SARS-CoV-2 pandemics: An update of CRISPR in diagnosis and host–virus interaction studies

Since December 2019, the Coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread rapidly around the world, overburdening healthcare systems and creating significant global health concerns. Rapid detection of infected individuals via early diagnostic tests and administration of effective therapy remains vital in pandemic control, and recent advances in the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated proteins) system may support the development of novel diagnostic and therapeutic approaches. Cas-based SARS-CoV-2 detection methods (FELUDA, DETECTR, and SHERLOCK) have been developed for easier handling compared to quantitative polymerase chain reaction (qPCR) assays, with good rapidity, high specificity, and reduced need for complex instrumentation. Cas-CRISPR-derived RNA (Cas-crRNA) complexes have been shown to reduce viral loads in the lungs of infected hamsters, by degrading virus genomes and limiting viral replication in host cells. Viral-host interaction screening platforms have been developed using the CRISPR-based system to identify essential cellular factors involved in pathogenesis, and CRISPR knockout and activation screening results have revealed vital pathways in the life cycle of coronaviruses, including host cell entry receptors (ACE2, DPP4, and ANPEP), proteases involved in spike activation and membrane fusion (CTSL and TMPRSS2), intracellular traffic control routes for virus uncoating and budding, and membrane recruitment for viral replication. Several novel genes (SMARCA4, ARIDIA, and KDM6A) have also been identified via systematic data mining analysis as pathogenic factors for severe CoV infection. This review highlights how CRISPR-based systems can be applied to investigate the viral life cycle, detect viral genomes, and develop therapies against SARS-CoV-2 infection.

SARS-CoV-2 pandemics: An update of CRISPR in diagnosis and host-virus interaction studies.

Since December 2019, the Coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread rapidly around the world, overburdening healthcare systems and creating significant global health concerns. Rapid detection of infected individuals via early diagnostic tests and administration of effective therapy remains vital in pandemic control, and recent advances in the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins (Cas) system may support the development of novel diagnostic and therapeutic approaches. Cas-based SARS-CoV-2 detection methods (FnCAS9 Editor Linked Uniform Detection Assay (FELUDA), DNA endonuclease-targeted CRISPR trans reporter (DETECTR), and Specific High-sensitivity Enzymatic Reporter Unlocking (SHERLOCK)) have been developed for easier handling compared to quantitative polymerase chain reaction (qPCR) assays, with good rapidity, high specificity, and reduced need for complex instrumentation. Cas-CRISPR-derived RNA (Cas-crRNA) complexes have been shown to reduce viral loads in the lungs of infected hamsters, by degrading virus genomes and limiting viral replication in host cells. Viral-host interaction screening platforms have been developed using the CRISPR-based system to identify essential cellular factors involved in pathogenesis, and CRISPR knockout (CRISPRKO) and activation screening results have revealed vital pathways in the life cycle of coronaviruses, including host cell entry receptors (ACE2, DPP4, and ANPEP), proteases involved in spike activation and membrane fusion (cathepsin L (CTSL) and transmembrane protease serine 2 (TMPRSS2)), intracellular traffic control routes for virus uncoating and budding, and membrane recruitment for viral replication. Several novel genes (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, subfamily A, member 4 (SMARCA4), ARIDIA, and KDM6A) have also been identified via systematic data mining analysis as pathogenic factors for severe CoV infection. This review highlights how CRISPR-based systems can be applied to investigate the viral life cycle, detect viral genomes, and develop therapies against SARS-CoV-2 infection.

Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.

Maternal-Neonatal Outcomes of Obstetric Deliveries Performed in Negative Pressure Isolation Rooms during the COVID-19 Omicron Variant Pandemic in Taiwan: A Retrospective Cohort Study of a Single Institution.

Objective: To investigate the maternal-neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal-neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.

Lymphocyte count is a universal predictor of health outcomes in COVID-19 patients before mass vaccination: A meta-analytical study.

