Uncontrolled spread, p.47
Uncontrolled Spread, page 47
48.“Coronavirus (COVID-19) Update: FDA Provides More Regulatory Relief During Outbreak, Continues to Help Expedite Availability of Diagnostics,” US Food and Drug Administration press release, March 16, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-more-regulatory-relief-during-outbreak-continues-help.
49.Caroline Chen, Marshall Allen, and Lexi Churchill, “Internal Emails Show How Chaos at the CDC Slowed the Early Response to Coronavirus,” ProPublica, March 26, 2020.
50.Ibid.
51.Gerry Shih et al., “As Deadly Coronavirus Spreads, U.S. to Expand Screening of Passengers from China at 20 Airports,” Washington Post, January 27, 2020.
52.Meyer and Madrigal, “The Dangerous Delays in U.S. Coronavirus Testing Haven’t Stopped.”
53.Brett Murphy and Letitia Stein, “Coronavirus Response Delayed Despite Health Officials’ Private Alarm,” USA Today, January 26, 2021.
54.Tim Dickinson, “The Four Men Responsible for America’s COVID-19 Test Disaster,” Rolling Stone, June 2020.
55.Murphy and Stein, “Coronavirus Response Delayed Despite Health Officials’ Private Alarm.”
56.This policy would be changed in a footnote included in the CDC’s policy statement on March 8, 2020: “For healthcare personnel, testing may be considered if there has been exposure to a person with suspected COVID-19 without laboratory confirmation. Because of their often extensive and close contact with vulnerable patients in healthcare settings, even mild signs and symptoms (e.g., sore throat) of COVID-19 should be evaluated among potentially exposed healthcare personnel.” See US Centers for Disease Control and Prevention, “Updated Guidance on Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19),” March 8, 2020.
57.The CDC ultimately made the virus available to test manufacturers through BEI Resources.
The University of Texas said they could have a limited supply of extracted RNA available by February 14.
58.US Government Accountability Office, “Zika Supplemental Funding: Status of HHS Agencies’ Obligations, Disbursements, and the Activities Funded,” May 2018, https://www.gao.gov/assets/gao-18-389.pdf.
59.Stephen Hahn, “Remarks by FDA Commissioner Stephen Hahn to the American Clinical Laboratory Association,” March 4, 2020, https://www.fda.gov/news-events/speeches-fda-officials/remarks-fda-commissioner-stephen-hahn-american-clinical-laboratory-association-03042020.
60.Jayne Byakika-Tusiime et al., “Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults,” PLOS One 3, no. 12 (2008); World Health Organization, “WHO Statement on Removal of Two AIDS Medicines from List of Prequalified Products,” June 17, 2004, https://www.who.int/mediacentre/news/statements/2004/statement_aidsprequal/en/; and Lancet Editorial Board, “The Important World of Drug Prequalification,” Lancet 364, no. 9448 (2004).
61.C-SPAN, “Vice President Pence Meets with Diagnostic Lab CEOs,” March 4, 2020, https://www.c-span.org/video/?470004-1/vice-president-pence-meets-diagnostic-lab-ceos.
62.Scott Gottlieb (@ScottGottliebMD), “1/n On #coronavirus testing: The nations big clinical labs meet in Washington today for a convention and their CEOs are in town meeting with federal elected leaders. This is their moment. They ought to step up. They may be judged by what they now do.,” Twitter, March 4, 2020, 6:31 a.m.
Chapter 8: Not Enough Tests and Not Enough Labs
1.Recent publications have suggested there may still be viral replication, just at a very low level. RNA is labile, making low level replication one explanation for the continued presence of low levels of detectable viral RNA.
2.Apoorva Mandavilli, “Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.,” New York Times, January 19, 2021.
The science around using the quantity of RNA found in a sample as a way to determine continued infectivity is inexact. The same cycle threshold between two tests can reflect different amounts of RNA and even the same cycle threshold for the same test performed in two different labs can reflect different amounts of RNA. Also, there’s some data showing that even at high cycle thresholds, some individuals are still likely infectious.
3.“Coronavirus (COVID-19) Update: FDA Authorizes First Antigen Test to Help in the Rapid Detection of the Virus that Causes COVID-19 in Patients,” US Food and Drug Administration press release, May 9, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-antigen-test-help-rapid-detection-virus-causes.
4.In the case of the Abbott test, the antibodies on the paper surface were designed to bind to the coronavirus’s nucleocapsid, which is the protein shell of a virus, enclosing its genetic material. The protein is typically highly unique to each particular strain of a virus.
