PanDa Game: Optimized Privacy-Preserving Publishing of Individual-Level Pandemic Data Based on a Game Theoretic Model.

Sharing individual-level pandemic data is essential for accelerating the understanding of a disease. For example, COVID-19 data have been widely collected to support public health surveillance and research. In the United States, these data are typically de-identified before publication to protect the privacy of the corresponding individuals. However, current data publishing approaches for this type of data, such as those adopted by the U.S. Centers for Disease Control and Prevention (CDC), have not flexed over time to account for the dynamic nature of infection rates. Thus, the policies generated by these strategies have the potential to both raise privacy risks or overprotect the data and impair the data utility (or usability). To optimize the tradeoff between privacy risk and data utility, we introduce a game theoretic model that adaptively generates policies for the publication of individual-level COVID-19 data according to infection dynamics. We model the data publishing process as a two-player Stackelberg game between a data publisher and a data recipient and then search for the best strategy for the publisher. In this game, we consider 1) the average performance of predicting future case counts, and 2) the mutual information between the original data and the released data. We use COVID-19 case data from Vanderbilt University Medical Center from March 2020 to December 2021 to demonstrate the effectiveness of the new model. The results indicate that the game theoretic model outperforms all state-of-the-art baseline approaches, including those adopted by CDC, while maintaining low privacy risk. We further perform an extensive sensitivity analyses to show that our findings are robust to order-of-magnitude parameter fluctuations.

Rapid detection of mpox virus using recombinase aided amplification assay

A recent, unprecedented outbreak of human mpox virus infection has led to cases in non-African nations, and the number of confirmed or suspected cases outside of Africa has exceeded 1,000 within 5 weeks. Mpox may pose a double threat to public health in the context of the ongoing COVID-19 pandemic. It is difficult to distinguish mpox virus infection from other diseases in the early stages, and patients are contagious from the onset of nonspecific symptoms;therefore, it is crucial to develop rapid and specific diagnostic methods. The diagnosis of mpox relies on real-time polymerase chain reaction, a time-consuming method that requires a highly sophisticated thermal cycler, which makes it unsuitable for widespread use in underdeveloped areas, where the outbreak is still severe. In this study, we developed a recombinase-aided amplification (RAA) assay that can detect mpox virus within 5–10 minutes. The conserved regions of the A27L gene and F3L gene were selected as targets, as they amplify well from different mpox virus clades with no cross-reaction from other pathogens. The sensitivity of this RAA assay is 10 copies/reaction for the A27L gene and 102 copies/reaction for the F3L gene. When applied to simulated clinical samples, both targets showed 100% specificity, and the detection limits were consistent with the sensitivity results. Moreover, through clinical blinded sample detection, RAA exhibits the same detection power as RT-PCR. In summary, the RAA mpox assay described here exhibits rapid detection, high sensitivity and specificity, and low operational difficulty, making it suitable for mpox virus detection in less developed countries and regions.

Rapid detection of mpox virus using recombinase aided amplification assay.

A recent, unprecedented outbreak of human mpox virus infection has led to cases in non-African nations, and the number of confirmed or suspected cases outside of Africa has exceeded 1,000 within 5 weeks. Mpox may pose a double threat to public health in the context of the ongoing COVID-19 pandemic. It is difficult to distinguish mpox virus infection from other diseases in the early stages, and patients are contagious from the onset of nonspecific symptoms; therefore, it is crucial to develop rapid and specific diagnostic methods. The diagnosis of mpox relies on real-time polymerase chain reaction, a time-consuming method that requires a highly sophisticated thermal cycler, which makes it unsuitable for widespread use in underdeveloped areas, where the outbreak is still severe. In this study, we developed a recombinase-aided amplification (RAA) assay that can detect mpox virus within 5-10 minutes. The conserved regions of the A27L gene and F3L gene were selected as targets, as they amplify well from different mpox virus clades with no cross-reaction from other pathogens. The sensitivity of this RAA assay is 10 copies/reaction for the A27L gene and 102 copies/reaction for the F3L gene. When applied to simulated clinical samples, both targets showed 100% specificity, and the detection limits were consistent with the sensitivity results. Moreover, through clinical blinded sample detection, RAA exhibits the same detection power as RT-PCR. In summary, the RAA mpox assay described here exhibits rapid detection, high sensitivity and specificity, and low operational difficulty, making it suitable for mpox virus detection in less developed countries and regions.

