Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

Miller, Tyler E.; Beltran, Wilfredo F. Garcia; Bard, Adam Z.; Gogakos, Tasos; Anahtar, Melis N.; Astudillo, Michael; Yang, Diane; Thierauf, Julia; Fisch, Adam S.; Mahowald, Grace K.; Fitzpatrick, Megan J.; Nardi, Valentina; Feldman, Jared; Hauser, Blake M.; Caradonna, Timothy M.; Marble, Hetal D.; Ritterhouse, Lauren L.; Turbett, Sara E.; Batten, Julie M.; Georgantas, Nicholas Zeke; Alter, Galit; Schmidt, Aaron; Harris, Jason B.; Gelfand, Jeffrey A.; Poznansky, Mark C.; Bernstein, B; Louis, David N.; Dighe, Anand S.; Charles, Richelle C.; Ryan, Edward T.; Branda, John A.; Pierce, Virginia; Murali, Mandakolathur R.; Iafrate, A. John; Rosenberg, Eric S.; Lennerz, Jochen K.

doi:10.1096/fj.202001700rr

Cited by 122 publications

(100 citation statements)

References 33 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We derived an infectivity profile based on transmission pairs of COVID-19 infected individuals 17 , a basic reproduction number of R 0 = 2.5, and an incubation period of 8.29 days 18 , and estimated the temporal diagnostic sensitivity of RT-PCR tests 19 (Supplementary Table 1 ). Specifying 30.8% of infections as remaining asymptomatic across the disease course 20 , 21 , we estimated that perfect isolation of cases upon symptom onset would reduce the reproduction number to 1.6, with 1.2 secondary cases occurring during the incubation period (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As quarantined (asymptomatic) cases proceed through their quarantine, they simultaneously progress through their infectious course. Symptom onset will send a substantial fraction of infected individuals to isolation and diagnostic sensitivity decreases for the remainder 19 , leading to slightly diminishing benefits of “exit” tests performed later than day six.…”

Section: Resultsmentioning

confidence: 99%

“…We utilized the post-symptom onset temporal diagnostic sensitivity for RT-PCR tests of infected individuals 19 , fitting a logistic regression function to the diagnostic sensitivity data (obtained through digitization with WebPlotDigitizer 35 ) from zero to 25 days post-symptom onset through minimization of least squares. To infer the diagnostic sensitivity prior to symptom onset, we first used this function to perform a slight extrapolation of the diagnostic sensitivity back to the peak, which occurred slightly prior to symptom onset.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Optimal COVID-19 quarantine and testing strategies

et al. 2021

View full text Add to dashboard Cite

For COVID-19, it is vital to understand if quarantines shorter than 14 days can be equally effective with judiciously deployed testing. Here, we develop a mathematical model that quantifies the probability of post-quarantine transmission incorporating testing into travel quarantine, quarantine of traced contacts with an unknown time of infection, and quarantine of cases with a known time of exposure. We find that testing on exit (or entry and exit) can reduce the duration of a 14-day quarantine by 50%, while testing on entry shortens quarantine by at most one day. In a real-world test of our theory applied to offshore oil rig employees, 47 positives were obtained with testing on entry and exit to quarantine, of which 16 had tested negative at entry; preventing an expected nine offshore transmission events that each could have led to outbreaks. We show that appropriately timed testing can make shorter quarantines effective.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Optimal COVID-19 quarantine and testing strategies

et al. 2021

View full text Add to dashboard Cite

show abstract

“…3 These "false negatives" have been ascribed to imperfect sensitivity of polymerase chain reaction and antibody testing, particularly in patients presenting at different times during their disease course. 12,13…”

Section: Limitationsmentioning

confidence: 99%

Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic

et al. 2021

View full text Add to dashboard Cite

IMPORTANCETo date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. OBJECTIVE To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. DESIGN, SETTING, AND PARTICIPANTS A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. MAIN OUTCOMES AND MEASURES Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. RESULTS Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. CONCLUSIONS AND RELEVANCEIn this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.

show abstract

“…To prevent disease importation and transmission during the silent asymptomatic and pre-symptomatic stages of infection, we implemented routine nasopharyngeal (NP) and saliva PCR testing of staff with a frequency of 7 days (39). The probability of case detection at the time of testing post-infection was determined by the temporal diagnostic sensitivity (40) inferred from fitting a sensitivity function to the percent positivity data of NP testing (41). Both tests were assumed to have a specificity of 100%.…”

Section: Interventionsmentioning

confidence: 99%

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada

Vilches

Nourbakhsh

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundCOVID-19 has caused severe outbreaks in Canadian long-term care facilities (LTCFs).ObjectiveTo evaluate the effect of mitigation measures in LTCFs including routine testing of staff and vaccination of staff and residents.DesignAgent-based transmission model parameterized with disease-specific estimates, temporal sensitivity of nasopharyngeal (NP) and saliva testing, preliminary results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada.SettingCharacteristics of staff and residents were included in the model with age-dependent risk of hospitalization and deaths, calibrated to the cumulative incidence of COVID-19 reported in these settings.ParticipantsSynthetic staff and resident populations.InterventionsRoutine NP and saliva testing of staff; vaccination of residents and staff.MeasurementsDaily incidence and attack rates in the LTCF using large-scale model simulations; estimates of hospitalizations and deaths and their 95% credible intervals.ResultsWeekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 20.3% (95% CrI: 18.7-21.8%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 81.4% (95% CrI: 80.6-82.2%), and 82.1% (95% CrI: 81.5-82.7%), respectively.LimitationsTimelines of vaccine distribution and compliance rates with routine testing are key parameters affecting strategy outcomes.ConclusionRoutine testing of staff reduces silent transmission in LTCFs. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

show abstract

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

Cited by 122 publications

References 33 publications

Optimal COVID-19 quarantine and testing strategies

Optimal COVID-19 quarantine and testing strategies

Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada

Contact Info

Product

Resources

About