Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

SARS-CoV-2 infection induces activation of ferroptosis in human placenta.

Ferroptosis, a regulated non-apoptotic form of cell death, has been implicated in the response to varied types of infectious agents including virus. In this study, we sought to determine whether SARS-CoV-2 infection can induce activation of ferroptosis in the human placenta. We collected placentas from 23 pregnant females with laboratory-confirmed SARS-CoV-2 following delivery and then used RNA in situ hybridization assay for detection of viral positive-sense strand (PSS) to confirm that these placentas have been infected. We also used immunohistochemistry assay to assess expression levels of acyl-CoA synthetase long-chain family member 4 (ACSL4), an essential executioner of ferroptosis in the same specimens. Our results showed that ACSL4 expression was significantly increased in the group with positive positive-sense strand staining compared to their negative counterparts (p = 0.00022). Furthermore, we found that there was a positive trend for increased PSS staining along with increased ACSL4 expression. Our study supports that ferroptosis is activated in the response to SARS-CoV-2 infection in the human placenta, highlighting a molecular mechanism potentially linking this coronavirus infection and pathogenesis of adverse pregnancy outcomes.

Effects and safety of auricular acupressure on depression and anxiety in isolated COVID-19 patients: A single-blind randomized controlled trial.

Objective: Psychological distress such as depression and anxiety resulted from coronavirus disease 2019 (COVID-19) have attracted increasing attention. The aim of this randomized controlled trial is to evaluate the effects and safety of auricular acupressure on depression and anxiety in isolated COVID-19 patients. Methods: 68 participants diagnosed with COVID-19 pneumonia (18-80 years old, SDS ≥ 50, SAS ≥ 45) were recruited and randomly allocated to the auricular acupressure group and the sham auricular acupressure group by a computer-generated random number sequence from 9th June to 30th June 2022. The group allocation was only blinded to the participants. Those in the auricular acupressure group were attached magnetic beads against 4 auricular points Shenmen, Subcortex, Liver and Endocrine, while sham group used four irrelevant auricular points. Outcomes were measured by Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Depression Scale (SAS) before and after treatment in both groups through electronic questionnaire in mobile phones. Results: After treatment, statistically significant differences were found in scores of SAS in both groups (P < 0.001 in auricular acupressure group; P = 0.003 in sham group), and SDS scores reduced significantly in the auricular acupressure group (P = 0.002). Significant reduced SAS and SDS scores were achieved in the auricular acupressure group than that in the sham group (F = 4.008, P = 0.049, MD -7.70 95% CI: -9.00, -6.40, SMD -2.79 95% CI: -3.47, -2.11 in SDS; F = 10.186, P = 0.002, MD -14.00 95% CI: -15.47, -12.53, SMD -4.46 95% CI: -5.37, -3.56 in SAS). No adverse events were found in either group during the whole study. Conclusion: Auricular acupressure is an effective and safe treatment for alleviating symptoms of depressive and anxiety in patients with COVID-19. Clinical trial registration: https://www.chictr.org.cn//, identifier ChiCTR2200061351.

A network view of human immune system and virus-human interaction.

The immune system is highly networked and complex, which is continuously changing as encountering old and new pathogens. However, reductionism-based researches do not give a systematic understanding of the molecular mechanism of the immune response and viral pathogenesis. Here, we present HUMPPI-2022, a high-quality human protein-protein interaction (PPI) network, containing > 11,000 protein-coding genes with > 78,000 interactions. The network topology and functional characteristics analyses of the immune-related genes (IRGs) reveal that IRGs are mostly located in the center of the network and link genes of diverse biological processes, which may reflect the gene pleiotropy phenomenon. Moreover, the virus-human interactions reveal that pan-viral targets are mostly hubs, located in the center of the network and enriched in fundamental biological processes, but not for coronavirus. Finally, gene age effect was analyzed from the view of the host network for IRGs and virally-targeted genes (VTGs) during evolution, with IRGs gradually became hubs and integrated into host network through bridging functionally differentiated modules. Briefly, HUMPPI-2022 serves as a valuable resource for gaining a better understanding of the composition and evolution of human immune system, as well as the pathogenesis of viruses.

