Patterns and predictors of adolescent life change during the COVID-19 pandemic: a person-centered approach.

The present study investigated patterns of adolescent life changes across multiple life domains and utilized a holistic-interactionistic perspective to examine their individual, familial, and societal correlates with a sample of 2544 Chinese parent-adolescent dyads. Adolescents were aged from 10 to 19 years old (50.16% girls). Latent profile analysis revealed five life change profiles, including three improved profiles at various degrees, one unchanged profile, and one worsened profile. The majority of adolescents had an improved or unchanged life. Multinomial logistic regression analyses found that most of the individual, familial, and societal factors predicted the group memberships. Notably, parent-adolescent conflict was a significant factor that predicted memberships of all patterns. These findings show the resilience of adolescents and indicate the need for policies and interventions that consider the holistic nature of adolescents' person-context system, especially during a global crisis such as the COVID-19 pandemic.

Structural insights into broadly neutralizing antibodies against SARS-CoV-2 elicited by hybrid immunity.

Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II or III bNAbs with new epitopes mapped to receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis.

A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.

The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.

Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice.

SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.

Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19.

Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19. Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.

Impact of COVID-19 Outbreak on the Gynecological Outpatients HPV Infection Rate in Wuhan, China: A Retrospective Observational Study.

Background: The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has caused millions of deaths and greatly influenced the timely diagnosis and treatment of other diseases. Throughout the pandemic, there was a dramatic reduction in the prevalence of several sexually transmitted infections. However, the impact of the ongoing pandemic on human papillomavirus (HPV) infection rates has not been investigated thus far. Materials and Methods: We retrospectively collected data regarding HPV and cervical cancer screening results of outpatients from gynecological clinics of a tertiary hospital from 1 December 2018 to 31 December 2020 in Wuhan. Based on the timeline of the SARS-CoV-2 pandemic in Wuhan, we divided this period into four relatively independent stages to compare the HPV screening visit numbers and infection rates. Results: There was a 50% drop in HPV screening visits and a 10% drop in HPV infection rates throughout the pandemic when compared with the numbers collected before the pandemic. Strict lockdown measures greatly decreased the HPV infection rate (17.03 vs. 8.29, P = 0.003). During the pandemic, the most prevalent HPV genotypes were HPV 16, 52, 58, and 53. After the pandemic, the HPV infection rate recovered quickly, but it was still slightly lower than the infection rate found before the outbreak (23.3 vs. 21.2%). Conclusion: During coronavirus disease 2019 (COVID-19) pandemic, cervical cancer screening visits and HPV infection rates have decreased dramatically. The HPV transmission has also decreased after strict lockdown. Effective HPV and cervical cancer screening programs should be strengthened immediately to reduce the transmission of HPV during and after the pandemic.

Clinical Features and Laboratory Examination to Identify Severe Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: With the COVID-19 epidemic breakout in China, up to 25% of diagnosed cases are considered to be severe. To effectively predict the progression of COVID-19 via patients' clinical features at an early stage, the prevalence of these clinical factors and their relationships with severe illness were assessed. METHODS: In this study, electronic databases (PubMed, Embase, Web of Science, and Chinese database) were searched to obtain relevant studies, including information on severe patients. Publication bias analysis, sensitivity analysis, prevalence, sensitivity, specificity, likelihood ratio, diagnosis odds ratio calculation, and visualization graphics were achieved through software Review Manager 5.3, Stata 15, Meta-DiSc 1.4, and R. RESULTS: Data of 3.547 patients from 24 studies were included in this study. The results revealed that patients with chronic respiratory system diseases (pooled positive likelihood 6.07, 95% CI: 3.12-11.82), chronic renal disease (4.79, 2.04-11.25), cardiovascular disease (3.45, 2.19-5.44), and symptoms of the onset of chest tightness (3.8, 1.44-10.05), shortness of breath (3.18, 2.24-4.51), and diarrhea (2.04, 1.38-3.04) exhibited increased probability of progressing to severe illness. C-reactive protein, ratio of neutrophils to lymphocytes, and erythrocyte sedimentation rate increased a lot in severe patients compared to nonsevere. Yet, it was found that clinical features including fever, cough, and headache, as well as some comorbidities, have little warning value. CONCLUSIONS: The clinical features and laboratory examination could be used to estimate the process of infection in COVID-19 patients. The findings contribute to the more efficient prediction of serious illness for patients with COVID-19 to reduce mortality.

The high diversity of SARS-CoV-2-related coronaviruses in pangolins alerts potential ecological risks.

Understanding the zoonotic origin and evolution history of SARS-CoV-2 will provide critical insights for alerting and preventing future outbreaks. A significant gap remains for the possible role of pangolins as a reservoir of SARS-CoV-2 related coronaviruses (SC2r-CoVs). Here, we screened SC2r-CoVs in 172 samples from 163 pangolin individuals of four species, and detected positive signals in muscles of four Manis javanica and, for the first time, one M. pentadactyla. Phylogeographic analysis of pangolin mitochondrial DNA traced their origins from Southeast Asia. Using in-solution hybridization capture sequencing, we assembled a partial pangolin SC2r-CoV (pangolin-CoV) genome sequence of 22 895 bp (MP20) from the M. pentadactyla sample. Phylogenetic analyses revealed MP20 was very closely related to pangolin-CoVs that were identified in M. javanica seized by Guangxi Customs. A genetic contribution of bat coronavirus to pangolin-CoVs via recombination was indicated. Our analysis revealed that the genetic diversity of pangolin-CoVs is substantially higher than previously anticipated. Given the potential infectivity of pangolin-CoVs, the high genetic diversity of pangolin-CoVs alerts the ecological risk of zoonotic evolution and transmission of pathogenic SC2r-CoVs.