Drivers of High Concentrations of Secondary Organic Aerosols in Northern China during the COVID-19 Lockdowns.

During the COVID-19 lockdown in early 2020, observations in Beijing indicate that secondary organic aerosol (SOA) concentrations increased despite substantial emission reduction, but the reasons are not fully explained. Here, we integrate the two-dimensional volatility basis set into a state-of-the-art chemical transport model, which unprecedentedly reproduces organic aerosol (OA) components resolved by the positive matrix factorization based on aerosol mass spectrometer observations. The model shows that, for Beijing, the emission reduction during the lockdown lowered primary organic aerosol (POA)/SOA concentrations by 50%/18%, while deteriorated meteorological conditions increased them by 30%/119%, resulting in a net decrease in the POA concentration and a net increase in the SOA concentration. Emission reduction and meteorological changes both led to an increased OH concentration, which accounts for their distinct effects on POA and SOA. SOA from anthropogenic volatile organic compounds and organics with lower volatility contributed 28 and 62%, respectively, to the net SOA increase. Different from Beijing, the SOA concentration decreased in southern Hebei during the lockdown because of more favorable meteorology. Our findings confirm the effectiveness of organic emission reductions and meanwhile reveal the challenge in controlling SOA pollution that calls for large organic precursor emission reductions to rival the adverse impact of OH increase.

Examining Rural and Urban Sentiment Difference in COVID-19-Related Topics on Twitter: Word Embedding-Based Retrospective Study.

BACKGROUND: By the end of 2022, more than 100 million people were infected with COVID-19 in the United States, and the cumulative death rate in rural areas (383.5/100,000) was much higher than in urban areas (280.1/100,000). As the pandemic spread, people used social media platforms to express their opinions and concerns about COVID-19-related topics. OBJECTIVE: This study aimed to (1) identify the primary COVID-19-related topics in the contiguous United States communicated over Twitter and (2) compare the sentiments urban and rural users expressed about these topics. METHODS: We collected tweets containing geolocation data from May 2020 to January 2022 in the contiguous United States. We relied on the tweets' geolocations to determine if their authors were in an urban or rural setting. We trained multiple word2vec models with several corpora of tweets based on geospatial and timing information. Using a word2vec model built on all tweets, we identified hashtags relevant to COVID-19 and performed hashtag clustering to obtain related topics. We then ran an inference analysis for urban and rural sentiments with respect to the topics based on the similarity between topic hashtags and opinion adjectives in the corresponding urban and rural word2vec models. Finally, we analyzed the temporal trend in sentiments using monthly word2vec models. RESULTS: We created a corpus of 407 million tweets, 350 million (86%) of which were posted by users in urban areas, while 18 million (4.4%) were posted by users in rural areas. There were 2666 hashtags related to COVID-19, which clustered into 20 topics. Rural users expressed stronger negative sentiments than urban users about COVID-19 prevention strategies and vaccination (P<.001). Moreover, there was a clear political divide in the perception of politicians by urban and rural users; these users communicated stronger negative sentiments about Republican and Democratic politicians, respectively (P<.001). Regarding misinformation and conspiracy theories, urban users exhibited stronger negative sentiments about the "covidiots" and "China virus" topics, while rural users exhibited stronger negative sentiments about the "Dr. Fauci" and "plandemic" topics. Finally, we observed that urban users' sentiments about the economy appeared to transition from negative to positive in late 2021, which was in line with the US economic recovery. CONCLUSIONS: This study demonstrates there is a statistically significant difference in the sentiments of urban and rural Twitter users regarding a wide range of COVID-19-related topics. This suggests that social media can be relied upon to monitor public sentiment during pandemics in disparate types of regions. This may assist in the geographically targeted deployment of epidemic prevention and management efforts.