Public Health and Investment Protection in the Context of the COVID-19 Pandemic-From the Sustainable Perspective of Exception Clauses

In response to the COVID-19 pandemic, various preventive and controlling measures have been taken by host states but may damage the interests of foreign investors and consequently result in international investment disputes. Confronted with potential international investment arbitration, the exceptions clause in international investment law is one of the host state's defences. However, the public health exception clause is a general exception clause with uncertainty when investment arbitration takes place and investment arbitral tribunals interpret it. In the international society, sustainable development has gradually been recognized as a key principle in contemporary international law. Against this background, in the context of international investment, it is appropriate for host states to optimize the exception clauses in BITs or FTAs, thereby reducing the risk of arbitration concerning the host state's regulatory measures to protect the public from the pandemic.

A SARS-CoV-2 Delta Variant Case Manifesting as Extensive Placental Infection and Fetal Transmission.

INTRODUCTION: Studies indicate a very low rate of SARS-CoV-2 detection in the placenta or occasionally a low rate of vertical transmission in COVID-19 pregnancy. SARS-CoV-2 Delta variant has become a dominant strain over the world and possesses higher infectivity due to mutations in its spike receptor-binding motif. CASE PRESENTATION: To determine whether SARS-CoV-2 Delta variant has increased potential for placenta infection and vertical transmission, we analyzed SARS-CoV-2 infection in the placenta, umbilical cord, and fetal membrane from a case where an unvaccinated mother and her neonate were COVID-19 positive. A 35-year-old primigravida with COVID-19 underwent an emergent cesarean delivery due to placental abruption in the setting of premature rupture of membranes. The neonate tested positive for SARS-CoV-2 within the first 24 h, and then again on days of life 2, 6, 13, and 21. The placenta exhibited intervillositis, increased fibrin deposition, and syncytiotrophoblast necrosis. Sequencing of viral RNA from fixed placental tissue revealed SAR-CoV-2 B.1.167.2 (Delta) variant. Both spike protein and viral RNA were abundantly present in syncytiotrophoblasts, cytotrophoblasts, umbilical cord vascular endothelium, and fetal membranes. CONCLUSION: We report with strong probability the first SARS-CoV-2 Delta variant transplacental transmission. Placental cells exhibited extensive apoptosis, senescence, and ferroptosis after SARS-CoV-2 Delta infection.

Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.

Presumed Recurrent MEWDS following Covid-19 Vaccination.

PURPOSE: To present an unusual case of recurrent multiple evanescent white dot syndrome (MEWDS) following the coronavirus 2019 (Covid-19) vaccination. METHODS: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS. RESULTS: A 49-year-old female who had MEWDS nine years ago presented to our clinic with blurred vision in her left eye. These symptoms occurred 2 days following Covid-19 vaccination. Fundus examinations and diagnostic testing were consistent with recurrent MEWDS. CONCLUSION: While rare, MEWDS can reoccur following Covid-19 vaccination.

Residual olfactory dysfunction in coronavirus disease 2019 patients after long term recovery.

INTRODUCTION: Hyposmia is among the most common symptoms of COVID-19 patients. Previous research has mainly described this issue at the disease's early stages. Because olfactory impairment can indicate neurological degeneration, we investigated the possibility of permanent olfactory damage by assessing hyposmia during the late recovery stage of COVID-19 patients. METHODS: Ninety-five patients were assessed with the Brief Smell Identification Test for Chinese (B-SITC) and Hyposmia Rating Scale (HRS) after 16 weeks from disease onset. Five weeks later, 41 patients were retested with B-SITC. RESULTS: At the first visit, hyposmia was identified in 26/82 (31.7%) and 22/95 (23.2%) of participants by HRS (HRS score ≤22) and B-SITC (B-SITC score <8), respectively. The rates of hyposmia in patients who performed B-SITC after 14-15 weeks, 16-17 weeks, and ≥18 weeks from disease onset were 7/25 (28%), 8/35 (23%) and 7/35 (20%), respectively, which demonstrated a trend of olfaction improvement as recovery time prolonging. Hyposmia percentages decreased from the first visit (34.1%) to the second visit (24.4%) for the 41 patients who completed 2 visits. B-SITC scores of the first-visit hyposmia participants increased significantly at the second visit (5.29 ± 2.02 to 8.29 ± 2.40; n = 14, P = 0.001). Severe cases tended to recover less than common cases. CONCLUSIONS: Hyposmia was present in up to one-third of COVID-19 patients after about 3 months from disease onset. Notable recovery of olfactory function was observed at a next 5-weeks follow-up. Clinical severity had little influence on olfactory impairment and recovery.

