The Editors in
Even with vaccines widely available and better data available about COVID-19, there are still some...
Still, much more COVID-19 testing cycle threshold (Ct) transparency is required in Rhode Island, and across the United States
BY ANDREW BOSTOM, M.D.
“We know that a strategic asymptomatic testing plan is one of our strongest lines of defense against the spread of COVID-19.”
Is this indeed a tenable, evidence-based strategy to “limit” COVID-19 spread? Simply put, no.
During a January 28, 2020 Health and Human Services presser, Dr. Anthony Fauci emphasized, “in all the history of respiratory-borne viruses of any type, asymptomatic transmission has never been the driver of outbreaks.” Here are his remarks in full:
“Historically people need to realize that even if there is some asymptomatic transmission [of covid-19], in all the history of respiratory-borne viruses of any type, asymptomatic transmission has never been the driver of outbreaks. The driver of outbreaks is always a symptomatic person. Even if there’s a rare asymptomatic person that might transmit, an epidemic is not driven by asymptomatic carriers”
Perhaps Dr. Fauci had in mind, “historically,” this 2009 review co-authored by Rhode Island Hospital’s own Head of Infection Control, Dr. Leonard Mermel, which concluded, regarding influenza transmission:
“Based on the available literature, we found that there is scant, if any, evidence that asymptomatic or presymptomatic individuals play an important role in influenza transmission”
A study of COVID-19 transmission in South Korea also supports Fauci’s generic view, based on previous respiratory virus outbreaks. Among 97 confirmed COVID-19 case-patients in this study (published by the Centers For Disease Control and Prevention [CDC] journal, MMWR), 4 (4.1%) remained asymptomatic during the 14-days of monitoring. None of the 4 household member contacts of these asymptomatic case-patients exhibited COVID-19 symptoms nor tested positive after 14 days of quarantine. In contrast, 34 of 210 household members who had contact with symptomatic case-patients contracted COVID-19, translating to a secondary attack rate of 16.2% (34/210).
Drs. Clare Craig and Jonathan Engler debunked the rather corrosive mythology of asymptomatic COVID-19 spread in a December 19, 2020 review:
“… after examination of the most frequently-cited papers in this area available to date, we are struck by the paucity of persuasive evidence of anything but the most minor of symptoms resulting from supposed asymptomatic spread, most or all of which (i.e., asymptomatic spread) could be misdiagnoses and in any event are at no more than anecdotal level”
Indeed Craig and Engler concluded there was “no evidence,” beyond China, “that anyone has developed even moderate COVID-19 based on true asymptomatic spread, as opposed to pre-symptomatic spread.” They further noted the veracity-compromising impact of a totalitarian Chinese Communist April, 2020 “mandate” that, “all academic papers on Covid-19 will be subject to extra vetting before being submitted for publication.” Lastly, as Craig and Engler observe, this edict might explain a bizarre “volte face” in the Chinese medical literature on asymptomatic COVID-19 transmission:
“The reader will no doubt readily understand the challenges of relying heavily on the output of a highly controlled regime with an active interest in destabilizing the economies and political systems of other countries. It is notable in fact, that in what would seem to represent an abrupt volte face by the CCP, a further (presumably Government-approved) study from China was recently published (11/20/20) which entirely contradicts the earlier conclusions (i.e., now claiming effectively zero asymptomatic COVID-19 transmission) regarding the phenomenon of asymptomatic transmission, which had been driven by Chinese data in particular, early in the pandemic.”
Rhode Island Governor Raimondo’s dubious strategy of focusing on “asymptomatic testing” is rendered even more questionable by the inherent limitations of the gold-standard method of determining COVID-19 “asymptomatic cases” by reverse transcriptase polymerase chain reaction (rtPCR) testing. The rtPCR test method amplifies genetic sequences (i.e., nucleic acids from the virus’ core RNA [ribonucleic acid]) obtained in samples, typically, from nasopharyngeal swabs or saliva. This amplification of viral nucleic acid sequences is measured in the number of cycles before detection (Cts), a proxy for the total amount of live virus present, or “viral load.” An rtPCR COVID-19 assay system developed at the Harvard University/ Massachusetts Institute of Technology Broad Institute, currently determining COVID-19 “positivity” at 108 northeastern universities—including R.I.’s major colleges—described this exponential relationship:
“…the Ct values correlated strongly with the logarithm of (COVID-19) RNA concentration (R-squared > 0.99; indicating a very strong correlation), with the observed range from Ct =12 cycles to Ct = 38 cycles corresponding to viral loads ranging from ~1.9 billion copies/mL to (a mere!) 8 copies/mL, respectively (i.e., an ~250 million-fold difference!).”
