Comparison between Nasal and Nasopharyngeal Swabs for SARS-CoV-2 Rapid Antigen Detection in an Asymptomatic Population, and Direct Confirmation by RT-PCR from the Residual Buffer.

Containment measures employed during the COVID-19 pandemic included prompt recognition of cases, isolation, and contact tracing. Bilateral nasal (NA) swabs applied to a commercial antigen-based rapid diagnostic test (Ag-RDT) offer a simpler and more comfortable alternative to nasopharyngeal (NP) collection; however, little is known about the sensitivity of this method in an asymptomatic population. Participants in community-based asymptomatic testing sites were screened for SARS-CoV-2 using an Ag-RDT with NP sampling. Positive individuals returned for confirmatory molecular testing and consented to repeating the Ag-RDT using a bilateral NA swab for comparison. Residual test buffer (RTB) from Ag-RDTs was subjected to real-time reverse transcription-PCR (RT-PCR). Of 123,617 asymptomatic individuals, 197 NP Ag-RDT-positive participants were included, with 175 confirmed positive by RT-PCR. Of these cases, 154 were identified from the NA swab collection with Ag-RDT, with a sensitivity of 88.0% compared to the NP swab collection. Stratifying results by RT-PCR cycle threshold demonstrated that sensitivity of the nasal collection method varied based on the cycle threshold (CT) value of the paired RT-PCR sample. RT-PCR testing on the RTB from the Ag-RDT using NP and NA swab collections resulted in 100.0% and 98.7% sensitivity, respectively. NA swabs provide an adequate alternative to NP swab collection for use with Ag-RDT, with the recognition that the test is most sensitive in specimens with high viral loads. With the high sensitivity of RT-PCR testing on RTB from Ag-RDT, a more streamlined approach to confirmatory testing is possible without recollection or use of paired collections strategies. IMPORTANCE Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type.

Asymptomatic carriage and transmission of SARS-CoV-2: What do we know?

PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.

RéSUMé: OBJECTIF: Le risque encouru par les travailleurs de la santé traitant des patients asymptomatiques infectés par le syndrome respiratoire aigu sévère du coronavirus 2 (SARS-CoV-2) en salle d'opération dépend de plusieurs facteurs. Ce compte rendu examine les données probantes concernant la présence asymptomatique ou pré-symptomatique du SARS-CoV-2, le risque de transmission des patients asymptomatiques, et les risques spécifiques associés aux interventions générant des aérosols. Nous passons également en revue différentes mesures de protection, telles que la minimisation des aérosols et l'utilisation d'équipements de protection individuelle, dans un contexte de traitement de patients asymptomatiques. SOURCE: Nous avons examiné la littérature publiée ainsi que les directives sociétales. CONSTATATIONS PRINCIPALES: Selon certaines données probantes, une proportion des personnes infectées par le SARS-CoV-2 possèdent des charges virales détectables avant la présence de symptômes, voire même sans manifestation de symptômes. Le degré de risque de transmission des patients asymptomatiques aux travailleurs de la santé dépendra de la prévalence de la maladie dans la population, une donnée difficile à évaluer sans dépistage généralisé. Les interventions générant des aérosols augmentent le risque de transmission virale des patients symptomatiques infectés aux travailleurs de la santé, mais la transmission de patients asymptomatiques n'a pas été rapportée. Les techniques visant à minimiser l'aérosolisation et les équipements de protection individuelle adaptés pourraient être utiles pour réduire le risque des travailleurs de la santé en salle d'opération. Certaines directives régionales et nationales recommandent le recours à des précautions contre la transmission par voie aérienne durant les interventions générant des aérosols pratiquées sur des patients asymptomatiques pendant la pandémie de coronavirus, bien que les données probantes appuyant cette pratique soient limitées. CONCLUSION: La transmission virale des patients asymptomatiques en salle d'opération est plausible et les efforts visant à réduire le risque pour les travailleurs de la santé comprennent la réduction de l'aérosolisation et le port d'équipements de protection individuelle adaptés, deux mesures dont la faisabilité variera en fonction du risque géographique et de la disponibilité des équipements.

