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The current coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health emergency of international concern. There has been a surge in demand for COVID-19 diagnostic reagents, as timely detection of virus carriers is one of the most important components of disease prevention and control. Nucleic acid testing (NAT), with high sensitivity and specificity, is considered the "gold standard" for the diagnosis of COVID-19. Therefore, more than 700 research units and companies have been devoted to developing NAT reagents. To date, nearly 600 research units and companies have claimed to have completed the development of NAT reagents. The use of these products has a positive effect on disease prevention and control; however, exaggerated claims and inadequate understanding of the products have led to improper access to reagents and equipment in clinics. This has resulted in chaos in the clinical diagnosis of COVID-19. Herein, we have overviewed the COVID-19 NAT products, including their principles, corresponding advantages and disadvantages, relevant circumstances for application, and respective roles in epidemic containment. Our comments may provide some references for assay developers and aid clinical staff in choosing the appropriate class of test from the different tests available.

As one of the major approaches in combating the COVID-19 pandemics, the availability of specific and reliable assays for the SARS-CoV-2 viral genome and its proteins is essential to identify the infection in suspected populations, make diagnoses in symptomatic or asymptomatic individuals, and determine clearance of the virus after the infection. For these purposes, use of the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for detection of the viral nucleic acid remains the most valuable in terms of its specificity, fast turn-around, high-throughput capacity, and reliability. It is critical to update the sequences of primers and probes to ensure the detection of newly emerged variants. Various assays for increased levels of IgG or IgM antibodies are available for detecting ongoing or past infection, vaccination responses, and persistence and for identifying high titers of neutralizing antibodies in recovered individuals. Viral genome sequencing is increasingly used for tracing infectious sources, monitoring mutations, and subtype classification and is less valuable in diagnosis because of its capacity and high cost. Nanopore target sequencing with portable options is available for a quick process for sequencing data. Emerging CRISPR-Cas-based assays, such as SHERLOCK and AIOD-CRISPR, for viral genome detection may offer options for prompt and point-of-care detection. Moreover, aptamer-based probes may be multifaceted for developing portable and high-throughput assays with fluorescent or chemiluminescent probes for viral proteins. In conclusion, assays are available for viral genome and protein detection, and the selection of specific assays depends on the purposes of prevention, diagnosis and pandemic control, or monitoring of vaccination efficacy., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Background: As the COVID-19 pandemic continues, national-level surveillance platforms with real-time individual person-level data are required to monitor and predict the epidemiological and clinical profile of COVID-19 and inform public health policy. We aimed to create a national dataset of patient-level data in Scotland to identify temporal trends and COVID-19 risk factors, and to develop a novel statistical prediction model to forecast COVID-19-related deaths and hospitalisations during the second wave., Methods: We established a surveillance platform to monitor COVID-19 temporal trends using person-level primary care data (including age, sex, socioeconomic status, urban or rural residence, care home residence, and clinical risk factors) linked to data on SARS-CoV-2 RT-PCR tests, hospitalisations, and deaths for all individuals resident in Scotland who were registered with a general practice on Feb 23, 2020. A Cox proportional hazards model was used to estimate the association between clinical risk groups and time to hospitalisation and death. A survival prediction model derived from data from March 1 to June 23, 2020, was created to forecast hospital admissions and deaths from October to December, 2020. We fitted a generalised additive spline model to daily SARS-CoV-2 cases over the previous 10 weeks and used this to create a 28-day forecast of the number of daily cases. The age and risk group pattern of cases in the previous 3 weeks was then used to select a stratified sample of individuals from our cohort who had not previously tested positive, with future cases in each group sampled from a multinomial distribution. We then used their patient characteristics (including age, sex, comorbidities, and socioeconomic status) to predict their probability of hospitalisation or death., Findings: Our cohort included 5 384 819 people, representing 98·6% of the entire estimated population residing in Scotland during 2020. Hospitalisation and death among those testing positive for SARS-CoV-2 between March 1 and June 23, 2020, were associated with several patient characteristics, including male sex (hospitalisation hazard ratio [HR] 1·47, 95% CI 1·38-1·57; death HR 1·62, 1·49-1·76) and various comorbidities, with the highest hospitalisation HR found for transplantation (4·53, 1·87-10·98) and the highest death HR for myoneural disease (2·33, 1·46-3·71). For those testing positive, there were decreasing temporal trends in hospitalisation and death rates. The proportion of positive tests among older age groups (>40 years) and those with at-risk comorbidities increased during October, 2020. On Nov 10, 2020, the projected number of hospitalisations for Dec 8, 2020 (28 days later) was 90 per day (95% prediction interval 55-125) and the projected number of deaths was 21 per day (12-29)., Interpretation: The estimated incidence of SARS-CoV-2 infection based on positive tests recorded in this unique data resource has provided forecasts of hospitalisation and death rates for the whole of Scotland. These findings were used by the Scottish Government to inform their response to reduce COVID-19-related morbidity and mortality., Funding: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, UK Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Scottish Government Director General Health and Social Care., Competing Interests: Declaration of interests AS is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group and the New and Emerging Respiratory Virus Threats Risk Stratification Subgroup. CRS declares funding from the Medical Research Council (MRC), National Institute for Health Research (NIHR), Chief Scientist Office, and New Zealand Ministry for Business, Innovation and Employment and Health Research Council, during the conduct of this study. CR reports grants from the MRC and Public Health Scotland, during the conduct of the study, and is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group, Scientific Pandemic Influenza Group on Modelling, Medicines and Healthcare products Regulatory Agency, Vaccine Benefit and Risk Working Group. JM reports grants from EAVE II funded by MRC/NIHR/Scottish Government and grants from IMOVE-COVID-19 funded by WHO (Europe) and the European Centre for Disease Prevention and Control, during the conduct of the study. HRS reports that her institution received grants from the MRC and UK Research and Innovation, during the conduct of the study, and that she received personal fees from Scottish Parliament, outside the submitted work. JLKM reports being the clinical lead of Health Protection for NHS Fife and a member of the COVID-19 National Incident Management Team. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The current pandemic of the 2019 novel coronavirus (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has raised significant public health concern. Rapid, affordable, and accurate diagnostics of SARS-CoV-2 is essential for early treatment and control of the disease spread. In the past few years, CRISPR technology has shown great potential for highly sensitive and specific molecular diagnostics. Amid the ongoing COVID-19 pandemic, there is an increasing interest in implementing CRISPR-based diagnostic principles to develop fast and precise methods for detecting SARS-CoV-2. In this work, we reviewed and summarized these CRISPR-based diagnostic systems as well as their characteristics and challenges. We also provided future perspectives of CRISPR-based sensing towards point-of-care molecular diagnosis applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Outbreaks of SARS-CoV-2 are threatening the health care systems of several countries around the world. The initial control of SARS-CoV-2 epidemics relied on non-pharmaceutical interventions, such as social distancing, teleworking, mouth masks and contact tracing. However, as pre-symptomatic transmission remains an important driver of the epidemic, contact tracing efforts struggle to fully control SARS-CoV-2 epidemics. Therefore, in this work, we investigate to what extent the use of universal testing, i.e., an approach in which we screen the entire population, can be utilized to mitigate this epidemic. To this end, we rely on PCR test pooling of individuals that belong to the same households, to allow for a universal testing procedure that is feasible with the limited testing capacity. We evaluate two isolation strategies: on the one hand pool isolation, where we isolate all individuals that belong to a positive PCR test pool, and on the other hand individual isolation, where we determine which of the individuals that belong to the positive PCR pool are positive, through an additional testing step. We evaluate this universal testing approach in the STRIDE individual-based epidemiological model in the context of the Belgian COVID-19 epidemic. As the organisation of universal testing will be challenging, we discuss the different aspects related to sample extraction and PCR testing, to demonstrate the feasibility of universal testing when a decentralized testing approach is used. We show through simulation, that weekly universal testing is able to control the epidemic, even when many of the contact reductions are relieved. Finally, our model shows that the use of universal testing in combination with stringent contact reductions could be considered as a strategy to eradicate the virus., Competing Interests: The authors have read the journal’s policy concerning competing interests. JV is, besides his employment at the Hasselt University, part of the investment team of Bioqube Ventures. Bioqube Ventures was not involved in this work, nor does it prosper financially as a result of the current study. The other authors declare that they have no competing interests.