The association between physical activity and mental health in medical postgraduates in China during COVID-19 pandemic.

Background: Chinese medical postgraduates (CMPs) are a special subpopulation that has a great risk of mental health due to high workload, and heavy academic and clinical pressure during the COVID-19 pandemic. Physical activity has been demonstrated to be positive for the mental health of human being. However, little is known about the risks to mental health among CMPs as well as the potential effects of physical activity on mental health in CMPs during the COVID-19 pandemic. Aims: In the present study, the aims are to (1) investigate the levels of PA and mental health that CMPs had; (2) to identify the potential factors that contribute to mental health among CMPs; (3) to explore the potential effects of PA on the mental health in CMPs. Methods: The survey was conducted online across 25 provinces of mainland China in 28 medical colleges or universities with structured questionnaires. Physical Activity Rating Scale-3 (PARS-3), Depression, Anxiety, Stress Scales (DASS-21), and General Self-Efficacy Scale (GSES) were employed to assess the levels of PA, Negative emotional states, and self-efficacy of the participants, respectively. Resilience was evaluated using Connor-Davidson Resilience Scale (CD-RISC). The chi-square and Wilcoxon rank-sum tests were used to compare inter-group differences in demographic data and mental health conditions. Spearman's rank correlation test and partial correlation analysis were used to assess associations between exercise scores and mental health. Results: We found some socio-demographic variables such as the location, education levels of parents and the levels of degrees they are training had potential effects on outcomes of mental health among 2,217 CMPs (P < 0.05); furthermore, we also found that PA was negatively correlated with the negative emotion (r = -0.045, P < 0.05) such as depression (r = -0.052, P < 0.05), anxiety and stress, (r = -0.051, P < 0.05) but positively correlated with the self-efficacy (r = 0.143, P < 0.001) and resilience (r = 0.192, P < 0.001) among Chinese postgraduate medical students. Conclusion: We concluded that for Chinese postgraduate medical students, taking part in physical activity would depress negative emotions such as depression, anxiety, and stress, but improve their self-efficacy and resilience, which will benefit them in completing their studies and training.

Development of a Loop-Mediated Isothermal Amplification Method for Rapid and Visual Detection of Monkeypox Virus.

Monkeypox virus (MPXV) is a human pathogenic virus that belongs to the genus Orthopoxvirus. In 2022, MPXV caused an unprecedented number of infections in many countries. As it is difficult to distinguish MPXV from other pathogens by its symptoms in the early stage of infection, a rapid and reliable assay for MPXV detection is needed. In this study, we developed a loop-mediated isothermal amplification (LAMP) assay for the specific detection of MPXV and evaluated its application in simulated clinical samples. The A27L-1 and F3L-1 primer sets were identified as the optimal primers, and 63°C was the most appropriate reaction temperature for sequence amplification. The detection limits of the LAMP assay using primer sets A27L-1 and F3L-1 were both 20 copies/reaction mixture, which were >100-fold higher in terms of sensitivity, compared with conventional PCR. The LAMP assay findings were negative for all 21 non-MPXV pathogens, confirming the high specificity of our assay. All three types of simulated clinical samples were clearly identified by our LAMP assay, and the detection limits were consistent with the sensitivity results, indicating efficient clinical sample identification. Our rapid and reliable MPXV LAMP assay could be useful for MPXV detection and on-site diagnosis, especially in primary hospitals and rural areas. IMPORTANCE MPXV outbreaks rapidly grew in the first half of 2022, and this virus has been recognized as an increasing public health threat, particularly in the context of the COVID-19 pandemic. Thus, developing reliable and fast detection methods for MPXV is necessary.

