the non-COVID-19 controls regarding the first to eighth generations of the inner area. In adjusted regression models, duration of hospitalization was negatively associated with wall area fraction of the first to the sixth generation of airways. No significant associations exist between airway dimensions and disease severity, or airway dimensions with inflammatory markers. CONCLUSIONS: Airway dimensions in patients with COVID-19 during disease initiation are greater than those in non-COVID-19 participants. Such structural airway changes continue to remain significantly greater during early convalescence. No evidence shows that disease severity or inflammatory markers are associated with airway dimensions, implying that the primary lesion attacked by COVID-19 might not be the airways.

Prognostic roles of KL-6 in disease severity and lung injury in COVID-19 patients: A longitudinal retrospective analysis.

To investigate the dynamic changes of Krebs von den Lungen-6 (KL-6) among patients with coronavirus disease 2019 (COVID-19) and the role of KL-6 as a noninvasive biomarker for predicting long-term lung injury, the clinical information and laboratory tests of 166 COVID-19 patients were collected, and a correlation analysis between KL-6 and other parameters was conducted. There were 17 (10.2%, 17/166) severe/critical and 149 (89.8%, 149/166) mild COVID-19 patients in our cohort. Serum KL-6 was significantly higher in severe/critical COVID-19 patients than in mild patients (median 898.0 vs. 451.2 U/ml, p < .001). KL-6 was next confirmed to be a sensitive and specific biomarker for distinguishing mild and severe/critical patients and correlate to computed tomography lung lesions areas. Serum KL-6 concentration during the follow-up period (>100 days postonset) was well correlated to those concentrations within 10 days postonset (Pearson r = .867, p < .001), indicating the prognostic value of KL-6 levels in predicting lung injury after discharge. Finally, elevated KL-6 was found to be significantly correlated to coagulation disorders, and T cells subsets dysfunctions. In summary, serum KL-6 is a biomarker for assessing COVID-19 severity and predicting the prognosis of lung injury of discharged patients.

Using artificial intelligence to assist radiologists in distinguishing COVID-19 from other pulmonary infections.

BACKGROUND: Accurate and rapid diagnosis of coronavirus disease (COVID-19) is crucial for timely quarantine and treatment. PURPOSE: In this study, a deep learning algorithm-based AI model using ResUNet network was developed to evaluate the performance of radiologists with and without AI assistance in distinguishing COVID-19 infected pneumonia patients from other pulmonary infections on CT scans. METHODS: For model development and validation, a total number of 694 cases with 111,066 CT slides were retrospectively collected as training data and independent test data in the study. Among them, 118 are confirmed COVID-19 infected pneumonia cases and 576 are other pulmonary infection cases (e.g. tuberculosis cases, common pneumonia cases and non-COVID-19 viral pneumonia cases). The cases were divided into training and testing datasets. The independent test was performed by evaluating and comparing the performance of three radiologists with different years of practice experience in distinguishing COVID-19 infected pneumonia cases with and without the AI assistance. RESULTS: Our final model achieved an overall test accuracy of 0.914 with an area of the receiver operating characteristic (ROC) curve (AUC) of 0.903 in which the sensitivity and specificity are 0.918 and 0.909, respectively. The deep learning-based model then achieved a comparable performance by improving the radiologists' performance in distinguish COVOD-19 from other pulmonary infections, yielding better average accuracy and sensitivity, from 0.941 to 0.951 and from 0.895 to 0.942, respectively, when compared to radiologists without using AI assistance. CONCLUSION: A deep learning algorithm-based AI model developed in this study successfully improved radiologists' performance in distinguishing COVID-19 from other pulmonary infections using chest CT images.

Clinical and radiologic features of the first cured Coronavirus disease 2019 (COVID-19) patient in Guangzhou City, China.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.

Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial.

BACKGROUND: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. METHODS: Our study (ClinicalTrials.gov: NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FINDINGS: This study successfully enrolled 86 patients with mild/moderate COVID-19, with 34 randomly assigned to receive LPV/r, 35 to arbidol, and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoint, the rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid, was similar between groups (all p > 0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest computed tomography (CT) at days 7 or 14 (all p > 0.05). At day 7, 8 (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group, and 2 (11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical (p = 0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. CONCLUSIONS: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FUNDING: This study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004, and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).

Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2.

BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People's Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18-86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1-6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3-4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient's history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.