scholarly journals Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant

Author(s):  
James A Hay ◽  
Stephen M Kissler ◽  
Joseph R Fauver ◽  
Christina Mack ◽  
Caroline G Tai ◽  
...  

Background. The Omicron SARS-CoV-2 variant is responsible for a major wave of COVID-19, with record case counts reflecting high transmissibility and escape from prior immunity. Defining the time course of Omicron viral proliferation and clearance is crucial to inform isolation protocols aiming to minimize disease spread. Methods. We obtained longitudinal, quantitative RT-qPCR test results using combined anterior nares and oropharyngeal samples (n = 10,324) collected between July 5th, 2021 and January 10th, 2022 from the National Basketball Association's (NBA) occupational health program. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30, chosen as a proxy for potential infectivity and antigen test positivity, on each day after first detection of suspected and confirmed Omicron infections, stratified by individuals detected under frequent testing protocols and those detected due to symptom onset or concern for contact with an infected individual. We quantified the duration of viral proliferation, clearance rate, and peak viral concentration for individuals with acute Omicron and Delta variant SARS-CoV-2 infections. Results. A total of 97 infections were confirmed or suspected to be from the Omicron variant and 107 from the Delta variant. Of 27 Omicron-infected individuals testing positive ≤1 day after a previous negative or inconclusive test, 52.0% (13/25) were PCR positive with Ct values <30 at day 5, 25.0% (6/24) at day 6, and 13.0% (3/23) on day 7 post detection. Of 70 Omicron-infected individuals detected ≥2 days after a previous negative or inconclusive test, 39.1% (25/64) were PCR positive with Ct values <30 at day 5, 33.3% (21/63) at day 6, and 22.2% (14/63) on day 7 post detection. Overall, Omicron infections featured a mean duration of 9.87 days (95% CI 8.83-10.9) relative to 10.9 days (95% CI 9.41-12.4) for Delta infections. The peak viral RNA based on Ct values was lower for Omicron infections than for Delta infections (Ct 23.3, 95% CI 22.4-24.3 for Omicron; Ct 20.5, 95% CI 19.2-21.8 for Delta) and the clearance phase was shorter for Omicron infections (5.35 days, 95% CI 4.78-6.00 for Omicron; 6.23 days, 95% CI 5.43-7.17 for Delta), though the rate of clearance was similar (3.13 Ct/day, 95% CI 2.75-3.54 for Omicron; 3.15 Ct/day, 95% CI 2.69-3.64 for Delta). Conclusions. While Omicron infections feature lower peak viral RNA and a shorter clearance phase than Delta infections on average, it is unclear to what extent these differences are attributable to more immunity in this largely vaccinated population or intrinsic characteristics of the Omicron variant. Further, these results suggest that Omicron's infectiousness may not be explained by higher viral load measured in the nose and mouth by RT-PCR. The substantial fraction of individuals with Ct values <30 at days 5 of infection, particularly in those detected due to symptom onset or concern for contact with an infected individual, underscores the heterogeneity of the infectious period, with implications for isolation policies.

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Sandra A Springer ◽  
Silvina Masciotra ◽  
Jeffrey A Johnson ◽  
Sheldon Campbell

Abstract We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management.


Author(s):  
Selina Natalia ◽  
Felicia Imanuella Thorion ◽  
Luky Adlino ◽  
Clifford Eltin John ◽  
Andree Kurniawan ◽  
...  

Objective : Coronavirus disease 2019 (COVID-19) has been declared as an international public health emergency by the World Health Organization (WHO), with outbreaks in over 200 countries and causing over 390,000 deaths globally. ACE-2 receptors are highly expressed in the upper and lower gastrointestinal system, providing a prerequisite for SARS-CoV-2 infection in the gastrointestinal tract. In addition, over half of the COVID-19 patients have viral nucleic acid detected in their feces and almost one-quarter of the cases, the stool samples test positive even when respiratory samples are negative. The aim of this systematic review is to summarize literature and to evaluate the clinical characteristics of patients with positive viral RNA stool test for COVID-19 and if there is a possibility of fecal-oral transmission of SARS-CoV-2 virus.Method : This systematic review has been registered in PROSPERO (CRD42020183049). A systematic search of the literature for observational study and randomized control trial was conducted in PubMed central and Google Scholar through May 5th, 2020. Three reviewers independently searched and selected. The risk of bias was evaluated using Newcastle-Ottawa Quality assessment tool.Results : 340 articles were screened, then from which eight articles were selected. Of eight articles that were included in this study, we sought for three main categories of the clinical manifestation; gastrointestinal, respiratory, and others. Each study was reviewed systematically to gain demographic data and evidence regarding the possibility of fecal oral transmission in SARS-CoV-2. Two studies reported prolongation of positive stool test results after the respiratory specimen conversion to negative which support the theory of fecal oral transmission.Conclusion : In conclusion, diarrhea, cough, and fever are the most common clinical manifestations in COVID-19 patients with positive RNA stool test results. Fecal oral transmission may be possible due to the ACE-2 receptors in the lining of the gastrointestinal tract. RNA stool test should be used as addition in discharging COVID-19 patients.