See US Food and Drug Administration, “EUA Authorized Serology Test Performance,” accessed February 26, 2021, https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance.
5.“Abbott’s Fast, $5, 15-Minute, Easy-to-Use COVID-19 Antigen Test Receives FDA Emergency Use Authorization; Mobile App Displays Test Results to Help Our Return to Daily Life; Ramping Production to 50 Million Tests a Month,” Abbott press release, August 26, 2020.
6.Initially, Abbott was able to manufacture 50 million tests a week from production sites it built in advance of its FDA approval; but the federal government cornered almost the entire initial supply, purchasing 150 million of the tests to direct them to nursing homes. See Michelle Fay Cortez, Cristin Flanagan, and Jordan Fabian, “U.S. Buys Almost All Abbott’s $5 Rapid Tests Made This Year,” Bloomberg, August 26, 2020.
7.“Abbott Begins Shipping BinaxNOW COVID-19 AG Self Test to Retailers Today,” Abbott press release, April 19, 2021.
8.As the Washington Post reported, “Health officials in several states say they have been allowed no say in where the new tests are being sent and sometimes don’t know which nursing homes will receive them until the night before a shipment arrives. That has left some facilities ill-trained in how to use the tests and what to do with results. And it may be contributing to false-positive test results—when people are identified as being infected but aren’t.” See William Wan and Lena H. Sun, “Trump Administration’s New Rapid Coronavirus Tests Plagued by Confusion and a Lack of Planning,” Washington Post, September 29, 2020.
9.Christopher Weaver, Anna Wilde Mathews, and Tom McGinty, “Many Nursing Homes Shun Free Covid-19 Testing Equipment,” Wall Street Journal, November 7, 2020.
10.US Centers for Disease Control and Prevention, “Interim Guidance for Antigen Testing for SARS-CoV-2,” December 16, 2020, https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html.
11.FDA did make clear through a variety of means, including an FAQ, that the test can be ordered by a provider off-label for screening but given the lower sensitivity, negative results should be considered presumptive.
12.Daniel Larremore et al., “Test Sensitivity Is Secondary to Frequency and Turnaround Time for COVID-19 Surveillance,” medRxiv, September 8, 2020, https://www.medrxiv.org/content/10.1101/2020.06.22.20136309v3; and Michelle Fay Cortez and Emma Court, “Abbott Test May Curb Virus Even Missing Some Cases, CDC Says,” Bloomberg, January 19, 2021.
13.Lisa Song, “Rapid Testing Is Less Accurate Than the Government Wants to Admit,” ProPublica, November 16, 2020.
14.Wan and Sun, “Trump Administration’s New Rapid Coronavirus Tests Plagued by Confusion and a Lack of Planning.”
15.“Of 3,725 antigen tests performed at 12 facilities, 60 came back positive, and on follow up testing with PCT, they identified 39 as false positives, or 60%.” See Ken Ritter and Sam Metz, “Nevada Reverses Ban on Rapid Tests After Federal Pushback,” Associated Press, October 9, 2020.
16.Nevada Department of Health and Human Services, “Discontinue the Use of Antigen Testing in Skilled Nursing Facilities Until Further Notice,” Technical Bulletin, October 2, 2020, http://dpbh.nv.govAiploadedFilesAdpbhnvgov/content/Resources/Directive%20to%20Discontinue%20Use%20of%20Antigen%20POC_10.02.2020_ADA_Compliant.pdf.
17.Alexis Madrigal and Robinson Meyer, “Why Trump’s Rapid-Testing Plan Worries Scientists,” Atlantic, October 9, 2020.
18.Alex Spanko, “As Federal Government Rolls Out Point-of-Care Units, Not All States Allow Nursing Homes to Use Them,” Skilled Nursing News, July 31, 2020.
19.Ritter and Metz, “Nevada Reverses Ban on Rapid Tests after Federal Pushback.”
20.US Food and Drug Administration, “Coronavirus (COVID-19) Update: FDA Takes Steps to Streamline Path for COVID-19 Screening Tools, Provides Information to Help Groups Establishing Testing Programs,” March 16, 2021, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-steps-streamline-path-covid-19-screening-tools-provides.
21.“Trump Interrupts Health Officials: ‘Anybody That Wants a Test Can Get a Test,’” Washington Post, March 7, 2020.
22.Matthew Perrone and Mike Stobbe, “US Labs Await Virus-Testing Kits Promised by Administration,” Associated Press, March 5, 2020.