Background: Several laboratory data have been identified as predictors of disease severity or mortality in COVID-19 patients. However, the relative strength of laboratory data for the prediction of health outcomes in COVID-19 patients has not been fully explored. This meta-analytical study aimed to evaluate the prediction capabilities of laboratory data on the prognosis of COVID-19 patients during 2020 while mass vaccination has not started yet. Methods: Two electronic databases, MEDLINE and EMBASE, from inception to October 10, 2020 were searched. Observational studies of laboratory-confirmed COVID-19 patients with well-defined severity or survival status, and with the desired laboratory data at initial hospital administrations, were selected. Meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. Primary outcome measures were to compare the level of laboratory data and their impact on different health outcomes (severe vs non-severe, critically severe vs non-critically severe, and dead vs alive). Results: Meta-data of 13 clinical laboratory items at initial hospital presentations were extracted from 76 selected studies with a total of 26 627 COVID-19 patients in 16 countries. After adjusting for the effect of age, 1.03 0.87 (OR = 0.0576; 95% CI = 0.0043-0.4726; P = 0.0079) had a much lower risk of severity, critical severity, and mortality from COVID-19, respectively. Conclusions: Lymphocyte count was the most powerful predictor among the 13 common laboratory variables explored from COVID-19 patients to differentiate disease severity and to predict mortality. Lymphocyte count should be monitored for the prognoses of COVID-19 patients in clinical settings in particular for patients not fully vaccinated.

Performance evaluation of antigen detection rapid diagnostic test (Ag-RDT) for COVID-19 diagnosis in a primary healthcare center during the Shanghai COVID-19 quarantine period.

BACKGROUND: Rapid and accurate detection of SARS-CoV-2 infection is the cornerstone of prompt patient care. However, the reliability of the antigen rapid diagnostic test (Ag-RDT) in the diagnosis of SARS-CoV-2 infection remains inconclusive. METHODS: We conducted a field evaluation of Ag-RDT performance during the Shanghai Coronavirus disease 2019 (COVID-19) quarantine and screened 7225 individuals visiting our Emergency Department. 83 asymptomatic SARS-CoV-2 (+) individuals were enrolled in the current study. Simultaneously, Ag-RDT was performed to evaluate its testing performance. RESULTS: For the Ag-RDT(-) cases, the average cycle threshold (Ct) values of the N gene were 27.26 ± 4.59, which were significantly higher than the Ct value (21.9 ± 4.73) of the Ag-RDT(+) individuals (p < 0.0001). The overall sensitivity of Ag-RDT versus that of RT-PCR was 43.37%. The Ag-RDT(+) individuals regarding the N gene's Ct value were 16 cases in the < 20 range, 12 in 20-25, 5 in 25-30, and 3 in 30-35. The corresponding sensitivity was 84.21%, 52.17%, 21.74% and 16.67%, respectively. Meanwhile, sampling had a straight specificity of 100% regardless of the Ct value. CONCLUSIONS: The Ag-RDT were extremely sensitive in asymptomatic COVID-19 individuals with a Ct value < 20.

Delayed Skin Reactions to COVID-19 mRNA-1273 Vaccine: Case Report and Literature Review.

BACKGROUND: The COVID-19 mRNA vaccine was granted emergency use authorization (EUA) on December 18, 2020. Some patients experienced a transient, pruritic rash at the injection site, which was referred to as "COVID arm". It is considered a delayed-type hypersensitivity reaction and occurs mostly in individuals after vaccination with the Moderna vaccine but rarely with other mRNA vaccines. CASE SUMMARY: A healthy 33-year-old woman with no history of disease or long-term medication presented with fever and rash on the left upper arm three days after her first vaccination with the mRNA-1273 vaccine (Moderna). RESULTS: After treatment with antihistamines, all lesions gradually resolved over the following 4 to 5 days. CONCLUSION: We report a case of "COVID arm": a localized erythematous rash surrounding the injection site that arose three days after the first dose of the Moderna COVID-19 vaccine. Delayed injection site reactions occurred in approximately 0.8% of vaccinated people after the first dose and in approximately 0.2% after the second dose. The lesions persisted for several days and then resolved without treatment. Health care providers were not prepared to address these delayed local reactions to the mRNA-1273 vaccine. Given the scale-up of mass vaccination campaigns worldwide, these skin reactions may likely generate concerns among patients and requests for evaluation. Although these skin reactions have not been consistently recognized, guidance regarding the second dose of the vaccine has varied, and many patients have unnecessarily received antibiotic agents.