Facilities for Centralized Isolation and Quarantine for the Observation and Treatment of Patients with COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic increased the burden on many healthcare systems and in the process, exposed the need for medical resources and physical space. While few studies discussed the efficient utilization of medical resources and physical space so far. Therefore, this study aimed to summarize experiences related to facilities used for centralized isolation for medical observation and treatment during the COVID-19 pandemic in China and to provide suggestions to further improve the management of confirmed cases, suspected cases, and close contacts. In China, three types of facilities for centralized isolation (Fangcang shelter hospitals, refitted non-designated hospitals, and quarantine hotels) underwent retrofitting for the treatment and isolation of confirmed and suspected cases. These facilities mitigated the immediate high demand for space. Moreover, in order to minimize infection risks in these facilities, regulators and governmental agencies implemented new designs, management measures, and precautionary measures to minimize infection risk. Other countries and regions could refer to China's experience in optimally allocating social resources in response to the COVID-19 pandemic. As a conclusion, government should allocate social resources and construct centralized isolation and quarantine facilities for an emergency response, health authorities should issue regulations for centralized isolation facilities and pay strict attention to the daily management of these facilities, a multidisciplinary administration team is required to support the daily operation of a centralized isolation facility, in-depth studies and international collaboration on the centralized isolation policy are encouraged.

Prevention and control of coronavirus disease 2019 (COVID-19) in public places.

Public places favor the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) due to dense population, large personal mobility, and higher contact opportunities. In order to protect the health of general public in operating public places during COVID-19 pandemic, this study proposed general precautions and control strategies from perspective of operation management, social distancing, cleaning and disinfection, and personal protection. In addition, with regard of risk level, specific precautions and control strategies were proposed for living service places, outdoor places, and confined places. The comprehensive application of above recommendations could effectively interrupt the spread of COVID-19, and protect the health of general public in public places. This study proposed general and specific precautions and control strategies in public places during COVID-19, and suggested further improvement of pandemic response.

CT features of COVID-19 patients with two consecutive negative RT-PCR tests after treatment.

The objective of this study is to expound the CT features of COVID-19 patients whose throat swab samples were negative for two consecutive nucleic acid tests after treatment. We retrospectively reviewed 46 COVID-19 patients with two consecutive negative RT-PCR tests after treatment. The cases were divided into moderate group and severe/critical group according to disease severity. Clinical and CT scanning data were collected. CT signs of pulmonary lesions and the score of lung involvement were expounded. Thirty-nine moderate cases and seven severe/critical cases were included. Residual pulmonary lesions were visible in CT images. Moderate patients showed peripheral lesions while severe/critical cases exhibited both central and peripheral lesions with all lobes involvement. Mixed ground glass opacity (GGO) and pulmonary consolidation were noted. A larger proportion of severe patients showed reticular pulmonary interstitium thickening. Air bronchogram, pleural effusion, vascular enlargement, bronchial wall thickening, bronchiectasis, pleural thickening and pleural adhesion were more frequently observed in severe/critical group. The severe/critical group showed higher CT score. Pulmonary lesions persisted even after twice consecutive negative nucleic acid tests. We strongly recommended regular follow-up of CT scans after nucleic acid tests conversion. Evaluation of complete remission should base on chest CT.

Prevention and control of COVID-19 in public transportation: Experience from China.

Due to continuous spread of coronavirus disease 2019 (COVID-19) worldwide, long-term effective prevention and control measures should be adopted for public transport facilities, as they are increasing in popularity and serve as the principal modes for travel of many people. The human infection risk could be extremely high due to length of exposure time window, transmission routes and structural characteristics during travel or work. This can result in the rapid spread of the infection. Based on the transmission characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the nature of public transport sites, we identified comprehensive countermeasures toward the prevention and control of COVID-19, including the strengthening of personnel management, personal protection, environmental cleaning and disinfection, and health education. Multi-pronged strategies can enhance safety of public transportation. The prevention and control of the disease during the use of public transportation will be particularly important when all countries in the world resume production. The aim of this study is to introduce experience of the prevention and control measures for public transportation in China to promote the global response to COVID-19.

Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.

The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19.

Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+TFH cell differentiation together with an increase in T-bet+TH1 cells and aberrant extra-follicular TNF-a accumulation.  Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections and suggest that achieving herd immunity through natural infection may be difficult. Funding: This work was supported by NIH U19 AI110495 to SP, NIH R01 AI146779 to AGS, NIH R01AI137057 and DP2DA042422 to DL, BMH was supported by NIGMS T32 GM007753, TMC was supported by T32 AI007245. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged. Conflict of Interest: None. Ethical Approval: This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women's Hospital.