Long-Term Follow-Up Study of COVID-19: Evaluation on Thin-Slice CT.

Purpose: To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge. Patients and Methods: A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher's exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0. Results: There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe-critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient's condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%). Conclusion: The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients' age and disease conditions were positively correlated with residual lesions.

SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.

A deficiency of the functional α7 nicotinic acetylcholine receptor (α7nAChR) impairs neuronal and immune systems. The SARS-CoV-2 spike protein (S12) facilitates virus cell entry during COVID-19 infection and can also independently disrupt cellular functions. Here, we found that S12 expression significantly downregulated surface expression of α7nAChR in mammalian cells. A helical segment of S12 (L1145-L1152) in the spike neck was identified to be responsible for the downregulation of α7nAChR, as the mutant S12AAA (L1145A-F1148A-L1152A) had minimal effects on surface α7nAChR expression. This S12 segment is homologous to the α7nAChR intracellular helical motif known for binding chaperone proteins RIC3 and Bcl-2 to promote α7nAChR surface expression. Competition from S12 for binding these proteins likely underlies suppression of surface α7nAChR. Considering the critical roles of α7nAChR in cellular functions, these findings provide a new perspective for improving mRNA vaccines and developing treatment options for certain symptoms related to long COVID.

Caregiver Perceptions of Children's and Adolescents' Psychosocial Functioning During the Stringent COVID-19 Lockdown Restrictions in Shanghai: Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic represents a global health crisis. The Shanghai municipal government in China implemented strict and comprehensive pandemic control strategies in the first half of 2022 to eliminate a wave of COVID-19 infection. The pandemic and the resulting government responses have led to abrupt changes to families' daily lives, including the mental health of children and adolescents. OBJECTIVE: The aim of this paper is to examine the impact of COVID-19 exposure and the stringent lockdown measures on the daily life and mental health of children and adolescents and to provide suggestions on maintaining their mental health when similar public health emergencies occur in the future. METHODS: In this cross-sectional study, an anonymous survey was distributed online in May 1-15, 2022, in Shanghai. Individuals were eligible to participate if they were currently the caregiver of a child or adolescent (aged 4-17 years). Outcomes were psychosocial functioning of children and adolescents, as reported by parents, using the Pediatric Symptom Checklist-17. COVID-19 exposure and life changes were also reported. Multivariate logistic regression was used to analyze risk factors for poor psychosocial functioning. RESULTS: In total, 2493 valid questionnaires were analyzed. The rate of positive scores on the global Pediatric Symptom Checklist-17 scale was 16.5% (n=411). Internalizing, attention, and externalizing problem subscale positivity rates were 17.3% (n=431), 10.9% (n=272), and 8.9% (n=221), respectively. Caregivers reported that 64.2% (n=1601) and 20.7% (n=516) of the children's interactions with friends or peers and parents deteriorated, respectively. Compared with male caregivers, female caregivers were less likely to report psychosocial problems in children and adolescents (adjusted odds ratio [aOR] 0.68; 95% CI 0.53-0.88). Older children and those with lower COVID-19 Exposure and Family Impact Scales scores were less likely to have psychological problems (aOR 1.15; 95% CI 1.10-1.21). Compared with children with screen times <1 hour per day for recreation, those using screens for >3 hours had higher odds of psychological distress (aOR 2.09; 95% CI 1.47-1.97). Children who spent 1-2 hours exercising and had better interactions with friends or peers and parents showed a trend toward lower odds of psychological problems. Children and adolescents with worse sleep compared with preclosure were more likely to have psychological problems. CONCLUSIONS: The prevalence of psychosocial problems among children and adolescents is relatively high. Being young, having more COVID-19 exposure, and having more screen times (>3 h/day), less exercise time (<30 min), worse sleep, and deteriorated interactions with friends or peers and parents were risk factors for poor psychosocial functioning. It is necessary for governments, communities, schools, and families to take appropriate countermeasures to reduce the negative impact of the stringent control measures on caregivers' parenting and psychosocial functioning of children and adolescents.

Weighted gene co-expression network-based identification of genetic effect of mRNA vaccination and previous infection on SARS-CoV-2 infection.

