Research on COVID-19 Testing

Diagnosing SARS-CoV-2 Infection: The Danger of Over-reliance on Positive Test Results
Andrew N. Cohen, Bruce Kessel and Michael G. Milgroom
medRxiv 28 Sept 2020 (Version 1 posted 1 May 2020)
Summary: Contrary to the practice in previous epidemics, in addressing COVID-19 health authorities have treated a single positive result from a PCR-based test as confirmation of infection, irrespective of signs, symptoms and exposure. This is based on a widespread belief that positive results in these tests are highly reliable. However, evidence from external quality assessments and real-world data indicate enough a high enough false positive rate to make positive results highly unreliable over a broad range of scenarios. This has clinical and case management implications, and affects an array of epidemiological statistics, including the asymptomatic ratio, prevalence, and hospitalization and death rates, as well as epidemiologic models. Steps should be taken to raise awareness of false positives and reduce their frequency. The most important immediate action is to check positive results with additional tests, at least when prevalence is low.
Preprint and Supplemental Material

SARS CoV 2 Mass Testing Endangers Residents of Long-Term Care Facilities
Andrew N. Cohen and Bruce Kessel
SSRN 21 July 2020
Summary: Mass-testing for SARS-CoV-2 with RT-PCR has been widely implemented at nursing homes and assisted-living facilities in the U.S. and Canada. If prevalence is low, as is often the case in mass testing, and if false positive rates are similar to rates in similar RT-PCR tests, a large proportion of the positive results will be false. We here report numerous records of false positives at such facilities. Residents that test positive are routinely sequestered with other residents that tested positive. This exposes uninfected, false-positive-tested individuals to infected individuals, thereby increasing the risk that they will become infected with COVID-19. Testing meant to protect the frail and elderly may instead be endangering them. Requiring confirmation of positive results with a second test would eliminate most false positives. A few authorities have begun to implement this measure; all should.

Analysis Should Address Test Specificity/Sensitivity, and Adequate Assessment of Asymptomatic Status (posted 7 June 2020)
Problems with Review: False Positives; Inadequate Longitudinal Study; Overly Narrow Symptom Definitions; Poor Evidence of Asymptomatic Transmission (posted 2 July 2020)
Andrew N. Cohen and Bruce Kessel
Annals of Internal Medicine
Summary: This review concluded that asymptomatic persons (meaning individuals that developed no symptoms over their entire infection period) account for 40-45% of SARS-CoV-2 infections, and that transmission by asymptomatic persons is a significant factor in the spread of COVID-19. However, the review failed to consider the potential for false positive test results, so that the asymptomatic carriers of SARS-CoV-2 counted in the cited studies may not have been carriers. It also failed to address the necessity of screening individuals for all significant COVID-19-like symptoms and to screen them over a long-enough period, so that the asymptomatic carriers counted in the studies may not have been asymptomatic. Finally, the evidence of asymptomatic transmission reported by the review is much too weak to support its conclusion. This is not to say that there are no asymptomatic carriers and no asymptomatic transmission, rather that the evidence reported here is insufficient to support the conclusions that a large proportion of infected individuals are asymptomatic and that asymptomatic transmission is a major factor in the spread of COVID-19.
Article, Comments, and Authors’ Response (posted 15 July 2020)

Why Don’t Seniors Get the Same COVID-19 Tests as Athletes?
Original title: We protect professional athletes from testing errors. Why not the elderly?
Bruce Kessel and Andrew N. Cohen
Orlando Sentinel July 31, 2020
Summary: We protect professional athletes against testing errors, by checking positive results with further tests. Why don’t we provide the same protection to the elderly and the frail, for whom a false positive result can be life-threatening?

Single Coronavirus Pretest will not Protect Tourism Workers
Bruce Kessel
Honolulu Star-Advertiser September 29, 2020
Summary: To protect Hawai’i against a problematic number of infected visitors, arriving travelers should be tested both before arrival and on arrival: pretest and retest.

Why is a marine biologist investigating false positives in COVID-19 testing?
It was natural after a decade of investigating false positives in similar tests used in environmental monitoring: see What Mussels Can Teach Us, reported by Richard Harris on NPR’s Weekend Edition for June 14, 2020.

Johann Holzmann asked about an inconsistency between the median false positive rate derived from our review of 43 external quality assessments of similar tests and the low positivity rate reported in certain countries.
Read his question and Andrew Cohen’s answer

In March, Dr. Guihua Zhuang and eight colleagues published a paper in the Chinese Journal of Epidemiology that attempted to raise awareness about the potential for a large portion of positive results to be false, even if the false positive rate is low, when prevalence is also low. The paper was retracted soon after it was published. It was subsequently cited, incorrectly, by U.S. health officials. Nothing in the paper appears to justify its retraction after it was published, and I am inclined to agree with speculation that it was retracted for political rather than scientific reasons.
Here is the paper (in Chinese), my translation (based on GoogleTranslate), and the English-language abstract as it appeared in PubMed in March.

Did retesting positive results, as we recommended, keep the Tour de France on course?
Forewarned by some apparent false positive results in earlier races, which under the Tour rules could easily have disqualified entire teams, the organizers decided on the day before the Tour that they would retest all positive results in order to reduce the incidence of false positives.
When is a Positive Not a Positive? COVID-19 and the Tour de France
Tour de France to Carry Out Secondary COVID-19 Testing to Avoid False Positives

False positives and Parliament
When results from our analysis of the potential range of false positive rates were summarized in a UK government report and then cited in Parliament, the Science Editor at The London Times asked for clarification.
Coronavirus Analysis