Clinical Manifestation, Management, and Outcomes in Patients with COVID-19 Vaccine-Induced Acute Encephalitis: Two Case Reports and a Literature Review.

INTRODUCTION: Vaccination is one of the best strategies to control coronavirus disease 2019 (COVID-19), and multiple vaccines have been introduced. A variety of neurological adverse effects have been noted after the implementation of large-scale vaccination programs. METHODS: We reported two rare cases of possible mRNA-1273 vaccine-induced acute encephalitis, including clinical manifestations, laboratory characteristics, and management. RESULTS: The clinical manifestations might be related to hyperproduction of systemic and cerebrospinal fluid (CSF) cytokines. mRNA vaccines are comprised of nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA, which is translated into SARS-CoV-2 spike protein by the host's ribosomes, activating the adaptive immune response. Exposed mRNA or vaccine components may also be detected as antigens, further resulting in aberrant proinflammatory cytokine cascades and activation of immune signaling pathways. Both patients exhibited significant clinical improvement after a course of steroid therapy. CONCLUSIONS: The use of COVID-19 vaccines to prevent and control SARS-CoV-2 infections and complications is the most practicable policy worldwide. However, inaccurate diagnosis or other diagnostic delays in cases of vaccine-induced acute encephalitis may have devastating and potentially life-threatening consequences for patients. Early diagnosis and timely treatment can result in a favorable prognosis.

Suicidality in clinically stable bipolar disorder and schizophrenia patients during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has a disproportionate impact on vulnerable subpopulations, including those with severe mental illness (SMI). This study examined the one-year prevalence of suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) in bipolar disorder (BD) and schizophrenia (SCZ) patients during the pandemic. Prevalence rates were compared between the two disorders and associated factors were examined. A survey was conducted in six tertiary psychiatric hospitals and psychiatric units. People with a diagnosis of BD or SCZ were invited to participate. SI, SP, and SA (suicidality for short) were assessed and associated factors were examined using binary logistical regression. The 1-year prevalence of SI, SP and SA in BD patients were 58.3%, (95% CI: 54.1-62.6%), 38.4% (95% CI: 34.3-42.6%) and 38.6% (95% CI: 34.5-42.8%), respectively, which were higher than the corresponding figures in SCZ patients (SI: 33.2%, 95% CI: 28.6-37.8%; SP: 16.8%, 95% CI: 13.2-20.5%; SA: 19.4%, 95% CI: 15.5-23.3%). Patients with younger age, experience of cyberbullying, a history of SA among family or friends, a higher fatigue and physical pain score, inpatient status, and severe depressive symptoms were more likely to have suicidality. The COVID-19 pandemic was associated with increased risk of suicidality, particularly in BD patients. It is of importance to regularly screen suicidality in BD and SCZ patients during the pandemic even if they are clinically stable.

The Impact of Consumers' Loneliness and Boredom on Purchase Intention in Live Commerce During COVID-19: Telepresence as a Mediator.