To investigate the effect conferred by vaccination and previous infection against SARS-CoV-2 infection in molecular level, weighted gene co-expression network analysis was applied to screen vaccination, prior infection and Omicron infection-related gene modules in 46 Omicron outpatients and 8 controls, and CIBERSORT algorithm was used to infer the proportions of 22 subsets of immune cells. 15 modules were identified, where the brown module showed positive correlations with Omicron infection (r = 0.35, P = 0.01) and vaccination (r = 0.62, P = 1 × 10-6). Enrichment analysis revealed that LILRB2 was the unique gene shared by both phosphatase binding and MHC class I protein binding. Pathways including "B cell receptor signaling pathway" and "FcγR-mediated phagocytosis" were enriched in the vaccinated samples of the highly correlated LILRB2. LILRB2 was also identified as the second hub gene through PPI network, after LCP2. In conclusion, attenuated LILRB2 transcription in PBMC might highlight a novel target in overcoming immune evasion and improving vaccination strategies.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

Good Personality and Subjective Well-Being During the COVID-19 Pandemic: A Three-Wave Longitudinal Study in Chinese Contexts.

Numerous studies have emphasized the importance of examining psychological distress during the COVID-19 pandemic. It is important to identify the factors that affect the influence of COVID-19 on people's mental health. The present research was a three-wave longitudinal study (N = 1495) examining the concurrent and prospective relations of good personality with subjective well-being during the COVID-19 pandemic. Results showed that good personality positively predicted the subsequent well-being after controlling for the respective autoregressive effects and Big Five personality traits. Specifically, individuals who scored higher on measures of good personality tended to maintain higher well-being in the face of COVID-19. However, subjective well-being could positively predict subsequent personality only at the first time point. In addition, the prospective effect of good personality on subjective well-being was greater than the reverse effect. These findings support the opinion that as a positive value orientation in personality, good personality has a significant positive impact on the response to the pandemic situation.

Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Beijing, China.

A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis-based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV-A replaced RSV-B in July 2021 to become the dominant subtype. Six RSV-A and eight RSV-B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.

Effect of social media overload on college students' academic performance under the COVID-19 quarantine.

Features and relevant services of online social media have been attracting users during the COVID-19 pandemic. Previous studies have shown that college students tend to use social media more frequently than other groups. However, in being affected by social media overload, the social media use behaviors of many college students have been out of their control in terms of their capabilities or cognition. Based on the stressor-strain-outcome (SSO) model and the theory of compensatory internet use (TCIU), we developed a research model to study the causes of social media overload and its impact on college students' academic performance during the COVID-19 pandemic. A total of 441 valid responses from college students through questionnaires in China are collected via purposive sampling and used in the data analysis. This study conducts PLS-SEM to analyze collected data, finding that boredom proneness is associated with overload (stress), which has a bearing on social media overload (strain) and the reduction in final performance (outcome). Through illustrating the psychological and behavioral conditions that hinder the academic performance of students, this study provides deeper insights into students' uncontrollable use of social media. Moreover, with respect to the identified antecedents, this study aims to find solutions to mitigate the impact of social media overload resulting from boredom proneness on the academic performance of college students.

Multiplex Fragment Analysis for Flexible Detection of All SARS-CoV-2 Variants of Concern.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and effective tracking requires rapid return of results. Surveillance of variants is typically performed by whole genome sequencing (WGS), which can be financially prohibitive and requires specialized equipment and bioinformatic expertise. Genotyping approaches are rapid methods for monitoring SARS-CoV-2 variants but require continuous adaptation. Fragment analysis may represent an approach for improved SARS-CoV-2 variant detection. METHODS: A multiplex fragment analysis approach (CoVarScan) was validated using PCR targeting variants by size and fluorescent color. Eight SARS-CoV-2 mutational hot spots in variants of concern (VOCs) were targeted. Three primer pairs (recurrently deleted region [RDR] 1, RDR2, and RDR3-4) flank RDRs in the S-gene. Three allele-specific primers target recurrent spike receptor binding domain mutants. Lastly, 2 primer pairs target recurrent deletions or insertions in ORF1A and ORF8. Fragments were resolved and analyzed by capillary electrophoresis (ABI 3730XL), and mutational signatures were compared to WGS results. RESULTS: We validated CoVarScan using 3544 clinical respiratory specimens. The assay exhibited 96% sensitivity and 99% specificity compared to WGS. The limit of detection for the core targets (RDR1, RDR2, and ORF1A) was 5 copies/reaction. Variants were identified in 95% of samples with cycle threshold (CT) <30 and 75% of samples with a CT 34 to 35. Assay design was frozen April 2021, but all subsequent VOCs have been detected including Delta (n = 2820), Mu, (n = 6), Lambda (n = 6), and Omicron (n = 309). Genotyping results are available in as little as 4 h. CONCLUSIONS: Multiplex fragment analysis is adaptable and rapid and has similar accuracy to WGS to classify SARS-CoV-2 variants.

