Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

The impact of positive reinforcement on teamwork climate, resiliency, and burnout during the COVID-19 pandemic: The TEAM-ICU (Transforming Employee Attitudes via Messaging strengthens Interconnection, Communication, and Unity) pilot study.

Burnout is an internationally recognized occupational phenomenon that negatively impacts the healthcare workforce and its recipients. The aim of this pilot study was to test whether positive reinforcement and integrating a language of support among co-workers can enhance resiliency, facilitate psychological wellness, and encourage hope. This embedded mixed methods prospective, behavioral, interventional study evaluated the effects of positive feedback on wellness among intensive care unit clinicians during the COVID-19 pandemic in a single center, quaternary care medical center. The deliberate positive feedback paradigm has the potential to augment resiliency and improve attitudes toward a teamwork climate. The routine use of deliberate positivity may represent a scalable, low-cost initiative to enhance wellness in a healthcare organization.

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.

The association between the community SARS exposure and allostatic load among Chinese older adults.

OBJECTIVES: Previous studies have found that severe acute respiratory syndrome (SARS) was associated with the physical and psychological stress of those infected. However, research is sparse regarding the long-term health consequence of community SARS exposure for older adults. METHODS: Using data from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS), we estimated multilevel regression models of allostatic load (AL) in the years after the SARS epidemic among 7735 respondents. Interaction terms between SARS epidemic exposure and social participation or community environment were included to examine potential effects. RESULTS: We found that community SARS exposure was associated with greater AL for those who had no social participation. Among those who were in worse community environment, community SARS exposure was strongly related to elevated load in the cardiovascular system. However, for those had social participation and lived in better community environment, community SARS exposure manifested no association with AL years later. Active social participation and better community environment could offset the negative association between SARS exposure and AL. CONCLUSIONS: Taken together, these findings helped determine the positive direction of future social efforts and policy decisions to guide the global recovery from the devastating COVID-19 pandemic.

A high-specificity flap probe-based isothermal nucleic acid amplification method based on recombinant FEN1-Bst DNA polymerase.

The COVID-19 pandemic has unfortunately demonstrated how easily infectious diseases can spread and harm human life and society. As of writing, pandemic has now been on-going for more than one year. There is an urgent need for new nucleic acid-based methods that can be used to diagnose pathogens early, quickly, and accurately to effectively impede the spread of infections and gain control of epidemics. We developed a flap probe-based isothermal nucleic acid amplification method that is triggered by recombinant FEN1-Bst DNA polymerase, which-through enzymatic engineering-has both DNA synthesis, strand displacement and cleavage functions. This novel method offers a simpler and more specific probe-primer pair than those of other isothermal amplifications. We tested the method's ability to detect SARS-CoV-2 (both ORF1ab and N genes), rotavirus, and Chlamydia trachomatis. The limits of detection were 10 copies/µL for rotavirus, C. trachomatis, and SARS-CoV-2 N gene, and 100 copies/µL for SARS-CoV-2 ORF1ab gene. There were no cross-reactions among 11 other common pathogens with characteristics similar to those of the test target, and the method showed 100% sensitivity and 100% specificity in clinical comparisons with RT-PCR testing. In addition to real-time detection, the endpoint could be displayed under a transilluminator, which is a convenient reporting method for point-of-care test settings. Therefore, this novel nucleic acid senor has great potential for use in clinical diagnostics, epidemic prevention, and epidemic control.

Efficient Microfluidic-Based Air Sampling/Monitoring Platform for Detection of Aerosol SARS-CoV-2 On-site.

Airborne pathogens have been considered as highly infectious and transmittable between humans. With the pandemic outbreak of the coronavirus disease 2019 (COVID-19), an on-site diagnostic system-integrated airborne pathogen-monitoring machine is recommended by experts for preventing and controlling the early stage ß-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread. In this work, a small-volume rotating microfluidic fluorescence chip-integrated aerosol SARS-CoV-2 sampling system was constructed to satisfy the demand for rapid on-site sample collection and detection of SARS-CoV-2. The rotating microfluidic fluorescence system with small volume has very high sensitivity in the detection of SARS-CoV-2 (detection limit of 10 copies/µL with the shortest Ct value of 15 min), which is comparable to reverse transcription polymerase chain reaction (RT-PCR). The precision variation coefficients within/between batches are very low [coefficient of variation (CV) % ≤ 5.0%]. Our work has passed the comprehensive inspection of the microfluidic chip performance by the Shanghai Medical Device Testing Institute [National Medical Inspection (Design) no. 4408] and successfully tested 115 clinical samples. The integrated system exhibits 100% specificity, high sensitivity (10 copies/µL), and good precision (CV % ≤ 5.0%) in the rapid detection of SARS-CoV-2, thus realizing rapid monitoring and diagnostics of SARS-CoV-2 nucleic acid on-site.

Waitlisted Transplant Candidates' Attitudes and Concerns Toward Transplantation During COVID-19.