Dynamically adjusting case reporting policy to maximize privacy and public health utility in the face of a pandemic.

OBJECTIVE: Supporting public health research and the public's situational awareness during a pandemic requires continuous dissemination of infectious disease surveillance data. Legislation, such as the Health Insurance Portability and Accountability Act of 1996 and recent state-level regulations, permits sharing deidentified person-level data; however, current deidentification approaches are limited. Namely, they are inefficient, relying on retrospective disclosure risk assessments, and do not flex with changes in infection rates or population demographics over time. In this paper, we introduce a framework to dynamically adapt deidentification for near-real time sharing of person-level surveillance data. MATERIALS AND METHODS: The framework leverages a simulation mechanism, capable of application at any geographic level, to forecast the reidentification risk of sharing the data under a wide range of generalization policies. The estimates inform weekly, prospective policy selection to maintain the proportion of records corresponding to a group size less than 11 (PK11) at or below 0.1. Fixing the policy at the start of each week facilitates timely dataset updates and supports sharing granular date information. We use August 2020 through October 2021 case data from Johns Hopkins University and the Centers for Disease Control and Prevention to demonstrate the framework's effectiveness in maintaining the PK11 threshold of 0.01. RESULTS: When sharing COVID-19 county-level case data across all US counties, the framework's approach meets the threshold for 96.2% of daily data releases, while a policy based on current deidentification techniques meets the threshold for 32.3%. CONCLUSION: Periodically adapting the data publication policies preserves privacy while enhancing public health utility through timely updates and sharing epidemiologically critical features.

Evolution of organic carbon during COVID-19 lockdown period: Possible contribution of nocturnal chemistry.

Carbonaceous aerosol is one of the main components of atmospheric particulate matter, which is of great significance due to its role in climate change, earth's radiation balance, visibility, and human health. In this work, carbonaceous aerosols were measured in Shijiazhuang and Beijing using the OC/EC analyzer from December 1, 2019 to March 15, 2020, which covered the Coronavirus Disease 2019 (COVID-19) pandemic. The observed results show that the gas-phase pollutants, such as NO, NO2, and aerosol-phase pollutants (Primary Organic Compounds, POC) from anthropogenic emissions, were significantly reduced during the lockdown period due to limited human activities in North China Plain (NCP). However, the atmospheric oxidation capacity (Ox/CO) shows a significantly increase during the lockdown period. Meanwhile, additional sources of nighttime Secondary Organic Carbon (SOC), Secondary Organic Aerosol (SOA), and babs, BrC(370 nm) are observed and ascribed to the nocturnal chemistry related to NO3 radical. The Potential Source Contribution Function (PSCF) analysis indicates that the southeast areas of the NCP region contributed more to the SOC during the lockdown period than the normal period. Our results highlight the importance of regional nocturnal chemistry in SOA formation.

Assessing Neonatal Intensive Care Unit Structures and Outcomes Before and During the COVID-19 Pandemic: Network Analysis Study.