23.“With current estimates (and this could change), 2.1 million tests would roughly translate to 850,000 Americans being able to undergo testing. “IDT and other manufacturers believe they can scale up production so that by the end of next week an additional 4 million tests could be shipped. This does not include the ramp up expected by large commercial or academic labs.” See US Food and Drug Administration, “Coronavirus (COVID-19) Update: White House Press Briefing by FDA Commissioner Stephen M. Hahn, M.D.,” March 7, 2020, https://www.fda.gov/news-events/speeches-fda-officials/coronavirus-covid-19-update-white-house-press-briefing-fda-commissioner-stephen-m-hahn-md-03072020.
24.COVID-19 Test Capacity (@COVID2019tests), Twitter, https://twitter.com/COVID2019tests; and Scott Gottlieb (@ScottGottliebMD), “Our last update on U.S. #COVID19 testing capacity. As high throughput systems come online this week, testing capacity will substantially increase nationwide. Any limitations will be the testing supply chain (reagents, swabs, sites, etc)—not platforms for conducting testing,” Twitter, March 16, 2020, 1:51 p.m.
25.Robinson Meyer and Alexis C. Madrigal, “The Dangerous Delays in U.S. Coronavirus Testing Haven’t Stopped,” Atlantic, March 9, 2020; and Chandelis Duster and Jacqueline Howard, “Health and Human Services Chief Says ‘We Don’t Know’ How Many Americans Have Been Tested for Coronavirus,” CNN, March 10, 2020.
26.Stephen Hahn, “Food and Drug Administration Budget Request for FY2021,” testimony before the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies, Committee on Appropriations, US House of Representatives, March 11, 2020.
27.Sanjay Gupta and Brett Giroir, “CNN Special Report, COVID WAR: The Pandemic Doctors Speak Out,” CNN, March 28, 2021.
28.“Roche’s Cobas SARS-CoV-2 Test to Detect Novel Coronavirus Receives FDA Emergency Use Authorization and Is Available in Markets Accepting the CE Mark,” Roche press release, March 13, 2020.
29.Puneet Souda, Westley Dupray, and Scott Mafale, “Life Science Tools and Diagnostics: Update #3: The Current State of COVID-19 Testing in the U.S.,” SVB Leerink, March 30, 2020; and David Lim, “Latest Coronavirus Testing Glitch: Not Enough Cotton Swabs,” Politico, March 16, 2020.
30.“Inslee Statement on Statewide Shutdown of Restaurants, Bars and Limits on Size of Gatherings Expanded,” Washington Governor press release, March 15, 2020, https://www.governor.wa.gov/news-media/inslee-statement-statewide-shutdown-restaurants-bars-and-limits-size-gatherings-expanded.
31.Weizhen Tan and Riya Bhattacharjee, “California Governor Issues Statewide Order to ‘Stay at Home’ as Coronavirus Cases Soar,” CNBC, March 20, 2020.
Chapter 9: Shortage after Shortage
1.WECT Staff, “CDC Recommends Healthcare Providers Assume Those with Mild Symptoms to Be Positive with COVID-19,” WCET NBC News 6, March 23, 2020.
2.Emma Court, Kristen Brown, and Neil Weinberg, “U.S. Finally Ramps Up Virus Testing, but Demand Still Outpaces Supply,” Bloomberg, March 27, 2020.
3.Katherine Eban, “How Jared Kushner’s Secret Testing Plan ‘Went Poof into Thin Air,’” Vanity Fair, July 30, 2020.
4.Lauren Webber and Christina Jewett, “Testing Swabs Run In Short Supply as Makers Try to Speed Up Production,” National Public Radio, March 18, 2020.
5.Lim, “Latest Coronavirus Testing Glitch: Not Enough Cotton Swabs.”
6.Charles Eichacker, “With $75.5M from the Feds, this Guilford Swab Maker’s Expansion Came Together in Weeks,” Bangor Daily News, June 16, 2020; and Maureen Milliken, “Puritan, Hardwood Suit Is Tale of Family Business Going in Opposite Directions,” Mainebiz, Feburary 25, 2020.
7.Olivia Carville, “America’s Covid Swab Supply Depends on Two Cousins Who Hate Each Other,” Bloomberg, March 18, 2021.
8.Charles Eichacker, “How a Family-Owned Company in Guilford Came to Host a Visit from the President,” Bangor Daily News, June 16, 2020.
9.Company documents.
10.Lewis Kamb, “Fed Shipment of Q-Tip-Style Coronavirus Swabs Puzzles Washington State Officials, Latest Wrinkle in Supply Woes,” Seattle Times, May 16, 2020.