Clinical evaluation of the SD Biosensor SARS-CoV-2 saliva antigen rapid test with symptomatic and asymptomatic, non-hospitalized patients.

BACKGROUND: Performance of the SD Biosensor saliva antigen rapid test was evaluated at a large designated testing site in non-hospitalized patients, with or without symptoms. METHOD: All eligible people over 18 years of age presenting for a booked appointment at the designated SARS-CoV-2 testing site were approached for inclusion and enrolled following verbal informed consent. One nasopharyngeal swab was taken to carry out the default antigen rapid test from which the results were reported back to the patient and one saliva sample was self-taken according to verbal instruction on site. This was used for the saliva antigen rapid test, the RT-PCR and for virus culture. Sensitivity of the saliva antigen rapid test was analyzed in two ways: i, compared to saliva RT-PCR; and ii, compared to virus culture of the saliva samples. Study participants were also asked to fill in a short questionnaire stating age, sex, date of symptom onset. Recommended time of ≥30mins since last meal, drink or cigarette if applicable was also recorded. The study was carried out in February-March 2021 for 4 weeks. RESULTS: We could include 789 people with complete records and results. Compared to saliva RT-PCR, overall sensitivity and specificity of the saliva antigen rapid test was 66.1% and 99.6% which increased to 88.6% with Ct ≤30 cutoff. Analysis by days post onset did not result in higher sensitivities because the large majority of people were in the very early phase of disease ie <3 days post onset. When breaking down the data for symptomatic and asymptomatic individuals, sensitivity ranged from 69.2% to 50% respectively, however the total number of RT-PCR positive asymptomatic participants was very low (n = 5). Importantly, almost all culture positive samples were detected by the rapid test. CONCLUSION: Overall, the potential benefits of saliva antigen rapid test, could outweigh the lower sensitivity compared to nasopharyngeal antigen rapid test in a comprehensive testing strategy, especially for home/self-testing and in vulnerable populations like elderly, disabled or children where in intrusive testing is either not possible or causes unnecessary stress.

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms.

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS).

BACKGROUND: There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2. METHODS AND FINDINGS: We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status. CONCLUSIONS: We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.

Ct Values Do Not Predict Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmissibility in College Students.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation, and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected individuals affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We examined whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the non-spreaders in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than that in the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus, Ct value, or the viral load, at the individual level could not predict the transmissibility. Instead, a sensitive method to detect the presence of virus is needed to identify asymptomatic individuals who may carry a low viral load but can still be infectious.

Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2.

During the current SARS-CoV-2 pandemic new studies are emerging daily providing novel information about sources, transmission risks and possible prevention measures. In this review, we aimed to comprehensively summarize the current evidence on possible sources for SARS-CoV-2, including evaluation of transmission risks and effectiveness of applied prevention measures. Next to symptomatic patients, asymptomatic or pre-symptomatic carriers are a possible source with respiratory secretions as the most likely cause for viral transmission. Air and inanimate surfaces may be sources; however, viral RNA has been inconsistently detected. Similarly, even though SARS-CoV-2 RNA has been detected on or in personal protective equipment (PPE), blood, urine, eyes, the gastrointestinal tract and pets, these sources are currently thought to play a negligible role for transmission. Finally, various prevention measures such as handwashing, hand disinfection, face masks, gloves, surface disinfection or physical distancing for the healthcare setting and in public are analysed for their expected protective effect.

Prediction of False-Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Molecular Results in a High-Throughput Open-Platform System.

Widespread high-throughput testing for identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR has been a foundation in the response to the coronavirus disease 2019 (COVID-19) pandemic. Quality assurance metrics for these RT-PCR tests are still evolving as testing is widely implemented. As testing increases, it is important to understand performance characteristics and the errors associated with these tests. Herein, we investigate a high-throughput, laboratory-developed SARS-CoV-2 RT-PCR assay to determine whether modeling can generate quality control metrics that identify false-positive (FP) results due to contamination. This study reviewed repeated clinical samples focusing on positive samples that test negative on re-extraction and PCR, likely representing false positives. To identify and predict false-positive samples, we constructed machine learning-derived models based on the extraction method used. These models identified variables associated with false-positive results across all methods, with sensitivities for predicting FP results ranging between 67% and 100%. Application of the models to all results predicted a total FP rate of 0.08% across all samples, or 2.3% of positive results, similar to reports for other RT-PCR tests for RNA viruses. These models can predict quality control parameters, enabling laboratories to generate decision trees that reduce interpretation errors, allow for automated reflex testing of samples with a high FP probability, improve workflow efficiency, and increase diagnostic accuracy for patient care.