BACKGROUND: Health care organizations (HCOs) adopt strategies (eg. physical distancing) to protect clinicians and patients in intensive care units (ICUs) during the COVID-19 pandemic. Many care activities physically performed before the COVID-19 pandemic have transitioned to virtual systems during the pandemic. These transitions can interfere with collaboration structures in the ICU, which may impact clinical outcomes. Understanding the differences can help HCOs identify challenges when transitioning physical collaboration to the virtual setting in the post-COVID-19 era. OBJECTIVE: This study aims to leverage network analysis to determine the changes in neonatal ICU (NICU) collaboration structures from the pre- to the intra-COVID-19 era. METHODS: In this retrospective study, we applied network analysis to the utilization of electronic health records (EHRs) of 712 critically ill neonates (pre-COVID-19, n=386; intra-COVID-19, n=326, excluding those with COVID-19) admitted to the NICU of Vanderbilt University Medical Center between September 1, 2019, and June 30, 2020, to assess collaboration between clinicians. We characterized pre-COVID-19 as the period of September-December 2019 and intra-COVID-19 as the period of March-June 2020. These 2 groups were compared using patients' clinical characteristics, including age, sex, race, length of stay (LOS), and discharge dispositions. We leveraged the clinicians' actions committed to the patients' EHRs to measure clinician-clinician connections. We characterized a collaboration relationship (tie) between 2 clinicians as actioning EHRs of the same patient within the same day. On defining collaboration relationship, we built pre- and intra-COVID-19 networks. We used 3 sociometric measurements, including eigenvector centrality, eccentricity, and betweenness, to quantify a clinician's leadership, collaboration difficulty, and broad skill sets in a network, respectively. We assessed the extent to which the eigenvector centrality, eccentricity, and betweenness of clinicians in the 2 networks are statistically different, using Mann-Whitney U tests (95% CI). RESULTS: Collaboration difficulty increased from the pre- to intra-COVID-19 periods (median eccentricity: 3 vs 4; P<.001). Nurses had reduced leadership (median eigenvector centrality: 0.183 vs 0.087; P<.001), and neonatologists with broader skill sets cared for more patients in the NICU structure during the pandemic (median betweenness centrality: 0.0001 vs 0.005; P<.001). The pre- and intra-COVID-19 patient groups shared similar distributions in sex (~0 difference), race (4% difference in White, and 3% difference in African American), LOS (interquartile range difference in 1.5 days), and discharge dispositions (~0 difference in home, 2% difference in expired, and 2% difference in others). There were no significant differences in the patient demographics and outcomes between the 2 groups. CONCLUSIONS: Management of NICU-admitted patients typically requires multidisciplinary care teams. Understanding collaboration structures can provide fine-grained evidence to potentially refine or optimize existing teamwork in the NICU.

Decreased inhibition of exosomal miRNAs on SARS-CoV-2 replication underlies poor outcomes in elderly people and diabetic patients.

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

Modeling the effect of reduced traffic due to COVID-19 measures on air quality using a chemical transport model: impacts on the Po Valley and the Swiss Plateau regions.

The spread of COVID-19 has posed serious challenges for the global communities. To reduce the circulation of the infection, governmental bodies have imposed different lockdown measures at various levels of complexity and duration. As a result, a substantial reduction in mobility might have important, yet unknown, implications for air quality. In this study, we applied the Comprehensive Air quality Model with eXtensions (CAMx) to investigate potential changes in air quality and its chemical composition over northern Italy and Switzerland during periods when lockdown measures were enforced. Our results indicated that lockdown measures reduced nitrogen dioxide (NO2) air concentrations by up to 46% and 25% in the Po Valley and Swiss Plateau regions, respectively, whereas fine particulate matter (PM2.5) air concentrations were reduced only by up to 10% and 6%. This highlights the importance of other emission categories other than traffic for the total PM2.5 levels. The analysis of the PM2.5 components indicated that elemental carbon (EC) and particulate nitrate (NO3 -) were the species most affected by the lockdown measures, whereas a mild increase in the secondary organic aerosol (SOA) concentrations occurred in the Po Valley, and specifically over the metropolitan area of Milan. Our results indicated that an increase in the oxidation capacity of the atmosphere, i.e. in the ˙OH and ˙NO3 radicals, was mainly responsible for the mild increase in SOA concentrations.

What can cerebrospinal fluid testing and brain autopsies tell us about viral neuroinvasion of SARS-CoV-2.

To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we analyzed the existing literature on viral neuroinvasion of SARS-CoV-2 in coronavirus disease 2019 (COVID-19) patients. To date, SARS-CoV-2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS-CoV-2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS-CoV-2 is rare in COVID-19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID-19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS-CoV-2 infection.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.

