Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Biological Actions, Implications, and Cautions of Statins Therapy in COVID-19.

The Coronavirus Disease 2019 (COVID-19) showed worse prognosis and higher mortality in individuals with obesity. Dyslipidemia is a major link between obesity and COVID-19 severity. Statins as the most common lipid regulating drugs have shown favorable effects in various pathophysiological states. Importantly, accumulating observational studies have suggested that statin use is associated with reduced risk of progressing to severe illness and in-hospital death in COVID-19 patients. Possible explanations underlie these protective impacts include their abilities of reducing cholesterol, suppressing viral entry and replication, anti-inflammation and immunomodulatory effects, as well as anti-thrombosis and anti-oxidative properties. Despite these benefits, statin therapies have side effects that should be considered, such as elevated creatinine kinase, liver enzyme and serum glucose levels, which are already elevated in severe COVID-19. Concerns are also raised whether statins interfere with the efficacy of COVID-19 vaccines. Randomized controlled trials are being conducted worldwide to confirm the values of statin use for COVID-19 treatment. Generally, the results suggest no necessity to discontinue statin use, and no evidence suggesting interference between statins and COVID-19 vaccines. However, concomitant administration of statins and COVID-19 antiviral drug Paxlovid may increase statin exposure and the risk of adverse effects, because most statins are metabolized mainly through CYP3A4 which is potently inhibited by ritonavir, a major component of Paxlovid. Therefore, more clinical/preclinical studies are still warranted to understand the benefits, harms and mechanisms of statin use in the context of COVID-19.

Well-being analysis favours a virus-elimination strategy for COVID-19

A well-being approach requires looking beyond COVID-19 deaths to compare the performance of elimination versus mitigation strategies as measured by other important supports for well-being. What do the data show? Our comparison based on 2020 data shows a virus elimination strategy to be more successful than other options, whether measured in terms of COVID-19 deaths, overall excess deaths, income, unemployment, trust, or mental and physical health. Countries that chose and followed a strategy of reducing community transmission to zero and keeping it there saved lives and better protected income and employment, all without obvious costs to either the social fabric or the mental health of their populations.

Poly-l-Lysine-Modified Graphene Field-Effect Transistor Biosensors for Ultrasensitive Breast Cancer miRNAs and SARS-CoV-2 RNA Detection.

(Mi)RNAs are important biomarkers for cancers diagnosis and pandemic diseases, which require fast, ultrasensitive, and economical detection strategies to quantitatively detect exact (mi)RNAs expression levels. The novel coronavirus disease (SARS-CoV-2) has been breaking out globally, and RNA detection is the most effective way to identify the SARS-CoV-2 virus. Here, we developed an ultrasensitive poly-l-lysine (PLL)-functionalized graphene field-effect transistor (PGFET) biosensor for breast cancer miRNAs and viral RNA detection. PLL is functionalized on the channel surface of GFET to immobilize DNA probes by the electrostatic force. The results show that PGFET biosensors can achieve a (mi)RNA detection range of five orders with a detection limit of 1 fM and an entire detection time within 20 min using 2 µL of human serum and throat swab samples, which exhibits more than 113% enhancement in terms of sensitivity compared to that of GFET biosensors. The performance enhancement mechanisms of PGFET biosensors were comprehensively studied based on an electrical biosensor theoretical model and experimental results. In addition, the PGFET biosensor was applied for the breast cancer miRNA detection in actual serum samples and SARS-CoV-2 RNA detection in throat swab samples, providing a promising approach for rapid cancer diagnosis and virus screening.

Data-driven multi-scale mathematical modeling of SARS-CoV-2 infection reveals heterogeneity among COVID-19 patients.

Patients with coronavirus disease 2019 (COVID-19) often exhibit diverse disease progressions associated with various infectious ability, symptoms, and clinical treatments. To systematically and thoroughly understand the heterogeneous progression of COVID-19, we developed a multi-scale computational model to quantitatively understand the heterogeneous progression of COVID-19 patients infected with severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). The model consists of intracellular viral dynamics, multicellular infection process, and immune responses, and was formulated using a combination of differential equations and stochastic modeling. By integrating multi-source clinical data with model analysis, we quantified individual heterogeneity using two indexes, i.e., the ratio of infected cells and incubation period. Specifically, our simulations revealed that increasing the host antiviral state or virus induced type I interferon (IFN) production rate can prolong the incubation period and postpone the transition from asymptomatic to symptomatic outcomes. We further identified the threshold dynamics of T cell exhaustion in the transition between mild-moderate and severe symptoms, and that patients with severe symptoms exhibited a lack of naïve T cells at a late stage. In addition, we quantified the efficacy of treating COVID-19 patients and investigated the effects of various therapeutic strategies. Simulations results suggested that single antiviral therapy is sufficient for moderate patients, while combination therapies and prevention of T cell exhaustion are needed for severe patients. These results highlight the critical roles of IFN and T cell responses in regulating the stage transition during COVID-19 progression. Our study reveals a quantitative relationship underpinning the heterogeneity of transition stage during COVID-19 progression and can provide a potential guidance for personalized therapy in COVID-19 patients.

Well-being Analysis Favours a Virus-Elimination Strategy for COVID-19

A well-being approach requires looking beyond COVID-19 deaths to compare the performance of elimination versus mitigation strategies as measured by other important supports for well-being. What do the data show? Our comparison based on 2020 data shows a virus elimination strategy to be more successful than other options, whether measured in terms of COVID-19 deaths, overall excess deaths, income, unemployment, trust, or mental and physical health. Countries that chose and followed a strategy of reducing community transmission to zero and keeping it there saved lives and better protected income and employment, all without obvious costs to either the social fabric or the mental health of their populations.

Manifestations of blood coagulation and its relation to clinical outcomes in severe COVID-19 patients: Retrospective analysis.

INTRODUCTION: Characteristics of blood coagulation and its relation to clinical outcomes in COVID-19 patients are still rarely reported. We aimed to investigate the blood coagulation function and its influences on clinical outcomes of patients with syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 71 severe patients with confirmed SARS-CoV-2 infection who were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled. The blood coagulation data in these patients and in 61 healthy controls were collected. The patients with COVID-19 were divided into two groups: the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission. RESULTS: Compared with healthy controls, patients with COVID-19 had significant performances with coagulation dysfunction, including dramatically elevated values of FIB, PT, APTT, INR, FDP, and D-Dimers but markedly reduced AT value (P < .05). Importantly, more noteworthy coagulation disorders similar to the differences between patients and controls were found in the aggravated patients with conditions deterioration after admission than those in the nonaggravated patients without conditions deterioration (P < .05). Moreover, the aggravated patients possessed a longer hospital stay and a higher mortality compared with the nonaggravated patients (P < .001). The coagulation parameters of COVID-19 patients were widely and closely related to the indexes of liver function and inflammation (P < .05), indicating the coagulation dysfunction of these patients may be caused by liver injury and inflammatory storm. CONCLUSION: Severe patients with SARS-CoV-2 infection often possess coagulation dysfunction on admission. A certain correlation exists in coagulation disorder and adverse clinical outcome among severe COVID-19 patients.