Evaluating Diagnostic Accuracy of Saliva Sampling Methods for Severe Acute Respiratory Syndrome Coronavirus 2 Reveals Differential Sensitivity and Association with Viral Load.

Nasopharyngeal swabs are considered the preferential collection method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Less invasive and simpler alternative sampling procedures, such as saliva collection, are desirable. We compared saliva specimens and nasopharyngeal (NP) swabs with respect to sensitivity in detecting SARS-CoV-2. A nasopharyngeal and two saliva specimens (collected by spitting or oral swabbing) were obtained from >2500 individuals. All samples were tested by RT-qPCR, detecting RNA of SARS-CoV-2. The test sensitivity was compared on the two saliva collections with the nasopharyngeal specimen for all subjects and stratified by symptom status and viral load. Of the 2850 patients for whom all three samples were available, 105 were positive on NP swab, whereas 32 and 23 were also positive on saliva spitting and saliva swabbing samples, respectively. The sensitivity of the RT-qPCR to detect SARS-CoV-2 among NP-positive patients was 30.5% (95% CI, 1.9%-40.2%) for saliva spitting and 21.9% (95% CI, 14.4%-31.0%) for saliva swabbing. However, when focusing on subjects with medium to high viral load, sensitivity on saliva increased substantially: 93.9% (95% CI, 79.8%-99.3%) and 76.9% (95% CI, 56.4%-91.0%) for spitting and swabbing, respectively, regardless of symptomatic status. Our results suggest that saliva cannot readily replace nasopharyngeal sampling for SARS-CoV-2 diagnostics but may enable identification of the most contagious cases with medium to high viral loads.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients.

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis.

BACKGROUND: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. METHODS AND FINDINGS: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting. CONCLUSIONS: In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters.

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature.

Analysis of COVID-19 pandemics in Kazakhstan.

BACKGROUND: This study aimed to analyze the demographic and epidemiological features of identified COVID-19 cases in Kazakhstan. STUDY DESIGN: A cross-sectional study. METHODS: This cross-sectional study aimed to analyze COVID-19 cases (n=5116) collected from March 13 to June 6, 2020, in Kazakhstan. The data were obtained from a state official medical electronic database. The study investigated the geographic and demographic data of patients as well as the association of COVID-19 cases with gender and age. The prevalence of symptoms, the presence of comorbidities, complications, and COVID-19 mortality were determined for all patients. RESULTS: The mean±SD age of the patients in this study was 34.8±17.6 years, and the majority (55.7%) of COVID-19 cases were male and residents of cities (79.6%). In total, 80% of the cases had the asymptomatic/mild form of the disease. Cough (20.8 %) and sore throat (17.1%) were the most common symptoms among patients, and pneumonia was diagnosed in 1 out of 5 cases. Acute respiratory distress syndrome (ARDS) was recorded in 1.2% of the patients. The fatality rate was 1% in the study population and lethality was 2.6 times higher in males compared to females.  Each additional year in age increased the probability of COVID-19 infection by 1.06 times. The presence of cardiovascular, diabetes, respiratory, and kidney diseases affected the rate of mortality (P<0.05). CONCLUSION: The results demonstrated a high proportion (40%) of the asymptomatic type of coronavirus infection in the Kazakhstan population. The severity of COVID-19 symptoms and lethality were directly related to the age of patients and the presence of comorbidities.

Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study.

OBJECTIVE: To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. DESIGN: Observational cohort study. SETTING: Community LFT pilot at covid-19 testing sites in Liverpool, UK. PARTICIPANTS: 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. INTERVENTIONS: Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. RESULTS: Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >106 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>104 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<104 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. CONCLUSIONS: The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.