Collaboration Structures in COVID-19 Critical Care: Retrospective Network Analysis Study.

BACKGROUND: Few intensive care unit (ICU) staffing studies have examined the collaboration structures of health care workers (HCWs). Knowledge about how HCWs are connected to the care of critically ill patients with COVID-19 is important for characterizing the relationships among team structures, care quality, and patient safety. OBJECTIVE: We aimed to discover differences in the teamwork structures of COVID-19 critical care by comparing HCW collaborations in the management of critically ill patients with and without COVID-19. METHODS: In this retrospective study, we used network analysis methods to analyze the electronic health records (EHRs) of 76 critically ill patients (with COVID-19: n=38; without COVID-19: n=38) who were admitted to a large academic medical center, and to learn about HCW collaboration. We used the EHRs of adult patients who were admitted to the COVID-19 ICU at the Vanderbilt University Medical Center (Nashville, Tennessee, United States) between March 17, 2020, and May 31, 2020. We matched each patient according to age, gender, and their length of stay. Patients without COVID-19 were admitted to the medical ICU between December 1, 2019, and February 29, 2020. We used two sociometrics-eigencentrality and betweenness-to quantify HCWs' statuses in networks. Eigencentrality characterizes the degree to which an HCW is a core person in collaboration structures. Betweenness centrality refers to whether an HCW lies on the path of other HCWs who are not directly connected. This sociometric was used to characterize HCWs' broad skill sets. We measured patient staffing intensity in terms of the number of HCWs who interacted with patients' EHRs. We assessed the statistical differences in the core and betweenness statuses of HCWs and the patient staffing intensities of COVID-19 and non-COVID-19 critical care, by using Mann-Whitney U tests and reporting 95% CIs. RESULTS: HCWs in COVID-19 critical care were more likely to frequently work with each other (eigencentrality: median 0.096) than those in non-COVID-19 critical care (eigencentrality: median 0.057; P<.001). Internal medicine physicians in COVID-19 critical care had higher core statuses than those in non-COVID-19 critical care (P=.001). Nurse practitioners in COVID-19 care had higher betweenness statuses than those in non-COVID-19 care (P<.001). Compared to HCWs in non-COVID-19 settings, the EHRs of critically ill patients with COVID-19 were used by a larger number of internal medicine nurse practitioners (P<.001), cardiovascular nurses (P<.001), and surgical ICU nurses (P=.002) and a smaller number of resident physicians (P<.001). CONCLUSIONS: Network analysis methodologies and data on EHR use provide a novel method for learning about differences in collaboration structures between COVID-19 and non-COVID-19 critical care. Health care organizations can use this information to learn about the novel changes that the COVID-19 pandemic has imposed on collaboration structures in urgent care.

Neurological involvement in the respiratory manifestations of COVID-19 patients.

The peculiar features of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), are challenging the current biological knowledge. Early in Feb, 2020, we suggested that SARS-CoV-2 may possess neuroinvasive potential similar to that of many other coronaviruses. Since then, a variety of neurological manifestations have been associated with SARS-CoV-2 infection, which was supported in some patients with neuroimaging and/or cerebrospinal fluid tests. To date, at least 27 autopsy studies on the brains of COVID-19 patients can be retrieved through PubMed/MEDLINE, among which neuropathological alterations were observed in the brainstem in 78 of 134 examined patients, and SARS-CoV-2 nucleic acid and viral proteins were detected in the brainstem in 16/49 (32.7%) and 18/71 (25.3%) cases, respectively. To shed some light on the peculiar respiratory manifestations of COVID-19 patients, this review assessed the existing evidence about the neurogenic mechanism underlying the respiratory failure induced by SARS-CoV-2 infection. Acknowledging the neurological involvement has important guiding significance for the prevention, treatment, and prognosis of SARS-CoV-2 infection.