2021 ◽  
Author(s):  
Toshihito Nomura ◽  
Hiroki Kitagawa ◽  
Keitaro Omori ◽  
Norifumi Shigemoto ◽  
Masaki Kakimoto ◽  
...  

Abstract Approximately 5% of patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 develop severe COVID-19. Severe COVID-19 requires respiratory management with mechanical ventilation and an extended period of treatment. Prolonged infectious virus shedding is a concern in severe COVID-19 cases, but few reports have examined the duration of infectious virus shedding. Therefore, we investigated the duration of infectious virus shedding in patients transferred to Hiroshima University Hospital with severe COVID-19 requiring mechanical ventilation. Nasopharyngeal swab specimens were collected and analyzed using both viral culture and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) tests between December 2020 and February 2021. Of the 23 patients tested, the proportions of those with positive test results at first specimen collection on RT-qPCR and viral culture tests were 95·7% and 30·4%, respectively. All six patients with positive viral culture test results who were followed-up tested negative 24 days after symptom onset but remained positive on RT-qPCR. The longest negative conversion time was observed in a dialysis patient on immunosuppressive drugs. This study indicated that patients with severe COVID-19 remain culture positive for ≥ 10 days after symptom onset. Additionally, immunosuppressed patients with severe COVID-19 could consider isolation for ≥ 20 days.


Author(s):  
Razvan G. Romanescu ◽  
Rob Deardon

Abstract Properties of statistical alarms have been well studied for simple disease surveillance models, such as normally distributed incidence rates with a sudden or gradual shift in mean at the start of an outbreak. It is known, however, that outbreak dynamics in human populations depend significantly on the heterogeneity of the underlying contact network. The rate of change in incidence for a disease such as influenza peaks early on during the outbreak, when the most highly connected individuals get infected, and declines as the average number of connections in the remaining susceptible population drops. Alarm systems currently in use for detecting the start of influenza seasons generally ignore this mechanism of disease spread, and, as a result, will miss out on some early warning signals. We investigate the performance of various alarms on epidemics simulated from an undirected network model with a power law degree distribution for a pathogen with a relatively short infectious period. We propose simple custom alarms for the disease system considered, and show that they can detect a change in the process sooner than some traditional alarms. Finally, we test our methods on observed rates of influenza-like illness from two sentinel providers (one French, one Spanish) to illustrate their use in the early detection of the flu season.


2007 ◽  
Vol 19 (5) ◽  
pp. 459-464
Author(s):  
H. Jane Oakey

Degradation of RNA in diagnostic specimens can cause false-negative test results and potential misdiagnosis when tests rely on the detection of specific RNA sequence. Current molecular methods of checking RNA integrity tend to be host species or group specific, necessitating libraries of primers and reaction conditions. The objective here was to develop a universal (multi-species) quality assurance tool for determining the integrity of RNA in animal tissues submitted to a laboratory for analyses. Ribosomal RNA (16S rRNA) transcribed from the mitochondrial 16S rDNA was used as template material for reverse transcription to cDNA and was amplified using polymerase chain reaction (PCR). As mitochondrial DNA has a high level of conservation, the primers used were shown to reverse transcribe and amplify RNA from every animal species tested. Deliberate degradation of rRNA template through temperature abuse of samples resulted in no reverse transcription and amplification. Samples spiked with viruses showed that single-stranded viral RNA and rRNA in the same sample degraded at similar rates, hence reverse transcription and PCR amplification of 16S rRNA could be used as a test of sample integrity and suitability for analysis that required the sample's RNA, including viral RNA. This test will be an invaluable quality assurance tool for determination of RNA integrity from tissue samples, thus avoiding erroneous test results that might occur if degraded target RNA is used unknowingly as template material for reverse transcription and subsequent PCR amplification.


2005 ◽  
Vol 3 (1) ◽  
pp. nrs.03002 ◽  
Author(s):  
Xiaohui Yuan ◽  
Barry Marc Forman

Illicit use of performance-enhancing steroids has proliferated among a wide range of professional and amateur athletes. This problem has attracted broad public attention and has led the United States Congress to draft legislation that proposes frequent testing of athletes. However, current testing protocols are inadequate as athletes can evade detection by using novel steroids that are unknown to authorities. We have developed a strategy that overcomes this limitation by virtue of its ability to detect “designer steroids” without prior knowledge of their existence.