High-performance electret and antibacterial meltblown nonwovens doped with nanoparticles of boehmite and ZnO for air filtration (preprint)

The current pandemic caused by Covid-19 triggered intensively the development of high-performance air filters. Polypropylene (PP) is widely used as the raw material of meltblown nonwovens that is the core layer in air filters, such as, masks. In this study, an electret PP meltblown nonwoven with antibacterial activity was developed, and nano boehmite (AlOOH) and nano-ZnO employed as electret and antibacterial agent, respectively. 0.5-2.0 wt% of AlOOH and 1.0 wt% of ZnO were doped into PP matrix using a twin-screw extruder and the resulting masterbatches applied as raw materials to afford nonwovens via a meltblown process. The as-prepared nonwovens were characterized by means of SEM, IR and DSC/TG, and after corona charging, the filtration efficiency, charge decay and antibacterial properties were evaluated. More than 1.0 wt% dosage of AlOOH endowed the nonwoven with high filtration efficiency and 1.0 wt% of ZnO brought about antibacterial activity. Corona charging was an effective means to make the nonwovens electret charged and the charges were quicker to decay in air than in a sealed bag. The as-prepared meltblown nonwoven would be a remarkably promising filter in air filtration.

The Epidemiology of COVID-19 and MS-Related Characteristics in a National Sample of People With MS in China.

Few studies have focused on immune status and disease activity in MS patients during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to investigate immune status, COVID-19 infection, and attacks in MS patients during the pandemic. An online questionnaire about COVID-19 infection, MS attack, and MS treatment during the pandemic was administered to all 525 MS patients registered in our hospital database from January 1, 2011, to June 1, 2020. Only 384 responded, of which 361 patients could be included in the final analysis. During the pandemic, 42.1% of the 361 patients and 65.0% of the 234 patients on immunotherapies were exposed to teriflunomide. Compared to patients who didn't receive treatment, patients exposed to DMTs had significantly lower levels of neutrophils (P < 0.01) and immunoglobulin G (P < 0.01), and patients exposed to immunosuppressants had significantly lower levels of immunoglobulin G (P < 0.05). Over 80% of our patients followed effective protective measures and none of the 361 MS patients in our cohort contracted COVID-19. Patients whose treatment was disrupted had a significantly higher annualized relapse rate (ARR) during than before the pandemic (P < 0.01), while the ARR of patients with continuous treatment or without treatment remained unchanged. During the pandemic, the risk of MS attack due to treatment disruption possibly outweighs the risk of COVID-19 infection under preventive measures, and MS treatment maintenance might be necessary.

Characteristic of Parkinson's disease with severe COVID-19: a study of 10 cases from Wuhan.

Information about Parkinson's disease (PD) patients with severe COVID-19 is scarce. We aimed to analyze the clinical characteristics, outcomes, and risk factors affecting the prognosis of PD patients with severe COVID-19 infection. Clinical data of severe COVID-19 patients admitted at the Union Hospital, Wuhan between 28th January and 29th February 2020 were collected and analyzed. 10 patients (1.96%) had a medical history of PD with a mean (SD) age of 72.10 (± 11.46) years. The clinical characteristics and outcomes of severe COVID-19 with and without PD patients were then compared. There was no significant difference in overall mortality between the PD and non-PD patients with severe COVID-19 (p > 0.05). In PD patients with severe COVID-19, the proportion of patients with critical type, disturbance of consciousness, incidence of complications, white blood cells count and neutrophils counts on admission seem higher in the non-survivors. PD patients with older age, longer PD duration, and late stage PD may be highly susceptible to critical COVID-19 infection and bad outcome. The PD patients with consciousness disorders and complications that progressed rapidly are at increased risk of death.