This paper examines the relationship between consumer loneliness, boredom, telepresence, influencer-brand image congruence and purchase intention by investigating consumers of live commerce during the COVID-19 period. With the help of an online survey website, survey data was gathered on 550 Chinese customers who experienced live commerce shopping in China. Although previous studies have shown that consumer boredom and loneliness have an impact on purchase intention, the mechanism of influence remains unclear. As a result, additional research is needed to study the link between boredom and loneliness and customer purchase intention. Consumers' purchase intention was influenced by their feelings of loneliness and boredom. Telepresence played a mediating role in the impact of loneliness and boredom on purchase intention. Influencer-brand image congruence played a moderating role in the impact of consumers' boredom on purchase intention. The study results contribute to the research of factors impacting consumers' purchase intention. In addition, this study can help live commerce merchants better understand the impact factors of consumers' purchase intention and contribute to the development of live commerce.

Vitamin D for Recovery of COVID-19 in Patients With Chronic Kidney Disease

The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.

The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

Prevalence of suicidality in clinically stable patients with major depressive disorder during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is associated with an increased risk of mental health problems including suicide in many subpopulations, but its influence on stable patients with major depressive disorder (MDD) has been studied fleetingly. This study examined the one-year prevalence of suicidality including suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) as well as their correlates in clinically stable MDD patients during the COVID-19 pandemic. METHODS: A cross-sectional, observational study was conducted between October 1, 2020, and October 15, 2021, in six tertiary psychiatric hospitals. Socio-demographic information, clinical data and one-year prevalence of suicidality were recorded. RESULTS: Altogether, 1718 participants who met the eligibility criteria were included. The overall one-year prevalence of suicidality during the COVID-19 pandemic was 68.04% (95% confidence intervals (CI) =65.84-70.25%), with one-year SI prevalence of 66.4% (95%CI = 64.18-68.65%), SP prevalence of 36.26% (95%CI = 33.99-38.54%), and SA prevalence of 39.35% (95%CI = 37.04-41.66%). Binary logistic regression analyses revealed male gender, married marital status, college education level and above and age were negatively associated with risk of suicidality. Urban residence, unemployed work status, experiences of cyberbullying, a history of suicide among family members or friends, and more severe fatigue, physical pain, and residual depressive symptoms were positively associated with risk of suicidality. CONCLUSIONS: Suicidality is common among clinically stable MDD patients during the COVID-19 pandemic. Regular suicide screening and preventive measures should be provided to clinically stable MDD patients during the pandemic.

Exploring New Characteristics: Using Deep Learning and 3D Reconstruction to Compare the Original COVID-19 and Its Delta Variant Based on Chest CT.

Purpose: Computer-aided diagnostic methods were used to compare the characteristics of the Original COVID-19 and its Delta Variant. Methods: This was a retrospective study. A deep learning segmentation model was applied to segment lungs and infections in CT. Three-dimensional (3D) reconstruction was used to create 3D models of the patient's lungs and infections. A stereoscopic segmentation method was proposed, which can subdivide the 3D lung into five lobes and 18 segments. An expert-based CT scoring system was improved and artificial intelligence was used to automatically score instead of visual score. Non-linear regression and quantitative analysis were used to analyze the dynamic changes in the percentages of infection (POI). Results: The POI in the five lung lobes of all patients were calculated and converted into CT scores. The CT scores of Original COVID-19 patients and Delta Variant patients since the onset of initial symptoms were fitted over time, respectively. The peak was found to occur on day 11 in Original COVID-19 patients and on day 15 in Delta Variant patients. The time course of lung changes in CT of Delta Variant patients was redetermined as early stage (0-3 days), progressive and peak stage (4-16 days), and absorption stage (17-42 days). The first RT-PCR negative time in Original COVID-19 patients appeared earlier than in Delta Variant patients (22 [17-30] vs. 39 [31-44], p < 0.001). Delta Variant patients had more re-detectable positive RT-PCR test results than Original COVID-19 patients after the first negative RT-PCR time (30.5% vs. 17.1%). In the early stage, CT scores in the right lower lobe were significantly different (Delta Variant vs. Original COVID-19, 0.8 ± 0.6 vs. 1.3 ± 0.6, p = 0.039). In the absorption stage, CT scores of the right middle lobes were significantly different (Delta Variant vs. Original COVID-19, 0.6 ± 0.7 vs. 0.3 ± 0.4, p = 0.012). The left and the right lower lobes contributed most to lung involvement at any given time. Conclusion: Compared with the Original COVID-19, the Delta Variant has a longer lung change duration, more re-detectable positive RT-PCR test results, different locations of pneumonia, and more lesions in the early stage, and the peak of infection occurred later.

