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Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020

"retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20...

...The findings in this report are subject to at least three limitations. First, the data presented here are retrospective."

In this thread I will show that the lack of false positives makes these findings highly implausible, and I will show that other studies have had contradictory results.

Jorden MA, Rudman SL, et al. Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020. MMWR Morb Mortal Wkly Rep 2020;69:680–684. DOI: dx.doi.org/10.15585/mmwr.mm692

"The most widely utilized Nucleic Acid Amplification Test (NAAT) to detect SARS-CoV-2 RNA is the reverse transcriptase-polymerase chain reaction (RT-PCR) test, manufactured by many companies targeting one or more genomic regions of the virus...

...The FDA has published recommendations concerning the data and information that test manufacturers should supply in their application for Emergency Use Authorization (EUA)...

...Acceptable clinical performance is defined as a minimum 95% positive and negative percent agreement (PPA and NPA).

For a screening indication, the PPA recommendation remains at more than or equal to 95% and the NPA is raised to more than or equal to 98% to reduce false positive test results.

In actual use, the clinical sensitivity and specificity of many of these tests is lower in part because of issues surrounding sample collection, handling, and analysis."

Braunstein, Glenn D. MD; Schwartz, Lori MD, FACOEM; Hymel, Pamela MD, MPH, FACOEM; Fielding, Jonathan MD, MPH, MBA. False Positive Results With SARS-CoV-2 RT-PCR Tests and How to Evaluate a RT-PCR-Positive Test for the Possibility of a False Positive Result. Journal of Occupational and Environmental Medicine 63(3):p e159-e162, March 2021. | DOI: 10.1097/JOM.0000000000002138

journals.lww.com/joem/fulltext

TABLE 1 - Causes of False Positive SARS-CoV-2 RT-PCR Results

 Contamination during
  Sampling (eg, an infected worker or surfaces; aerosolization of virus during collection)
  Extraction (eg, aerosolization in containment hood)
  PCR amplification
  Production of Lab Reagents (eg, manufacturers of the positive control may have contaminated other reagents produced in the same facility; contamination of other consumables)
 Contamination of the equipment by high viral titer specimens (eg, sample carryover)
 Cross-reaction with other viruses (eg, other coronaviruses)
 Sample mix-ups
 Software problems
 Data entry or transmission errors
 Miscommunicating results
 Variations in parameters around the LOD and definition of an indeterminate result
 Assuming that an indeterminate result is a positive
 Non-specific reactions

Braunstein, Glenn D. MD; Schwartz, Lori MD, FACOEM; Hymel, Pamela MD, MPH, FACOEM; Fielding, Jonathan MD, MPH, MBA. False Positive Results With SARS-CoV-2 RT-PCR Tests and How to Evaluate a RT-PCR-Positive Test for the Possibility of a False Positive Result. Journal of Occupational and Environmental Medicine 63(3):p e159-e162, March 2021. | DOI: 10.1097/JOM.0000000000002138

journals.lww.com/joem/fulltext

Waiting for the truth: is reluctance in accepting an early origin hypothesis for SARS-CoV-2 delaying our understanding of viral emergence?

"Although the current canonically accepted timeline hypothesises viral emergence in Wuhan, China, in November or December 2019, a growing body of diverse studies provides evidence that the virus may have been spreading worldwide weeks, or even months, prior to that time.

However, the hypothesis of earlier SARS-CoV-2 circulation is often dismissed with prejudicial scepticism and experimental studies pointing to early origins are frequently and speculatively attributed to false-positive tests...

...Several studies performed independently by different groups retrospectively demonstrated the presence of antibodies and viral RNA in clinical samples and showed SARS-CoV-2 community circulation by detecting viral RNA in wastewater at times inconsistent with November 2019 emergence...

...Each study providing evidence for early circulation of SARS-CoV 2 might look inconclusive, but combining all data together reveals an emerging pattern...

...Despite the technical limitations of available early origin studies, even a remote possibility that positive tests indicate an early SARS-CoV-2 circulation should be considered sufficient to warrant the scaling up of research to more samples from more regions and through a wider timespan.

Time is running out: valuable samples that may contain the key to the understanding of SARS CoV-2 origin might already have been destroyed as their regulatory storage time requirements lapse."

Canuti M, Bianchi S, Kolbl O, et alWaiting for the truth: is reluctance in accepting an early origin hypothesis for SARS-CoV-2 delaying our understanding of viral emergence?BMJ Global Health 2022;7:e008386.

gh.bmj.com/content/7/3/e008386

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