Hyperbaric oxygen therapy in an elderly critical coronavirus disease 2019 patient with endotracheal intubation: clinical effect analysis

Objective To sum up our experience of hyperbaric oxygen therapy (HBOT) in an elderly critical coronavirus disease 2019 (COVID-19) patient with endotracheal intubation, providing references for the application of HBOT in COVID-19 treatment. Methods and results The patient was 87 years old male and presented coma symptoms on Feb. 3, 2020. Chest computed tomography (CT) showed multiple small flake fuzzy shadows in both lungs. The nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar lavage fluid was positive on Feb.5 and the diagnosis of COVID-19 was confirmed. After symptomatic and supportive treatment, the patient's condition became stable gradually, and the tracheal intubation was removed on Feb. 22. However, the patient was intubated again on Feb. 24 because of loss of coughing and sputum expelling abilities, and the patient's condition was judged to be critical. On Feb. 29, the patient received HBOT for the first time, and medical staff entered the hyperbaric oxygen cabin through the special channel. After HBOT for four times, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) of the patient tended to be stable, carbon dioxide retention was alleviated, liver and kidney function improved, and coagulation function recovered. On Mar. 6, SARS-CoV-2 immunoglobulin (Ig) test showed that SARS-CoV-2 IgM was negative and SARS-CoV-2 IgG was positive. The patient was then transferred to general wards. Conclusion HBOT can alleviate CO2 retention in critical COVID-19 patients, and has a positive effect on reducing hypoxia and protecting important organs. The HBOT infection control procedure is feasible, and the safety of medical staff can be guaranteed by reasonable design.

Efficacy analysis of hyperbaric oxygen therapy in the treatment of severe coronavirus disease 2019 patients

Objective To explore the potential mechanisms underlying the prominent efficiency of hyperbaric oxygen therapy (HBOT) in the treatment of severe coronavirus disease 2019 (COVID-19) patients. Methods Five COVID-19 patients, aged from 24 to 69 years old, received HBOT after routine therapies failed to stop the deterioration and progressive hypoxemia in General Hospital of the Yangtze River Shipping. The procedure of HBOT was as follows: compressed to 2.0 ATA (0.1 MPa gauge pressure, patient 1) or 1.6 ATA (0.06 MPa gauge pressure, patient 2-5) at a constant rate for 15 min, maintained for 90 min (first treatment) or 60 min (subsequent treatment), then decompressed to normal pressure for 20 min, once a day;the patients inhaled oxygen with the mask of Built-in-Breathing System continuously;and HBOT was ended when the daily mean pulse oxygen saturation (SpO2) in wards was above 95% for two days. The symptoms, respiratory rate (RR), SpO2, arterial blood gas analysis, blood routine, coagulation function, high-sensitivity C-reactive protein (hs-CRP) and chest computed tomography (CT) were collected. Paired t test was used to compare each index before and after treatment. Results After the first HBOT, the symptoms and signs of the five patients began to improve. Supine breathlessness disappeared after HBOT for four times, and digestive tract symptoms completely disappeared and only mild chest pain and breathlessness at rest and in motion remained after HBOT for five times. After finishing HBOT, the RR of the patients was significanlty lower than that before HBOT ([20.80±2.28] min-1 vs [27.20±5.40] min-1, P<0.05). After finishing HBOT, daily SpO2 in wards was increased day by day, and the daily mean SpO2 recovered to more than 95% after the first, second, third, third and sixth HBOT in the five patients, respectively. After the first HBOT decompression, SpO2 was (93.60±0.07)%, which was signficantly higher than that before HBOT ([73.20±6.42] %) (P<0.05). SpO2 values before compression of the second and third HBOT were signficantly higher than that before the first HBOT (both P<0.05). There was no significant difference in the SpO2 immediately before and after the third HBOT (P>0.05). Before HBOT, the arterial partial pressure of carbon dioxide (PaCO2) of the patients was (31.48±3.40) mmHg (1 mmHg=0.133 kPa), which was lower than the normal range (35-45 mmHg). After finishing HBOT, arterial partial pressure of oxygen ([130.20±18.58] mmHg), arterial oxygen saturation ([98.40±0.55]%), lymphocyte proportion (0.207 8±0.074 2) and lymphocyte count ([1.09±0.24]×109/L) were significantly higher than those before HBOT ([61.60±15.24] mmHg, [73.20±6.43]%, 0.094 6±0.062 1, and [0.61± 0.35]×109/L), while the levels of fibrinogen ([2.97±0.27] g/L) and hs-CRP ([7.76±6.95] mg/L) were significantly lower than those before HBOT ([4.45±0.94] g/L and [30.36±1.27] mg/L) (all P<0.05). The levels of lacttic acid and D-dimer were decreased after HBOT versus before HBOT ([1.13±0.10] mmol/L vs [2.16±1.71] mmol/L, [0.42±0.13] mg/L vs [1.84±1.29] mg/L), but the differences were not significant (both P>0.05). All the five patients had typical lung CT imaging changes of severe COVID-19 before HBOT, which were improved after HBOT. Conclusion Systemic hypoxia induced by persistent hypoxemia may be the main reason for the deterioration of severe COVID-19. The respiratory dysfunction of COVID-19 is mainly alveolar gas exchange dysfunction. HBOT may be the best way to correct the progressive hypoxemia which can not be controlled by atmospheric oxygen supply in severe COVID-19 patients. HBOT can provide enough oxygen supply for the continuous hypoxia tissues, and is beneficial to the recovery of immune function, circulatory function and stress level, so as to improve the condition of patients.

