Monday, May 11, 2020

How long does a COVID-positive patient remain infectious?

I wanted to know how long a patient remains infective after testing  COVID positive, given that we are planning on waiting 2 weeks after a positive test before retesting, and given that the second test has a non-negligible false negative rate. Is two weeks long enough? It appears so, as much as we can tell from available data. These data are all right-skewed bell curves, so obviously one can't be precise in giving an exact number of days because of the long skinny "tail" of a bell curve. This was a quick Google search, not a careful review. My comments are in square brackets.

[It's important to distinguish between infectiveness vs. detection of virus. The duration of infectiveness with COVID seems to start 2 days before symptoms and declines rapidly 7 days after symptom onset, even though vital particles are detectable for 21 days after symptom onset: ]

Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature Apr 15, 2020

"We estimated that 44% (95% confidence interval, 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage..."

"serial interval (duration between symptom onsets of successive cases in a transmission chain)...based on 77 transmission pairs obtained from publicly available sources within and outside mainland China...the serial interval was estimated to have a mean of 5.8 days (95% confidence interval (CI), 4.8–6.8 days) and a median of 5.2 days (95% CI, 4.1–6.4 days)...we inferred that infectiousness started from 2.3 days (95% CI, 0.8–3.0 days) before symptom onset and peaked at 0.7 days (95% CI, −0.2–2.0 days) before symptom onset... Infectiousness was estimated to decline quickly within 7 days.

"We detected high viral loads soon after symptom onset, which then gradually decreased towards the detection limit at about day 21."
https://www.nature.com/articles/s41591-020-0869-5#Fig1

[The sensitivity and specificity of COVID PCR testing: In the lab, tests achieve "at least 96 percent specificity on negative samples"
https://spectrum.ieee.org/the-human-os/biomedical/diagnostics/testing-tests-which-covid19-tests-are-most-accurate ]

[But real-world clinical specificity has to do with multiple factors (reaching nasopharynx accurately with the swab, contamination of the specimen, storing and transporting the sample, delays etc.)
https://diagnostics.roche.com/us/en/roche-blog/COVID-19-testing-what-you-need-to-know-about-test-accuracy.html ]

False Negatives and Reinfections: the Challenges of SARS-CoV-2 RT-PCR Testing. Am So Microbiol Apr 27, 2020

"There currently is no gold-standard diagnostic test for SARS-CoV-2 since the virus is new to us."

"NP swabs have on the order of 100,000 (10E5) to 1,000,000 (10E6) cp/mL [viral copies per mL] of viral RNA. Even the less sensitive tests have LODs in the range of 1000s [10E3] of cp/mL, so the levels of RNA in clinical samples during acute infections should be easily detectable."

"...a test with good analytical sensitivity and specificity does not necessarily have good clinical sensitivity and specificity."

"We are learning something new every day about the best specimen types, collection methods and testing platforms for SARS2-CoV detection. These variables could help explain why some SARS-CoV-2 tests are negative when in fact, the patient has clinical disease...RNA is less stable than DNA, so if a specimen is not transported or stored appropriately, the risk of a false-negative RT-PCR result increases."

"peer-reviewed study...demonstrated that the virus was detectable by RT-PCR in patients who survived COVID-19 for up to 37 days, with a median time of 20 days...Lingering positive results are possibly explained if viral RNA remains in tissues for a considerable amount of time, even when the viral particles capable of causing infection have been cleared."

"As yet, there is no consensus on how accurate our testing is, and given the potential for asymptomatic carriage and prolonged viral shedding post-infection, we likely have a long road ahead and many lessons to learn."

https://asm.org/Articles/2020/April/False-Negatives-and-Reinfections-the-Challenges-of

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