2013 ◽  
Vol 103 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Tito Caffi ◽  
Giovanna Gilardi ◽  
Matteo Monchiero ◽  
Vittorio Rossi

To study the influence of environmental conditions on sporulation of Plasmopara viticola lesions under vineyard's conditions, unsprayed vines were inspected every second or third day and the numbers of sporulating and nonsporulating lesions were counted in two North Italy vineyards in 2008 to 2010. Infected leaves were removed so that only fresh lesions were assessed at each field assessment. Sporulation was studied at two scales, across field assessments and across the seasonal population of lesions. Frequencies of sporulating lesions were positively correlated with the numbers of moist hours in the preceding dark period (i.e., the number of hours between 8:00 p.m. and 7:00 a.m. with relative humidity ≥80%, rainfall >0 mm, or wetness duration >30 min). In a receiver operating characteristic analysis, predicted sporulation based on the occurrence of ≥3 moist hours at night provided overall accuracy of 0.85. To study the time course of sporulation on lesions which were not washed by rainfall, numbers of sporangia produced per square millimeter of lesion were estimated on individual cohorts of lesions over the whole infectious period. The numbers of sporangia per square millimeter of lesion increased rapidly during the first 4 days after the beginning of sporulation and then tapered off prior to a halt; the time course of cumulative sporangia production by a lesion followed a monomolecular growth model (R2 = 0.97). The total number of sporangia produced by a square millimeter of lesion increased as the maximum temperature decreased and moist hours in the dark increased. To study the release pattern of the sporangia, spore samplers were placed near grapevines with sporulating lesions. Airborne sporangia were caught in 91.2% of the days over a wide range of weather conditions, including rainless periods. The results of this study provide quantitative information on production of P. viticola sporangia that may help refine epidemiological models used as decision aids in grape disease management programs.


2011 ◽  
Vol 26 (S1) ◽  
pp. s51-s51
Author(s):  
G.M. Hwang ◽  
T. Wilson

With increasing numbers of international flights and air travelers arriving in the US annually, the rapid spread of communicable diseases has grown. Epidemics of novel infectious diseases have emerged and rapidly spread globally in association with air travel, including the severe acute respiratory syndrome (SARS) outbreak in 2003 and H1N1 in 2009. In order to anticipate and mitigate the consequences of future rapid disease spread, the MITRE Corporation, in collaboration with the (US) Centers for Disease Control and Prevention, developed a risk assessment tool using a Susceptible-Exposed-Infectious-Recovered model and detailed flight and population data. The emergence and spread of prototypic pandemic influenza was simulated based on a theoretical geographical point of origin and its communicability. More than 50 international metropolitan areas were analyzed as potential points of origin to simulate the rapidity of spread to the US. The basic reproduction number (Ro), defined as the average number of persons to whom one infected individual transmits disease in an immune naive population, was varied from 1.4 to 1.9. The starting numbers of infectious persons at each origin also were varied (100 or 500 persons, 5% infectious may travel). Waves were computed as aggregate across metropolitan areas modeled in the US. The visualization of the first pandemic wave was most apparent in simulations of Ro = 1.9, resulting from 500 infectious persons at each origin. More than 50% of origins indicated that aggregate waves peaked around Day 125, while 30% of origins peaked around Day 90. Additionally, the time, in days, from its origin in six continents into the US was compared, and a two-week delay was found from South America compared with other continents. This simulation tool better equips policy makers and public health officials to quickly assess risk and leverage resources efficiently via targeted and scalable border mitigation measures during a rapid global outbreak.


Author(s):  
Jianping Huang ◽  
Tingting Mao ◽  
Shufei Li ◽  
Lianpeng Wu ◽  
Xueqin Xu ◽  
...  

ABSTRACTOBJECTIVETo investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period.DESIGNRetrospective, observational case series.SETTINGWenzhou Sixth People’s HospitalPARTICIPANTSThirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020.MAIN OUTCOME MEASURESThroat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed.RESULTSAt the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients.CONCLUSIONThis study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.WHAT IS ALREADY KNOWN ON THIS TOPICThere are several reports about the serum antibodies against SARS-CoV-2. However, most of them evaluate diagnostic accuracy. Only two articles report dynamics of SARS-CoV-2 viral RNA and antibodies with serial samples, but the observation periods are within 30 days. None of the studies investigate the profiles of SARS-CoV-2 viral load and antibodies in a long period. Three reports investigate profiles in respiratory samples, but there are no reports on the dynamics of the viral load in stool samples.WHAT THIS STUDY ADDSIn both sputum and stool, SARS-CoV-2 RNA persists for a long time. The anti-RBD antibodies may involve in the clearance of SARS-CoV-2 infection. After eight weeks from symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels increased 4-time higher in convalescence than in acute phase. Long persistence of SARS-CoV-2 viral RNA in sputum and stool presents challenges for management of the infection. The IgM/IgG comb test is better than single IgM test as a supplement diagnostic tool. Anti-RBD may be a protective antibody, and is valuable for development of vaccines.


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