Smart healthcare: A prospective future medical approach for COVID-19.

COVID-19 has greatly affected human life for over 3 years. In this review, we focus on smart healthcare solutions that address major requirements for coping with the COVID-19 pandemic, including (1) the continuous monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), (2) patient stratification with distinct short-term outcomes (e.g. mild or severe diseases) and long-term outcomes (e.g. long COVID), and (3) adherence to medication and treatments for patients with COVID-19. Smart healthcare often utilizes medical artificial intelligence (AI) and cloud computing and integrates cutting-edge biological and optoelectronic techniques. These are valuable technologies for addressing the unmet needs in the management of COVID. By leveraging deep/machine learning (DL/ML) capabilities and big data, medical AI can perform precise prognosis predictions and provide reliable suggestions for physicians' decision-making. Through the assistance of the Internet of Medical Things (IoMT), which encompasses wearable devices, smartphone apps, Internet-based drug delivery systems, and telemedicine technologies, the status of mild cases can be continuously monitored and medications provided at home without the need for hospital care. In cases that develop into severe cases, emergency feedback can be provided through the hospital for rapid treatment. Smart healthcare can possibly prevent the development of severe COVID-19 cases and therefore lower the burden on intensive care units.

Tunable MEMS-Based Terahertz Metamaterial for Pressure Sensing Application.

In this study, a tunable terahertz (THz) metamaterial using the micro-electro-mechanical system (MEMS) technique is proposed to demonstrate pressure sensing application. This MEMS-based tunable metamaterial (MTM) structure is composed of gold (Au) split-ring resonators (SRRs) on patterned silicon (Si) substrate with through Si via (TSV). SRR is designed as a cantilever on the TSV structure. When the airflow passes through the TSV from bottom to up and then bends the SRR cantilever, the SRR cantilever will bend upward. The electromagnetic responses of MTM show the tunability and polarization-dependent characteristics by bending the SRR cantilever. The resonances can both be blue-shifted from 0.721 THz to 0.796 THz with a tuning range of 0.075 THz in transverse magnetic (TM) mode and from 0.805 THz to 0.945 THz with a tuning range of 0.140 THz in transverse electric (TE) mode by changing the angle of SRR cantilever from 10° to 45°. These results provide the potential applications and possibilities of MTM design for use in pressure and flow rate sensors.

Stemming the Rise of Antibiotic Use for Community-Acquired Acute Respiratory Infections during COVID-19 Pandemic.

At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify "high yield" interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6-8) vs. 6 (3-8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to "complete the course" (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber's practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance.

Portable FRET-Based Biosensor Device for On-Site Lead Detection.

Most methods for measuring environmental lead (Pb) content are time consuming, expensive, hazardous, and restricted to specific analytical systems. To provide a facile, safe tool to detect Pb, we created pMet-lead, a portable fluorescence resonance energy transfer (FRET)-based Pb-biosensor. The pMet-lead device comprises a 3D-printed frame housing a 405-nm laser diode-an excitation source for fluorescence emission images (YFP and CFP)-accompanied by optical filters, a customized sample holder with a Met-lead 1.44 M1 (the most recent version)-embedded biochip, and an optical lens aligned for smartphone compatibility. Measuring the emission ratios (Y/C) of the FRET components enabled Pb detection with a dynamic range of nearly 2 (1.96), a pMet-lead/Pb dissociation constant (Kd) 45.62 nM, and a limit of detection 24 nM (0.474 µg/dL, 4.74 ppb). To mitigate earlier problems with a lack of selectivity for Pb vs. zinc, we preincubated samples with tricine, a low-affinity zinc chelator. We validated the pMet-lead measurements of the characterized laboratory samples and unknown samples from six regions in Taiwan by inductively coupled plasma mass spectrometry (ICP-MS). Notably, two unknown samples had Y/C ratios significantly higher than that of the control (3.48 ± 0.08 and 3.74 ± 0.12 vs. 2.79 ± 0.02), along with Pb concentrations (10.6 ppb and 15.24 ppb) above the WHO-permitted level of 10 ppb in tap water, while the remaining four unknowns showed no detectable Pb upon ICP-MS. These results demonstrate that pMet-lead provides a rapid, sensitive means for on-site Pb detection in water from the environment and in living/drinking supply systems to prevent potential Pb poisoning.

Evaluation of the diagnostic accuracy of COVID-19 antigen tests: A systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect countries worldwide. To inhibit the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), testing of patients, contact tracing, and quarantine of their close contacts have been used as major nonpharmaceutical interventions. The advantages of antigen tests, such as low cost and rapid turnaround, may allow for the rapid identification of larger numbers of infectious persons. This meta-analysis aimed to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. METHODS: We searched PubMed, Embase, Cochrane Library, and Biomed Central databases from inception to January 2, 2021. Studies evaluating the diagnostic accuracy of antigen testing for SARS-CoV-2 with reference standards were included. We included studies that provided sufficient data to construct a 2 × 2 table on a per-patient basis. Only articles in English were reviewed. Summary sensitivity and specificity for antigen tests were generated using a random-effects model. RESULTS: Fourteen studies with 8624 participants were included. The meta-analysis for antigen testing generated a pooled sensitivity of 79% (95% CI, 66%-88%; 14 studies, 8624 patients) and a pooled specificity of 100% (95% CI, 99%-100%; 14 studies, 8624 patients). The subgroup analysis of studies that reported specimen collection within 7 days after symptom onset showed a pooled sensitivity of 95% (95% CI, 78%-99%; four studies, 1342 patients) and pooled specificity of 100% (95% CI, 97%-100%; four studies, 1342 patients). Regarding the applicability, the patient selection, index tests, and reference standards of studies in our meta-analysis matched the review title. CONCLUSION: Antigen tests have moderate sensitivity and high specificity for the detection of SARS-CoV-2. Antigen tests might have a higher sensitivity in detecting SARS-CoV-2 within 7 days after symptom onset. Based on our findings, antigen testing might be an effective method for identifying contagious individuals to block SARS-CoV-2 transmission.

Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Development and optimization of heavy metal lead biosensors in biomedical and environmental applications.

The detrimental impact of the heavy metal lead (Pb) on human health has been studied for years. The fact that Pb impairs human body has been established from countless painful and sad historical events. Nowadays, World Health Organization and many developmental countries have established regulations concerning the use of Pb. Measuring the blood lead level (BLL) is so far the only way to officially evaluate the degree of Pb exposure, but the so-called safety value (10 µg/dL in adults and 5 µg/dL in children) seems unreliable to represent the security checkpoint for children through daily intake of drinking water or physical contact with a lower contaminated level of Pb contents. In general, unsolved mysteries about the Pb toxicological mechanisms still remain. In this review article, we report on the methods to prevent Pb poison for further Pb toxicological research. We establish high-sensitivity Pb monitoring, and also report on the use of fluorescent biosensors such as genetically-encoded fluorescence resonance energy transfer-based biosensors built for various large demands such as the detection of severe acute respiratory syndrome coronavirus 2. We also contribute to the development and optimization of the FRET-based Pb biosensors. Our well-performed version of Met-lead 1.44 M1 has achieved a limit of detection of 10 nM (2 ppb; 0.2 µg/dL) and almost 5-fold in dynamic range (DR) supported for the real practical applications-that is, the in-cell Pb sensing device for blood and blood-related samples, and the Pb environmental detections in vitro. The perspective of our powerful Pb biosensor incorporated with a highly sensitive bio-chip of the portable device for quick Pb measurements will be addressed for further manipulation.

Extracorporeal membrane oxygenation (ECMO) for critically ill patients with coronavirus disease 2019 (COVID-19): A retrospective cohort study.

PURPOSE: The role of extracorporeal membrane oxygenatio (ECMO) for rescue therapy of respiratory failure in critically ill coronavirus disease 2019 (COVID-19) patients remains controversial. We aimed to evaluate the clinical outcomes of ECMO in the treatment of COVID-19 compared with conventional ventilation support. METHODS: In this retrospective cohort study, data were collected on extremely critical patients with COVID-19 from January 2020 to March 2020 in intensive care unit of a hospital in charge by national rescue team in Wuhan, China, the epicenter of pandemic. Patients were classified into the ECMO group and the conventional ventilation non-ECMO group. Clinical characteristics, technical characteristics, laboratory results, mortality, and complications of the two groups were analyzed. RESULTS: 88 patients with extremely critical COVID-19 were screened; 34 received ECMO support and 31 received conventional ventilation support. Both groups had comparable characteristics at baseline in terms of age, gender, and comorbidities. Before ECMO or conventional therapy, patients in the two groups had sever acute respiratory distress syndrome with a mean partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2 /FiO2 ) ratio of 69.6 and 75.4, respectively. At the time of reporting, patients in the ECMO had significantly lower in-hospital mortality compared with the control group (58.8 vs. 93.5%, p = .001). CONCLUSION: ECMO is shown to decrease the mortality of extremely critical ill COVID-19 patients compared with the conventional treatment. Although complications occurred frequently, ECMO could still be a rescue therapy for the treatment of COVID-19 during the pandemic.

Modifications of intravitreal injections in response to the COVID-19 pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruption to the normal operation of the healthcare system. On a worldwide scale, hospitals suspended nonurgent surgeries and outpatient visits to downsize clinical loadings to redistribute manpower to counteract the pandemic's impact. So far, there is no evidence-based guideline defining a clear line between urgent and nonurgent indications of intravitreal injections (IVI). Herein, we aimed to summarize IVI algorithm modifications and discuss the patient prioritization according to medical needs in the hostile environment in the COVID crisis. Assessing current literature, we found that neovascular age-related macular degeneration is considered the utmost priority among conditions that require IVI. Other conditions assigned with a high priority include monocular or quasi-monocular patients (only one eye > 20/40), neovascular glaucoma, and new patients with significant vision loss. Although patients with central retinal vein occlusion and proliferative diabetic retinopathy are not advised to delay treatments, we found no consistent evidence that correlated with a worse outcome. Diabetic macular edema and branch retinal vein occlusion patients undertaking treatment delay should be regularly followed up every 2 to 3 months. Serving as the principle of management behind the algorithm modifications, the reduction of both patient visit and IVI therapy counts should be reckoned together with the risk of permanent visual loss and COVID infection.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Consensus on Pre-examination and Triage in Clinic of Dermatology During Outbreak of COVID-19 From Chinese Experts.

The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.

Clinical manifestation and disease progression in COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.

Highlight of severe acute respiratory syndrome coronavirus-2 vaccine development against COVID-19 pandemic.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.

Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties (preprint)

The recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients (preprint)

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.