11.The preferred materials for nasopharyngeal swabs are flock-tipped with nylon or spun with polyester. The preferred material for nasal swabs is spun with a foam tip. The polyurethane material in the foam-tipped swab is best for absorption in the nose and transferring to nitrocellulose test paper of lateral flow tests. But special—and in each case, different—machinery is required to manufacture the two kinds of swabs.
12.Carville, “America’s Covid Swab Supply Depends on Two Cousins Who Hate Each Other.”
13.“DOD Details $75 Million Defense Production Act Title 3 Puritan Contract,” US Department of Defense press release, April 29, 2020, https://www.defense.gov/Newsroom/Releases/Release/Article/2170355/dod-details-75-million-defense-production-act-title-3-puritan-contract/.
14.Scott Gottlieb, “Are We Prepared? Protecting the US from Global Pandemics,” statement before the Committee on Homeland Security and Governmental Affairs, US Senate, February 12, 2020.
15.Katherine J. Wu, “‘It’s Like Groundhog Day’: Coronavirus Testing Labs Again Lack Key Supplies,” New York Times, August 15, 2020.
16.US Food and Drug Administration, “Coronavirus (COVID-19) Update: December 28, 2020,” December 28, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-december-28-2020.
17.Staff Reporter, “COVID-19 Testing Scales Up with Automation but Supply Chain Disruptions Persist,” Modern Healthcare, July 7, 2020.
One company, Hamilton, made many of the pipettes and also manufactured the tips. They maintained the intellectual property over the devices, and the service agreements that they had in place often required that the Hamilton pipettes be used with Hamilton tips. This was done to maintain oversight of the quality of the testing systems. Hamilton worked hard to stand up a new manufacturing line and started to allow labs to use other vendors for the pipette tips without violating their service agreements. But when Hamilton allowed other tips to be used, they needed to be validated to work with the systems. Most alternate vendor tips didn’t meet the established criteria and could not be used as substitutions for Hamilton tips. It proved once again how hard it is to improvise in a crisis. These supply issues needed to be worked out in advance. We hadn’t prepared for what would be needed in a crisis.
18.Caroline Chen (@CarolineYLChen), “You know what’s infuriating? That Utah’s public health lab could do more genomic sequencing to look out for variants . . . if only it had more pipette tips.,” Twitter, February 7, 2021, 9:43 a.m.
19.Kate Sheridan, “How Blackouts, Fires, and a Pandemic are Driving Shortages of Pipette Tips—and Hobbling Science,” STAT, April 28, 2021.
20.US Food and Drug Administration, “Medical Device Shortages During the COVID-19 Public Health Emergency,” accessed February 26, 2021, https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/medical-device-shortages-during-covid-19-public-health-emergency.
21.Farhad Manjoo, “How the World’s Richest Country Ran Out of a 75-Cent Face Mask,” New York Times, March 25, 2020.
22.Amanda Watts and Alison Main, “The US Has a Stockpile of Masks, Health Secretary Says,” CNN, February 26, 2020.
23.Lawrence Wright, “The Plague Year,” New Yorker, December 28, 2020.
24.David Sanger, Zolan Kanno-Youngs, and Nicholas Kulish, “A Ventilator Stockpile, with One Hitch: Thousands Do Not Work,” New York Times, April 20, 2020; and Rick Sobey, “Donald Trump: U.S. Has 9,000 Ventilators in Federal Stockpile,” Boston Herald, April 6, 2020.
25.Sanger, Kanno-Youngs, and Kulish, “A Ventilator Stockpile, with One Hitch: Thousands Do Not Work.”
26.Kim Chandler, “Some States Receive Masks with Dry Rot, Broken Ventilators,” Associated Press, April 4, 2020.
27.Lena H. Sun, “Inside the Secret U.S. Stockpile Meant to Save Us All in a Bioterror Attack,” Washington Post, April 24, 2018.
28.Jon Swaine, Robert O’Harrow Jr., and Aaron C. Davis, “Before Pandemic, Trump’s Stockpile Chief Put Focus on Biodefense. An Old Client Benefited,” Washington Post, May 4, 2020.
29.Scott Gottlieb, “Beat Tomorrow’s Pandemic Today,” Wall Street Journal, May 23, 2021.
30.Interagency Task Force in Fulfillment of Executive Order 13806, “Assessing and Strengthening the Manufacturing and Defense Industrial Base and Supply Chain Resiliency of the United States,” US Department of Defense, September 2018, https://media.defense.gov/2018/Oct/05/2002048904/-1/-1/1/ASSESSING-AND-STRENGTHENING-THE-MANUFACTURING-AND%20DEFENSE-INDUSTRIAL-BASE-AND-SUPPLY-CHAIN-RESILIENCY.PDF.
