scholarly journals Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in a longitudinally sampled cohort of COVID-19 outpatients

2021 ◽  
Author(s):  
Annukka A R Antar ◽  
Tong Yu ◽  
Nora Pisanic ◽  
Razvan Azamfirei ◽  
Jeffrey A Tornheim ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Oral Fluid ◽  
Gingival Crevicular Fluid ◽  
Rna Virus ◽  
Cox Proportional Hazards ◽  
Viral Rna ◽  
Antibody Detection ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Virus Culture

Abstract Background Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. Methods Ninety-five symptomatic outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. Results Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). Conclusions We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

scholarly journals Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

2021 ◽  
Author(s):  
Annukka A. R. Antar ◽  
Tong Yu ◽  
Nora Pisanic ◽  
Razvan Azamfirei ◽  
Jeffrey A. Tornheim ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Oral Fluid ◽  
Gingival Crevicular Fluid ◽  
Rna Virus ◽  
Cox Proportional Hazards ◽  
Viral Rna ◽  
Antibody Detection ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Virus Culture

ABSTRACTBackgroundSustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.MethodsNinety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.ResultsViral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044).ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

scholarly journals SARS-CoV-2 RNA and antibody dynamics in a Dutch household study with dense sampling frame

2021 ◽  
Author(s):  
Wanda G.H. Han ◽  
Arno Swart ◽  
Axel Bonacic Marinovic ◽  
Dirk Eggink ◽  
Johan Reimerink ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Symptom Severity ◽  
Oral Fluid ◽  
Probability Of Detection ◽  
Serological Response ◽  
Sample Type ◽  
Sampling Frame ◽  
Rt Pcr ◽  
Specific Antibodies ◽  
Viral Loads

AbstractThis study investigated the dynamics of SARS-CoV-2 infection and diagnostics in household members of different ages and with different symptom severity after SARS-CoV-2 exposure during the early phase of the pandemic. Households with a SARS-CoV-2 confirmed positive case and at least one child in the Netherlands were followed for 6 weeks. Naso (NP)- and oropharyngeal (OP) swabs, oral fluid and feces specimens were analyzed for SARS-CoV-2 RNA and serum for SARS-CoV-2-specific antibodies. The dynamics of the presence of viral RNA and the serological response was modeled to determine the sampling time-frame and sample type with the highest sensitivity to confirm or reject a SARS-CoV-2 diagnosis. Transmission of SARS-CoV-2 between adults and children within a household was correlated with symptom severity of index cases. In children higher viral loads compared to adults were detected at symptom onset. Early in infection, higher viral loads were detected in NP and OP specimens, while RNA in especially feces were longer detectable. SARS-CoV-2-specific antibodies have a 90% probability of detection from 7 days (total Ig) and 18 days (IgG) since symptom onset. In conclusion this study has shown that on average, children carry higher loads of virus as compared to adults early after infection. For highest probability of detection in SARS-CoV-2 diagnostics early in infection, RT-PCR on NP and OP specimens are more sensitive than on oral fluid and feces. For SARS-CoV-2 diagnostics late after infection, RT-PCR on feces specimens and serology are more valuable.

scholarly journals At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sue Mallett ◽  
A. Joy Allen ◽  
Sara Graziadio ◽  
Stuart A. Taylor ◽  
Naomi S. Sakai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Virus Detection ◽  
Risk Of Bias ◽  
Individual Participant Data ◽  
Upper Respiratory Tract ◽  
Test Results ◽  
Rt Pcr ◽  
Individual Participant

Abstract Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Results Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Conclusions RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.

scholarly journals Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infectiousness: A Cohort Study of Individuals With COVID-19

2021 ◽  
Author(s):  
Daniel Owusu ◽  
Mary A Pomeroy ◽  
Nathaniel M Lewis ◽  
Ashutosh Wadhwa ◽  
Anna R Yousaf ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Viral Rna ◽  
Cox Proportional Hazards Regression ◽  
Viral Culture ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Participant Characteristics ◽  
Pcr Test