Introduction: SARS-Cov-2 first appeared in Wuhan, China, in December 2019 and spread all over the world soon after that. Given the infectious nature ofSARS-CoV-2, fast and accurate diagnosis tools are important to detect the virus. In this review, we discuss the different diagnostic tests that are currently being implemented in laboratories and provide a description of various COVID-19 kits., Areas Covered: We summarize molecular techniques that target the viral load, serological methods used for SARS-CoV-2 specific antibodies detection as well as newly developed faster assays for the detection of SARS-COV 2 in various biological samples., Expert Opinion: In the light of the widespread pandemic, the massive diagnosis of COVID-19, using various detection techniques, appears to be the most effective strategy for monitoring and containing its propagation.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Background and Objectives: Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus disease 2019., Methods: We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts (<18 years), we described transmission, assessed the risk factors for infection, and calculated symptom positive and negative predictive values. We compared secondary infection rates and symptoms between pediatric and adult contacts using generalized estimating equations., Results: Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval [CI]: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio [OR]: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18)., Conclusions: Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

COVID-19 is a disease caused by SARS-CoV-2 capable of causing mild to severe infections in humans. Since its first appearance in China in December 2019, the pandemic has spread rapidly throughout the world. Despite considerable efforts made to contain the disease, the virus has continued its prevalence in many countries with varying degrees of clinical manifestations. To contain this pandemic, collaborative approach involving accurate diagnosis, epidemiology, surveillance, and prophylaxis is essential. However, proper diagnosis using rapid technologies plays a crucial role. With increasing incidence of COVID-19 cases, the accurate and early detection of the SARS-CoV-2 is need of the hour for effective prevention and management of COVID-19 cases as well as to curb its spread. RT-qPCR assay is considered to be the gold standard for the early detection of virus, but this protocol has limited application to use as bedside test because of its technical complexity. To address these challenges, several POC assays have been developed to facilitate the COVID-19 diagnosis outside the centralized testing laboratories as well to accelerate the clinical decision making with a least turnaround time. Hence, in this report, we review different nucleic acid-based and serological techniques available for the diagnosis and effective prevention of COVID-19. KEY POINTS : • Provides comprehensive information on the different diagnostic tools available for COVID-19 • Nucleic acid based tests or antigen detection tests are used for diagnostic purpose • Accurate diagnosis is essential for the efficient management of COVID-19.

Objective: COVID-19 has affected surgical practice globally. Treating neurosurgical patients with the restrictions imposed by the pandemic is challenging in institutions with shared patient areas. The present study was performed to assess the changing patterns of neurosurgical cases, the efficacy of repeated testing before surgery, and the prevalence of COVID-19 in asymptomatic neurosurgical inpatients., Methods: Cases of non-trauma-related neurosurgical patients treated at the Postgraduate Institute of Medical Education and Research (PGIMER) before and during the COVID-19 pandemic were reviewed. During the pandemic, all patients underwent a nasopharyngeal swab reverse transcription-polymerase chain reaction test to detect COVID-19 at admission. Patients who needed immediate intervention were surgically treated following a single COVID-19 test, while stable patients who initially tested negative for COVID-19 were subjected to repeated testing at least 5 days after the first test and within 48 hours prior to the planned surgery. The COVID-19 positivity rate was compared with the local period prevalence. The number of patients who tested positive at the second test, following a negative first test, was used to determine the probable number of people who could have become infected during the surgical procedure without second testing., Results: Of the total 1769 non-trauma-related neurosurgical patients included in this study, a mean of 337.2 patients underwent surgery per month before COVID-19, while a mean of 184.2 patients (54.6% of pre-COVID-19 capacity) underwent surgery per month during the pandemic period, when COVID-19 cases were on the rise in India. There was a significant increase in the proportion of patients undergoing surgery for a ruptured aneurysm, stroke, hydrocephalus, and cerebellar tumors, while the number of patients seeking surgery for chronic benign diseases declined. At the first COVID-19 test, 4 patients (0.48%) tested were found to have the disease, a proportion 3.7 times greater than that found in the local community. An additional 5 patients tested positive at the time of the second COVID-19 test, resulting in an overall inpatient period prevalence of 1%, in contrast to a 0.2% national cumulative caseload. It is possible that COVID-19 was prevented in approximately 67.4 people every month by using double testing., Conclusions: COVID-19 has changed the pattern of neurosurgical procedures, with acute cases dominating the practice. Despite the fact that the pandemic has not yet reached its peak in India, COVID-19 has been detected 3.7 times more often in asymptomatic neurosurgical inpatients than in the local community, even with single testing. Double testing displays an incremental value by disclosing COVID-19 overall in 1 in 100 inpatients and thus averting its spread through neurosurgical services.