Knowledge of and attitudes toward COVID-19 among parents of child dental patients during the outbreak

Abstract: The aim of this study was to evaluate the knowledge of and attitudes toward coronavirus disease 2019 (COVID-19) among the parents of child dental patients in Shenzhen during the outbreak. A structured questionnaire containing 10 questions was used, and each question had 2 or 3 possible answers. The parents of children (aged 0-14 years) who visited the dental department of our hospital last year were eligible to participate in this study. A total of 148 parents were interviewed by telephone in February 2020 by research staff. A total of 94.59% of the parents said they paid high attention to COVID-19 and explained it to their children;66.22% thought the dental department environment was more dangerous than other public places;91.89% believed the dental department had a higher risk of virus infection;and 83.78% said they would take their children to a dental department if the children had a severe toothache. Approximately 81.08% of the parents expressed confidence after we informed them about the preventive measures taken in the dental department to ensure safe treatment for their children. In conclusion, all parents were concerned about COVID-19, and most of them had talked about it with their children often. In addition, a considerable percentage of them would not take their children to the dental department even if they had severe dental pain and thought that the dental environment could be more dangerous than other environments. More information about this topic should be delivered to this population.

Effects of four types of integrated Chinese and Western medicines for the treatment of COVID-19 in China: a network meta-analysis

SUMMARY OBJECTIVE Various integrated Chinese and Western medicines might be beneficial for the treatment of Coronavirus disease 2019 (COVID-19). This study aims to evaluate the efficacy of lung computed tomography (CT) of four integrated Chinese and Western medicines in the treatment of COVID-19 using network meta-analysis (NMA). METHODS Multiple databases were consulted to find randomized controlled trials of four different types of integrated Chinese and Western medicines for the treatment of COVID-19. NMA was conducted on the data using Stata (13.0) software. The odds ratio (OR) was calculated. The studies included in this paper were divided into a control group (Western medicine) and an observation group (one of four integrated Chinese and Western medicines). RESULTS 5 eligible publications were identified. A total of 598 cases were included in the study, and the results showed that the four types of integrated Chinese and Western medicines (symptomatic and supportive care with Qingfei Touxie Fuzheng, Lianhua Qingke, and Xuebijing) were significantly superior (P &lt;0.05) to symptomatic and supportive care alone, except for symptomatic and supportive care with Lianhua Qingwen. The combination of symptomatic and supportive care with Lianhua Qingke had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking (SUCRA) curve of 85.7. CONCLUSIONS A combination of symptomatic and supportive care with Lianhua Qingke is the best option among the four integrated Chinese and Western medicines considered for the treatment of COVID-19. RESUMO OBJETIVO Vários medicamentos chineses e ocidentais integrados podem ser benéficos para o tratamento da COVID-19. O objetivo deste estudo é avaliar a eficácia da tomografia computadorizada (TC) de pulmão de quatro medicamentos chineses e ocidentais integrados para o tratamento da COVID-19 usando uma meta-análise em rede (NMA). MÉTODOS Vários bancos de dados foram consultados para encontrar ensaios clínicos randomizados de quatro tipos diferentes de medicamentos chineses e ocidentais integrados para o tratamento da COVID-19. A NMA foi realizada nos dados usando o software Stata (13.0). O odds ratio (OR) foi calculado. Os estudos incluídos neste artigo foram divididos em um grupo de controle (medicina ocidental) e um grupo de observação (um dos quatro medicamentos chineses e ocidentais integrados). RESULTADOS 5 publicações elegíveis foram identificadas. Um total de 598 casos foram incluídos no estudo, e os resultados mostraram que os quatro tipos de medicamentos chineses e ocidentais integrados (tratamento sintomático e de suporte com Qingfei Touxie Fuzheng, Lianhua Qingke e Xuebijing) foram significativamente superiores (P &lt;0,05) a somente cuidados sintomáticos e de suporte, exceto cuidados sintomáticos e de suporte com Lianhua Qingwen. A combinação de cuidados sintomáticos e de suporte com Lianhua Qingke teve a maior probabilidade de ser a intervenção clinicamente mais eficaz, com uma superfície abaixo da curva de classificação cumulativa (SUCRA) de 85,7. CONCLUSÕES Uma combinação de tratamento sintomático e de suporte com Lianhua Qingke é a melhor opção entre os quatro medicamentos integrados chineses e ocidentais considerados para o tratamento de COVID-19.

Chinese Residents' Perceptions of COVID-19 During the Pandemic: Online Cross-sectional Survey Study.