Features of Cytokine Storm Identified by Distinguishing Clinical Manifestations in COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by a new coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently spreading all over the world. In this paper, we developed a practical model for identifying the features of cytokine storm, which is common in acute infectious diseases and harmful manifestation of COVID-19, by distinguishing major and minor clinical events. This model is particularly suitable for identifying febrile and infectious diseases like COVID-19. Based on this model, features of cytokine storm and pathogenesis of COVID-19 have been proposed to be a consequence of the disequilibrated cytokine network resulting from increased biological activity of transforming growth factor-ß (TGF-ß), which induces certain clinical manifestations such as fatigue, fever, dry cough, pneumonia, abatement and losing of olfactory, and taste senses in some patients. Research and clarification of the pathogenesis of COVID-19 will contribute to precision treatment. Various anti-TGF-ß therapies may be explored as potential COVID-19 treatment. This novel model will be helpful in reducing the widespread mortality of COVID-19.

Synchronized nonpharmaceutical interventions for the control of COVID-19.

The world is experiencing an ongoing pandemic of coronavirus disease-2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In attempts to control the pandemic, a range of nonpharmaceutical interventions (NPIs) has been implemented worldwide. However, the effect of synchronized NPIs for the control of COVID-19 at temporal and spatial scales has not been well studied. Therefore, a meta-population model that incorporates essential nonlinear processes was constructed to uncover the transmission characteristics of SARS-CoV-2 and then assess the effectiveness of synchronized NPIs on COVID-19 dynamics in China. Regional synchronization of NPIs was observed in China, and it was found that a combination of synchronized NPIs (the travel restrictions, the social distancing and the infection isolation) prevented 93.7% of SARS-CoV-2 infections. The use of synchronized NPIs at the time of the Wuhan lockdown may have prevented as much as 38% of SARS-CoV-2 infections, compared with the unsynchronized scenario. The interconnectivity of the epicenter, the implementation time of synchronized NPIs, and the number of regions considered all affected the performance of synchronized NPIs. The results highlight the importance of using synchronized NPIs in high-risk regions for the control of COVID-19 and shed light on effective strategies for future pandemic responses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11071-021-06505-0.

Intervention of adolescent' mental health during the outbreak of COVID-19 using aerobic exercise combined with acceptance and commitment therapy.

Objective: To explore the intervention effect of aerobic exercise in combination with acceptance and commitment therapy on mental health of adolescents during the outbreak of COVID-19 based on the theory of the dual-factor model of mental health. Methodology: 1200 adolescents aged 12-19 in Fujian Province, China were screened by means of the dual-factor model of mental health from March to April 2020. 30 vulnerable, 30 symptomatic but contented and 30 distressed adolescents were selected as the experiment objects, and these 3 types of adolescents were randomly divided into the intervention group and the control group. Among them, the intervention group received 8 weeks of aerobic exercise in combination with acceptance and commitment therapy, 3 times a week, about 40-60 min each time. The control group, however, didn't receive any intervention other than routine mental health education. Measurements were made before and after the intervention. Results: (1) For vulnerable, symptomatic but contented and distressed individuals, before the intervention, there is no significant difference between the intervention group and the control group in terms of psychological distress, well-being and psychological flexibility (P > 0.05). After the intervention, psychological distress and experiential avoidance is significantly lower in the intervention group than in the control group, but all dimensions of well-being is significantly higher in the intervention group than in the control group (P < 0.05). (2) For vulnerable, symptomatic but contented and distressed individuals, before and after the intervention, there are significant differences in psychological distress, well-being and psychological flexibility of the intervention group (P < 0.05), but there are no significant differences in the control group (P > 0.05). Conclusion: Attention should be paid to the problems of mental health of adolescents caused by the sudden outbreak of public health incidents. Aerobic exercise in combination with acceptance and commitment therapy is feasible and effective for the intervention in mental health of adolescents.

Spatial and temporal differentiation of COVID-19 epidemic spread in mainland China and its influencing factors.