Non-Pharmaceutical Interventions Implemented to Control the COVID-19 Were Associated With Reduction of Influenza Incidence.

BACKGROUND: Non-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019-2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza. METHODS: We used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore. RESULTS: We found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019-2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50-99.48% during the period of compulsory interventions in the 2019-2020 season compared to the same period in preceding years in the four countries. CONCLUSION: These findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

Comparison of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis: Report of the clinical scenario and literature review.

BACKGROUND: Pulmonary cryptococcosis is an opportunistic aggressive mycosis in immunocompromised patients, but it can be increasingly seen in immunocompetent patients. It is still challenging to make a rapid and accurate diagnosis due to the various clinical manifestations and limitations in the diagnostic tools. METHOD: A 54-year-old man presented with intermittent productive cough and fever for 1 week. A chest X-ray demonstrated multiple consolidations in both lungs. Blood biochemistry indicated elevated immunoglobulin G levels. Including sputum cultures, polymerase chain reaction (PCR) tests for severe acute respiratory syndrome coronavirus 2, influenza A and B virus were all negative. Computed tomography of the chest showed ground-glass opacities with a nodular pattern. The serum cryptococcal antigen test was positive; however, the cerebral spinal fluid was negative. The diagnosis of pulmonary cryptococcal infection was made. An initial bronchoscopy was performed unsuccessfully and the patient received intravenous fluconazole therapy for 2 weeks. Due to poor improvement of clinical condition, he then underwent a surgical lung biopsy. The pathology revealed several encapsulated yeast cells, diffuse pulmonary interstitial fibrosis, noncaseating granulomas surrounded by T lymphocytes and multinucleated giant cells with intracellular inclusions, confirming pulmonary yeast infection associated with hypersensitivity pneumonitis. Ultimately, fungal cultures of the pathology samples revealed Cryptococcus neoformans. Subsequently antifungal therapy combined with oral steroid treatment, his general condition improved. After a total of 6 months of antifungal therapy, the patient recovered completely. CONCLUSIONS: Applicable laboratory diagnosis can help facilitate the accurate and rapid diagnosis of pulmonary cryptococcosis. This report elected to provide an update on the topic of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis.

A Cloud-Edge-Terminal Collaborative System for Temperature Measurement in COVID-19 Prevention (preprint)

To prevent the spread of coronavirus disease 2019 (COVID-19), preliminary temperature measurement and mask detection in public areas are conducted. However, the existing temperature measurement methods face the problems of safety and deployment. In this paper, to realize safe and accurate temperature measurement even when a person's face is partially obscured, we propose a cloud-edge-terminal collaborative system with a lightweight infrared temperature measurement model. A binocular camera with an RGB lens and a thermal lens is utilized to simultaneously capture image pairs. Then, a mobile detection model based on a multi-task cascaded convolutional network (MTCNN) is proposed to realize face alignment and mask detection on the RGB images. For accurate temperature measurement, we transform the facial landmarks on the RGB images to the thermal images by an affine transformation and select a more accurate temperature measurement area on the forehead. The collected information is uploaded to the cloud in real time for COVID-19 prevention. Experiments show that the detection model is only 6.1M and the average detection speed is 257ms. At a distance of 1m, the error of indoor temperature measurement is about 3%. That is, the proposed system can realize real-time temperature measurement in public areas.

Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation.

BACKGROUND: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM. METHODS: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay. RESULTS: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir. CONCLUSION: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.