BACKGROUND: COVID-19 has posed a global threat due to substantial morbidity and mortality, and health education strategies need to be adjusted accordingly to prevent a possible epidemic rebound. OBJECTIVE: This study aimed to evaluate the perceptions of COVID-19 among individuals coming to, returning to, or living in Jiangsu Province, China, and determine the impact of the pandemic on the perceptions of the public. METHODS: In this study, an online questionnaire was distributed to participants between February 15 and April 21, 2020. The questionnaire comprised items on personal information (eg, sex, age, educational level, and occupation); protection knowledge, skills, and behaviors related to COVID-19; access to COVID-19-related information; and current information needs. Factors influencing the knowledge score, skill score, behavior score, and total score for COVID-19 were evaluated using univariate and multivariate analyses. The time-varying reproduction number (Rt) and its 95% credible interval were calculated and compared with the daily participation number and protection scores. RESULTS: In total, 52,066 participants were included in the study; their average knowledge score, skill score, behavior score, and total score were 25.58 (SD 4.22), 24.05 (SD 4.02), 31.51 (SD 2.84), and 90.02 (SD 8.87), respectively, and 65.91% (34,315/52,066) had a total protection score above 90 points. For the knowledge and skill sections, correct rates of answers to questions on medical observation days, infectiousness of asymptomatic individuals, cough or sneeze treatment, and precautions were higher than 95%, while those of questions on initial symptoms (32,286/52,066, 62.01%), transmission routes (37,134/52,066, 71.32%), selection of disinfection products (37,390/52,066, 71.81%), and measures of home quarantine (40,037/52,066, 76.90%) were relatively low. For the actual behavior section, 97.93% (50,989/52,066) of participants could wear masks properly when going out. However, 19.76% (10,290/52,066) could not disinfect their homes each week, and 18.42% (9589/52,066) could not distinguish differences in initial symptoms between the common cold and COVID-19. The regression analyses showed that the knowledge score, skill score, behavior score, and total score were influenced by sex, age, educational level, occupation, and place of residence at different degrees (P<.001). The government, television shows, and news outlets were the main sources of protection knowledge, and the information released by the government and authoritative medical experts was considered the most reliable. The current information needs included the latest epidemic developments, disease treatment progress, and daily protection knowledge. The Rt in the Jiangsu Province and mainland China dropped below 1, while the global Rt remained at around 1. The maximal information coefficients ranged from 0.76 to 1.00, which indicated that the public's perceptions were significantly associated with the epidemic. CONCLUSIONS: A high proportion of the participants had sufficient COVID-19 protection knowledge and skills and were able to avoid risky behaviors. Thus, it is necessary to apply different health education measures tailored to work and study resumption for specific populations to improve their self-protection and, ultimately, to prevent a possible rebound of COVID-19.

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.

Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lungs from donors of ~30 weeks gestation,~3 years and ~30 years. We mapped candidate cis-regulatory elements (cCREs) and linked them to putative target genes. We identified distal cCREs with age-increased activity linked to SARS-CoV-2 host entry gene TMPRSS2 in alveolar type 2 cells, which had immune regulatory signatures and harbored variants associated with respiratory traits. At the 3p21.31 COVID-19 risk locus, a candidate variant overlapped a distal cCRE linked to SLC6A20, a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2. Our findings provide insight into regulatory logic underlying genes implicated in COVID-19 in individual lung cell types across age. More broadly, these datasets will facilitate interpretation of risk loci for lung diseases.

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID-19 pneumonia: A pilot study.

OBJECTIVES: We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in patients with severe and critically severe coronavirus disease-2019 (COVID-19). METHODS: We conducted a small sample, single arm, pilot trial. In addition to standard therapy, we performed four rounds of transplantation of UC-MSCs in sixteen patients with severe and critically severe COVID-19. We recorded adverse events from enrolment to Day 28. We evaluated the oxygenation index, inflammatory biomarkers, radiological presentations of the disease and lymphocyte subsets count on the 7th day (D7 ± 1 day), the 14th day (D14 ± 1 day) and the 28th day (D28 ± 3 days). RESULTS: There were no infusion-related or allergic reactions. The oxygenation index was improved after transplantation. The mortality of enrolled patients was 6.25%, whereas the historical mortality rate was 45.4%. The level of cytokines estimated varied in the normal range, the radiological presentations (ground glass opacity) were improved and the lymphocyte count and lymphocyte subsets (CD4+ T cells, CD8+ T cells and NK cells) count showed recovery after transplantation. CONCLUSIONS: Intravenous transplantation of UC-MSCs was safe and feasible for treatment of patients with severe and critically severe COVID-19 pneumonia.