Olfactory and gustatory dysfunctions of COVID-19 patients in China: A multicenter study.

Introduction: With the spread of the epidemic worldwide, an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019 (COVID-19): olfactory or taste disorders. Therefore, clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID-19 patients is of great significance and urgency. Materials and Methods: A retrospective study was conducted, which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients, through face-to-face interviews and telephone follow-up. Following the completion of questionnaires, the patients participating in the study, were categorized according to the degree of olfactory and taste disorders experienced, and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded. Results: Among the 229 patients, 31 (13.54%) had olfactory dysfunction, and 44 (19.21%) had gustatory dysfunction. For the patients with olfactory dysfunction, 6 (19.35%) developed severe disease and became critically ill. Olfactory dysfunction appeared before the other symptoms in 21.43% of cases. The proportion of females with olfactory and gustatory dysfunction was higher than that of males (P < 0.001). Conclusions: The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad; the prognosis of patients with olfactory dysfunction is relatively favorable; olfactory and gustatory dysfunction can be used as a sign for early screening; females are more prone to olfactory and gustatory dysfunction.

Thought and prospect of safety clinical transfusion under major public health emergency

As of the end of January 2020, 31 provinces, municipalities and autonomous regions across the country had activated their Level 1 responses to major public health emergencies due to the outbreak of the novel coronavirus. Under the state of emergency prevention and control, work and production were suspended, cities and roads were closed, people were isolated at home, blood donations were cancelled, and blood stock management was severely tested. If the epidemic continues to develop or an unknown public health event occurs, it is imperative that blood collection agencies and hospital transfusion departments at all levels respond in a safe and effective manner to safeguard the clinical blood supply. This article summarises the measures that can be taken to ensure adequate blood stocks and the safety of blood collection and supply in the event of a major public health emergency, with a view to providing new ideas for clinical blood collection and supply and safe clinical blood use.

NLRP3 Inflammasome: Mechanism of Action, Role, and Therapeutics in Liver Diseases (preprint)

Liver inflammation is a universal characteristic of chronic liver diseases. NLRP3 is an intracellular sensor that recognizes various endogenous danger signals and environmental irritants, contributing to the formation and activation of the NLRP3 inflammasome. NLRP3 inflammasome is closely related to the progression of various liver diseases and is strongly associated with replicating COVID-19, which is still spreading globally. The assembly and activation of NLRP3 inflammasome in the liver diseases aggravate inflammation and subsequent fibrosis, and this effect is abolished by genetic or pharmacologic deletion of NLRP3 inflammasome. Here, we summarized the latest advances in the critical regulatory role of NLRP3 inflammasome in a variety of liver diseases, including COVID-19 induced liver diseases, NAFLD, ALD, and ischemia-reperfusion (I/R) injury. Additionally, we also discuss small-molecule inhibitors identifying the NLRP3 inflammasome signaling are novel therapeutic targets in treating liver diseases. Our review provides novel insights into the underlying mechanisms of NLRP3 inflammasome in liver diseases and may offer a potential therapeutic strategy for treating liver diseases by targeting NLRP3 inflammasome.

A cross-sectional study of olfactory and taste disorders among COVID-19 patients in China.

To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.

An Empirical Evaluation of Bluetooth-based Decentralized Contact Tracing in Crowds (preprint)

Digital contact tracing is being used by many countries to help contain COVID-19's spread in a post-lockdown world. Among the various available techniques, decentralized contact tracing that uses Bluetooth received signal strength indication (RSSI) to detect proximity is considered less of a privacy risk than approaches that rely on collecting absolute locations via GPS, cellular-tower history, or QR-code scanning. As of October 2020, there have been millions of downloads of such Bluetooth-based contract-tracing apps, as more and more countries officially adopt them. However, the effectiveness of these apps in the real world remains unclear due to a lack of empirical research that includes realistic crowd sizes and densities. This study aims to fill that gap, by empirically investigating the effectiveness of Bluetooth-based contact tracing in crowd environments with a total of 80 participants, emulating classrooms, moving lines, and other types of real-world gatherings. The results confirm that Bluetooth RSSI is unreliable for detecting proximity, and that this inaccuracy worsens in environments that are especially crowded. In other words, this technique may be least useful when it is most in need, and that it is fragile when confronted by low-cost jamming. Moreover, technical problems such as high energy consumption and phone overheating caused by the contact-tracing app were found to negatively influence users' willingness to adopt it. On the bright side, however, Bluetooth RSSI may still be useful for detecting coarse-grained contact events, for example, proximity of up to 20m lasting for an hour. Based on our findings, we recommend that existing contact-tracing apps can be re-purposed to focus on coarse-grained proximity detection, and that future ones calibrate distance estimates and adjust broadcast frequencies based on auxiliary information.

Clinical characteristics of neonates with coronavirus disease 2019 (COVID-19): a systematic review (preprint)

This study aimed to summarize the existing literature on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in newborns to clarify the clinical features and outcomes of neonates with COVID-19. A systematic search was performed in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP databases from January 1, 2019 to April 30, 2020. The references of relevant studies were also searched. A descriptive summary was organized by aspects of clinical presentations (symptoms, laboratory examinations, and imaging) and outcomes. We identified 14 studies reporting 18 newborns with COVID-19. The most common clinical manifestations were fever (62.5%), shortness of breath (50.0%), diarrhea/vomiting/feeding intolerance(43.8%), cough (37.5%), dyspnea (25.0%), and nasal congestion/runny nose/sneeze(25.0%). Atypical symptoms included jaundice and convulsion. Lymphocyte numbers decreased in 5 cases, and radiographic findings were likely to show pneumonia. All newborns recovered and discharged from the hospital, and there was no death.Conclusion: Clinical symptoms of neonatal SARS-CoV-2 infection are atypical, most of them are mild. Up to now, the prognosis of newborns is good, and there is no death. Intrauterine vertical transmission is possible, but confirmed evidence is still lacking. The Long-term follow-up of potential influences of SARS-CoV-2 infection on neonates need further exploration.

Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission associated with increased mortality in Western Europe and the United States (preprint)

Mechanisms underlying the acute respiratory distress syndrome (ARDS)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.

Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice (preprint)

Background We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of serocon-version for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of IgG seroconversion and [≥] 4-fold increase in the IgG titers in sequential samples together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or [≥] 4-fold increase in the IgG titer is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.

A Peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Corona Virus Disease 2019 (COVID-19) (preprint)

A respiratory illness has been spreading rapidly in China, since its outbreak in Wuhan city, Hubei province in December 2019. The illness was caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations related to SARS-CoV-2 infection ranged from no symptom to fatal pneumonia. World Health Organization (WHO) named the diseases associated with SARS-CoV-2 infection as COVID-19. Real time RT-PCR is the only laboratory test available till now to confirm the infection. However, the accuracy of real time RT-PCR depends on many factors, including sampling location and of methods, quality of RNA extraction and training of operators etc. Variations in these factors might significantly lower the sensitivity of the detection. We developed a peptide-based luminescent immunoassay to detect IgG and IgM. Cut-off value of this assay was determined by the detection of 200 healthy sera and 167 sera from patients infected with other pathogens than SARS-CoV-2. To evaluate the performance of this assay, we detected IgG and IgM in the 276 sera from confirmed patients. The positive rate of IgG and IgM were 71.4% (197/276) and 57.2% (158/276) respectively. By combining with real time RT-PCR detection, this assay might help to enhance the accuracy of diagnosis of SARS-CoV-2 infection.