Abstract Background To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset. Methods We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR–confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset. Results The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6–5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3–.9) compared to participants aged 18–49 years. No replication-competent viruses were recovered. Conclusions Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.

scholarly journals SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis

2020 ◽  
Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Grey Literature ◽  
Viral Rna ◽  
Viral Dynamics ◽  
Upper Respiratory Tract ◽  
Live Virus ◽  
Viral Shedding ◽  
Upper Respiratory

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.

scholarly journals Repeat testing for SARS-COV-2: Persistence of viral RNA is common, and clearance is slower in older age groups

2020 ◽  
Author(s):  
Paulina Stehlik ◽  
Kylie Alcorn ◽  
Anna Jones ◽  
Sanmarié Schlebusch ◽  
Andre Wattiaux ◽  
...  
Keyword(s):  
Median Time ◽  
Cox Regression ◽  
Viral Clearance ◽  
Viral Rna ◽  
Published Data ◽  
List Type ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Clearance Rates ◽  
Repeat Testing

ABSTRACTOBJECTIVEThe Novel Coronavirus, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suppression program has been relatively successful in Queensland, Australia. Initially, it involved extensive community testing and repeat sampling of positive individuals for release from isolation. This enabled study of several characteristics, including persistence of detectable virus and how apparent viral clearance rates varied by age and sex.DESIGNWe conducted an exploratory analysis of Queensland Pathology SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) test results. Kaplan Meier analyses were used to estimate median time to apparent viral clearance, and Cox regression to explore the effects of sex and age.SETTING AND PARTICIPANTSIndividuals tested for presence of SARS-CoV-2 in the upper respiratory tract between January 19 and June 4, 2020.OUTCOME MEASURESPresence of viral RNA detected by RT-PCR.RESULTSWe analysed 97,476 individuals. Median age was 41y (range <1-105y), and 57.2% (95% CI 57.2, 57.2) were female. In total, 958 (0.98%; 95% CI 0.92,1.05) tested positive for SARS-CoV-2. Positivity rates were lower in regional areas than cities, in females (OR 0.80, 95% CI 0.70, 0.91), and in those aged 16y and below (p<0.01, test for trend).Of the 958 positive individuals, 243 had two or more (maximum 17) additional tests, and 92% (95% CI 88.1, 95.2) remained positive after 10 days (maximum 72 days) after the initial result.Median time to apparent viral clearance was longer in those 65y and over compared to those under 65y (29 v 43 days, HR 1.85; 95% CI 1.17, 2.90), and was unaffected by sex (HR 0.93; 95% CI 0.66, 1.30).CONCLUSIONSFemales and those 16y and under were less likely to test positive for SARS-CoV-2. Detectable RNA may persist for long periods, negating the value of repeat testing for declaring individuals free of infection. Viral clearance rates appear lower in those over 65y of age compared with younger individuals.“The known”-Early in the COVID-19 pandemic, 2 negative RT-PCR swabs were used to achieve negative status in infected individuals-There are few published data on the patterns of results seen with repeat testing.“The new”-We analysed data from a large cohort of people tested for viral RNA in Queensland, Australia.-We found that females and those 16 y and under were less likely to test positive.-Viral RNA was detectable for up to 72 days, with >90% testing positive for more than 10 days.-Viral clearance was slower in those over the age of 65.“The implications”-Our findings support that there is likely to be little value in repeat RT-PCR testing to declare individuals free from infection.

scholarly journals 513. Viral kinetics of SARS-CoV-2 in patients with COVID-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S322-S323
Author(s):  
Da Young Kim ◽  
Ju-Hyung Lee ◽  
Hyeon Jeong Oh ◽  
Jun-won Seo ◽  
Na Ra Yun ◽  
...  
Keyword(s):  
Chest Radiograph ◽  
Symptom Onset ◽  
Supplemental Oxygen ◽  
University Hospital ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Viral Kinetics ◽  
Viral Loads ◽  
Severe Group ◽  
Kinetics Of