This paper uses the exploratory spatial data analysis and the geodetector method to analyze the spatial and temporal differentiation characteristics and the influencing factors of the COVID-19 (corona virus disease 2019) epidemic spread in mainland China based on the cumulative confirmed cases, average temperature, and socio-economic data. The results show that: (1) the epidemic spread rapidly from January 24 to February 20, 2020, and the distribution of the epidemic areas tended to be stable over time. The epidemic spread rate in Hubei province, in its surrounding, and in some economically developed cities was higher, while that in western part of China and in remote areas of central and eastern China was lower. (2) The global and local spatial correlation characteristics of the epidemic distribution present a positive correlation. Specifically, the global spatial correlation characteristics experienced a change process from agglomeration to decentralization. The local spatial correlation characteristics were mainly composed of the'high-high' and 'low-low' clustering types, and the situation of the contiguous layout was very significant. (3) The population inflow from Wuhan and the strength of economic connection were the main factors affecting the epidemic spread, together with the population distribution, transport accessibility, average temperature, and medical facilities, which affected the epidemic spread to varying degrees. (4) The detection factors interacted mainly through the mutual enhancement and nonlinear enhancement, and their influence on the epidemic spread rate exceeded that of single factors. Besides, each detection factor has an interval range that is conducive to the epidemic spread.

Statistical Issues and Recommendations for Clinical Trials Conducted During the COVID-19 Pandemic.

Abstract-The COVID-19 pandemic has had and continues to have major impacts on planned and ongoing clinical trials. Its effects on trial data create multiple potential statistical issues. The scale of impact is unprecedented, but when viewed individually, many of the issues are well defined and feasible to address. A number of strategies and recommendations are put forward to assess and address issues related to estimands, missing data, validity and modifications of statistical analysis methods, need for additional analyses, ability to meet objectives and overall trial interpretability.

Characteristics of disease progress in patients with coronavirus disease 2019 in Wuhan, China.

Coronavirus disease 2019 (COVID-19) patients were classified into four clinical stages (uncomplicated illness, mild, severe and critical pneumonia) depending on disease severity. We aim to investigate the corresponding clinical, radiological and laboratory characteristics between different clinical stages. A retrospective, single-centre study of 101 confirmed patients with COVID-19 at Renmin Hospital of Wuhan University from 2 January to 28 January 2020 was enrolled; follow-up endpoint was on 8 February 2020. Clinical data were collected and compared during the course of illness. The median age of the 101 patients was 51.0 years and 33.6% were medical staff. Fever (68%), cough (50%) and fatigue (23%) are the most common symptoms. About 26% patients underwent the mechanical ventilation and 98% patients were treated with antibiotics. Thirty-seven per cent patients were cured and 11 died. On admission, the number of patients with uncomplicated illness, mild, severe and critical pneumonia were 2 [2%], 86 [85%], 11 [11%] and 2 [2%]. Forty-four of the 86 mild pneumonia progressed to severe illness within 4 days, with nine patients worsened due to critical pneumonia within 4 days. Two of the 11 severe patients improved to mild condition while three others deteriorated. Significant differences were observed among groups of different clinical stages in numbers of influenced pulmonary segments (6 vs. 12 vs. 17, P < 0.001). A significantly upward trend was witnessed in ground-glass opacities overlapped with striped shadows (33% vs. 42% vs. 55% vs. 80%, P < 0.001), while pure ground-glass opacities gradually decreased as disease progressed (45% vs. 35% vs. 24% vs. 13%, P < 0.001) within 12 days. Lymphocytes, prealbumin and albumin showed a downtrend as disease progressed from mild to severe or critical condition, an uptrend was found in white blood cells, C-reactive protein, neutrophils and lactate dehydrogenase. The proportions of serum amyloid A > 300 mg/l in mild, severe and critical conditions were 18%, 46% and 71%, respectively.

Impact of population movement on the spread of 2019-nCoV in China.

Since Dec 2019, China has experienced an outbreak caused by a novel coronavirus, 2019-nCoV. A travel ban was implemented for Wuhan, Hubei on Jan 23 to slow down the outbreak. We found a significant positive correlation between population influx from Wuhan and confirmed cases in other cities across China (R2 = 0.85, P < 0.001), especially cities in Hubei (R2 = 0.88, P < 0.001). Removing the travel restriction would have increased 118% (91%-172%) of the overall cases for the coming week, and a travel ban taken three days or a week earlier would have reduced 47% (26%-58%) and 83% (78%-89%) of the early cases. We would expect a 61% (48%-92%) increase of overall cumulative cases without any restrictions on returning residents, and 11% (8%-16%) increase if the travel ban stays in place for Hubei. Cities from Yangtze River Delta, Pearl River Delta, and Capital Economic Circle regions are at higher risk.