The possible impairment of respiratory-related neural loops may be associated with the silent pneumonia induced by SARS-CoV-2.

As compared to many other viral pulmonary infections, there existed several peculiar manifestations in the COVID-19 patients, including the "silence" of pneumonia in both mild and severe cases and a long intensive care unit stay for those requiring invasive mechanical ventilation. Similar silent pneumonia has been documented in the infectioninduced by H5N1 influenza virus HK483 and was found to result from the direct attack of the virus on the bronchopulmonary C-fibers at the early stage and the final infection in the brainstem at the late stage. The long stay of critical patients in the intensive care unit is possibly due to the depression of central respiratory drive, which resulted in the failure to wean from the mechanic ventilation. Carotid and aortic bodies and bronchopulmonary C-fibers are two key peripheral components responsible for the chemosensitive responses in the respiratory system, while triggering respiratory reflexes depends predominantly on the putative chemosensitive neurons located in the pontomedullary nuclei. In view of the findings for the H5N1 influenza virus, the silence of pneumonia induced by SARS-CoV-2 may be due to the possible impairment of peripheral chemosensitive reflexes as well as the damage to the respiratory-related central neurons.

Reverse-Transcription Recombinase-Aided Amplification Assay for Rapid Detection of the 2019 Novel Coronavirus (SARS-CoV-2).

A novel coronavirus (SARS-CoV-2) was recently identified in patients with acute respiratory disease and spread quickly worldwide. A specific and rapid diagnostic method is important for early identification. The reverse-transcription recombinase-aided amplification (RT-RAA) assay is a rapid detection method for several pathogens. Assays were performed within 5-15 min as a one-step single tube reaction at 39 °C. In this study, we established two RT-RAA assays for the S and orf1ab gene of SARS-CoV-2 using clinical specimens for validation. The analytical sensitivity of the RT-RAA assay was 10 copies for the S and one copy for the orf1ab gene per reaction. Cross-reactions were not observed with any of the other respiratory pathogens. A 100% agreement between the RT-RAA and real-time PCR assays was accomplished after testing 120 respiratory specimens. These results demonstrate that the proposed RT-RAA assay will be beneficial as it is a faster, more sensitive, and more specific tool for the detection of SARS-CoV-2.