Abstract Background As only few studies have analyzed viral kinetics between the incubation and symptomatic periods of COVID-19 patients, we investigated the viral kinetics and compared viral loads between patients with mild and severe COVID-19. Methods We determined the viral kinetics of 10 patients diagnosed with COVID-19 at Chosun University Hospital. Six patients were classified into the “mild” group and 4 into the “severe” group according to supplemental oxygen use during admission. Samples were collected via nasopharyngeal swabs and sputum specimens. SARS-CoV-2 was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Chest radiograph scores during hospitalization were obtained Results Ct values of the upper respiratory tract specimens were low during the early stages after symptom onset but gradually increased over time in both groups. The severe group had lower Ct values than the mild group. The Ct values of the RdRP and E genes on day 6 after symptom onset were significantly lower in the severe group than in the mild group (p &lt; 0.05). Three of 6 patients had positive results on RT-PCR even before symptom onset; 2 of them had the lowest Ct values. The chest radiograph scores were higher in the severe group than in the mild group, and the score in the severe group was the highest at approximately 3 weeks after symptom onset. Ct values when the RdRP gene and E gene were targeted to detect SARS-CoV-2 on the basis of the days after symptom onset in all the patients Conclusion Viral load and chest radiograph scores were significantly different between the severe and mild groups of COVID-19 patients. Disclosures All Authors: No reported disclosures

scholarly journals Self-collected oral fluid saliva is insensitive compared to nasal-oropharyngeal swabs in the detection of SARS-CoV-2 in outpatients

2020 ◽  
Author(s):  
Yukari C Manabe ◽  
Carolyn Reuland ◽  
Tong Yu ◽  
Razvan Azamfirei ◽  
Justin P Hardick ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Oral Fluid ◽  
Gingival Crevicular Fluid ◽  
Fluid Collection ◽  
Nasopharyngeal Swab ◽  
Multiple Time ◽  
Multiple Time Points ◽  
Widespread Access ◽  
Crevicular Fluid ◽  
Positive Agreement

Abstract SARS-CoV-2 pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared to the nasopharyngeal swab. We compared rRT-PCR Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a non-hospitalized, ambulatory cohort of COVID-19 patients at multiple time points. There were 171 matched specimen pairs. Compared to nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid collection device increased the percent positive agreement from 37.2% (16/43) to 44.6% (29/65). The percent positive agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample. In this study of non-hospitalized SARS-CoV-2 infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared to nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection, and the time from symptom onset especially in outpatient populations.

scholarly journals At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR based tests?: A systematic review of individual participant data

2020 ◽  
Author(s):  
Sue Mallett ◽  
Joy Allen ◽  
Sara Graziadio ◽  
Stuart A Taylor ◽  
Naomi S Sakai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Virus Detection ◽  
Risk Of Bias ◽  
Individual Participant Data ◽  
Upper Respiratory Tract ◽  
Test Results ◽  
Rt Pcr ◽  
Individual Participant

Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA), using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Findings Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 to 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Interpretation RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond ten days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias so the positivity rates are probably overestimated.

scholarly journals SARS-CoV-2 virus culture from the upper respiratory tract: Correlation with viral load, subgenomic viral RNA and duration of illness.

2020 ◽  
Author(s):  
Ranawaka APM Perera ◽  
Eugene Tso ◽  
Owen TY Tsang ◽  
Dominic NC Tsang ◽  
Kitty Fung ◽  
...  
Keyword(s):  
Viral Load ◽  
Upper Respiratory Tract ◽  
Genomic Rna ◽  
Rt Pcr ◽  
Mild Disease ◽  
Virus Rna ◽  
Duration Of Illness ◽  
Virus Culture ◽  
Upper Respiratory ◽  
Respiratory Specimens

In 68 respiratory specimens from a cohort of 35 COVID-19 patients, 32 of them with mild disease, we found SARS coronavirus-2 virus culture and sub-genomic RNA was rarely detectable beyond 8 days after onset of illness although virus RNA by RT-PCR remained detectable for many weeks.

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