BACKGROUND In solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, coronavirus disease 2019 (COVID-19) can contribute to a severe clinical course and an increased risk of death. Thus, patients awaiting a SOT or HSCT face the dilemma of choosing between a life-saving treatment that presents a significant threat of COVID-19 and the risk of waitlist dropout, progression of disease, or mortality. The lack of established literature on COVID-19 complicates the issue as patients, particularly those with inadequate health literacy, may not have the resources needed to navigate these decisions. MATERIAL AND METHODS We conducted a standardized phone survey of patients awaiting SOT or HSCT to assess the prevalence of inadequate health literacy and attitudes toward transplant during the COVID-19 pandemic. RESULTS Seventy-one patients completed the survey, with a response rate of 84.5%. Regardless of health literacy, most waitlisted candidates recognized that the current pandemic is a serious situation affecting their care and that COVID-19 poses a significant risk to their health. Despite the increased risks, most patients reported they would choose immediate transplantation if there was no foreseeable end to the pandemic, and especially if the medical urgency did not permit further delay. There were no differences in responses across the patient waitlist groups for heart, kidney, liver, and stem cell transplant. CONCLUSIONS These findings can help transplant centers decide how transplantation services should proceed during this pandemic and can be used to educate patients and guide discussions about informed consent for transplant during the COVID-19 pandemic.

Epidemiological Features of 105 Patients Infected with the COVID-19.

OBJECTIVE: To investigate and evaluate the clinical features of patients infected with the 2019 novel coronavirus (COVID-19) outside of Wuhan. METHODS: 105 patients admitted to our hospital with clinical- and laboratory-confirmed COVID-19 infection were studied. Data were collected from January 17, 2020 to March 5, 2020. RESULTS: 105 patients (57 male and 48 female) were confirmed to have COVID-19 infection. Among the 105 patients, 55 (52%) had made short trips to Wuhan during the two weeks before the onset of illness, and these were the first-generation confirmed cases. An exact date of close contact with someone in Wenzhou with confirmed or suspected COVID-19 infection from Wuhan (the second-generation confirmed cases) could be provided by 38 (36%) patients. Of the remaining patients, six (6%; the third-generation confirmed cases) were familial clusters of the second-generation confirmed cases, three (3%) had no definite epidemiological features, and 16 (15%) were from the same location as for the case report. CONCLUSION: Due to the infectiousness of COVID-19, patients with infections should be diagnosed and treated as early as possible after developing fever symptoms or showing other clinical characteristics or imaging features. With respect to high-risk cases, we must focus on any complications that arise and take effective measures to treat them immediately. This will significantly improve the prognosis of patients with severe infections.

Residual SARS-CoV-2 viral antigens detected in gastrointestinal and hepatic tissues from two recovered COVID-19 patients (preprint)

Residual SARS-CoV-2 RNA has been detected in stool samples and gastrointestinal tissues during the convalescence phase of COVID-19 infection. This raises concern for persistence of SARS-CoV-2 virus particles and faecal-oral transmissibility in recovered COVID-19 patients. Using multiplex immunohistochemistry, we unexpectedly detected SARS-CoV-2 viral antigens in intestinal and liver tissues, in surgical samples obtained from two patients who recovered from COVID-19. We further validated the presence of virus by RT-PCR and flow cytometry to detect SARS-CoV-2-specific immunity in the tissues. These findings might have important implications in terms of disease management and public health policy regarding transmission of COVID-19 via faecal-oral and iatrogenic routes during the convalescence phase.

Rapid Differential Diagnosis of Seven Human Respiratory Coronaviruses Based on Centrifugal Microfluidic Nucleic Acid Assay.

With the global outbreak of the coronavirus disease 2019 (COVID-19), the highly infective, highly pathogenic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted great attention. Currently, a method to simultaneously diagnose the seven known types human coronaviruses remains lacking and is urgently needed. In this work, we successfully developed a portable microfluidic system for the rapid, accurate, and simultaneous detection of SARS-CoV, middle east respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2, and four other human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. The disk-like microfluidic platform integrated with loop-mediated isothermal amplification provides highly accurate, sensitive, and specific results with a wide linear range within 40 min. The diagnostic tool achieved 100% consistency with the "gold standard" polymerase chain reaction in detecting 54 real clinical samples. The integrated system, with its simplicity, is urgently needed for the diagnosis of SARS-CoV-2 during the COVID-19 pandemic.

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

CSCO ablation expert workshop report: Recommendations for the management of tumor ablation during the coronavirus disease 2019 epidemic.

The coronavirus disease 2019 (COVID-19) has become a global pandemic since its outbreak in December 2019, which posed a threat to the safety and well-being of people on a global scale. Cancer patients are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and their critical morbidity and case fatality rates are high. The ablation expert committee of the Chinese Society of Clinical Oncology compiled corresponding expert recommendations. These recommendations summarize the preventive measures and management of tumor ablation treatment in medical institutions, including outpatient clinics, oncology wards, ablation operation room, and postablation follow-ups in accordance with the guidelines and protocols imposed by the National Health Commission of the People's Republic of China and the experience in management and prevention according to various hospitals. This consensus aims to reduce and prevent the spread of SARS-CoV-2 and its cross-infection between cancer patients in hospitals and provide regulatory advice and guidelines for medical personnel.