Ct values from upper respiratory samples (nasopharyngeal and saliva specimens), symptom onset in relation to test date (STT), and the ability to culture live virus are strongly correlated. Lower Cts, meaning less amplification is required, and shorter STTs indicate a patient’s infectious potential is greater. Additional validating clinical data suggest lower Cts—and hence larger viral loads—are associated with higher COVID-19 mortality when patients are hospitalized for symptomatic COVID-19 pneumonia and/or other manifestations of being heavily infected by the virus. Conversely, a study that recorded Cts of patients, serially, during their hospitalization for diagnosed COVID-19 pneumonia, reported that increasing Cts were accompanied by decreasing disease severity (Sequential Organ Failure Assessment; SOFA) scores.
“If you get a Ct of ≥35, the chances of it being replication competent (i.e., infectious) are miniscule… you almost never can culture virus from a 37 threshold cycle. If somebody does come in with 37, 38, even 36, you gotta say it’s just dead nucleotides. Period.”
Moreover, there is no tenable evidence asymptomatic persons with “positive” COVID-19 rtPCR tests at Cts >30—particularly, K-12, or college age students—are at risk for severe COVID-19 infections themselves, nor that they pose a serious risk of infectious spread to others. For example, an analysis evaluating the infectiousness of patients hospitalized with COVID-19 reported that only viral loads > 10 million copies/mL, equivalent to Cts ≤ 25, were associated with isolation of infectious virus from the respiratory tract. A complementary systematic review published December 3, 2020, by the Oxford University Center for Evidence-Based Medicine confirmed that COVID-19 rtPCR testing patient sample Cts >30 (mean from 6 studies) are associated with an inability to culture live virus, i.e., are non-infectious.
Lastly, Rhode Island Hospital’s infectious diseases specialist Dr. Leonard Mermel published an online clinical review, June 10, 2020, with the straightforward title, “Disposition of patients with coronavirus disease 2019 (COVID-19) whose respiratory specimens remain positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) by polymerase chain reaction assay (PCR).” Dr. Mermel concluded:
“Patients with high SARS-Cov-2 cycle threshold (he references ≥ 34, or even ≥24) have not been found to have live virus in their respiratory secretions”
At minimum, the misguided policy of mass screening of asymptomatic R.I. residents demands transparent sharing of the “positive” Ct data recorded for all rtPCR tests conducted in the state and compiled by the Department of Health (DOH). Initially, my colleagues and I received an uncooperative response to a straightforward public information request for Ct data in the state’s possession. The RIDOH instead levied some $3000.00 in upfront fees to gather this public information already paid for by taxpayer dollars—indicating it had chosen to be opaque about these potentially clarifying and reassuring data (see pdf of correspondence: RI reply to FOIA 10.28.20_redacted SD).
As described by the Rhode Island Center For Freedom and Prosperity, ultimately the RIDOH relented (in part) within 24 hours of a petition campaign launched by the Center:
Despite months of stonewalling of prior APRA (access to public records act) requests—and just one day after a petition campaign by the RI Center for Freedom & Prosperity sent over 1,000 emails to various state-government officials, including the DOH and the governor—the Center has obtained information released to a persistent citizen (independent of, but in parallel to our own request) by the state Executive Office of Health and Human Services; partial data covering a limited number of positive Covid-19 tests performed before July 2020.
The RI Center for Freedom & Prosperity press release included my own summary observations about the rtPCR Ct data from some ~5000 tests RIDOH provided (Note: we received our own RIDOH copy several days later; see Excel file link below):
“This first public revelation of cycle threshold (Ct) data, from ~ 5,000 RIDOH COVID-19 rtPCR positive tests from late February through the end of June, reveals that a considerable number (36.2%) of these positive tests occurred at a Ct > 33, a level generally considered by the medical community to be associated with extremely low COVID-19 infectiousness. Initial analysis of this data also confirms the need for all future RIDOH reports of daily positive test results to include breakdowns of the Ct data. Deeper analysis of even more data can be immensely important in determining more data-driven, targeted, and effective public policies. I join with the Center in petitioning the state of Rhode Island to follow Florida’s lead and to immediately begin collecting and [ultimately] reporting Ct data for all COVID-19 PCR tests.”
Bearing in mind the recent Oxford University Center for Evidence-Based Medicine review that found mean COVID-19 rtPCR test Cts> 30 were associated with non-infectiousness, 51% of the RIDOH sample had Cts above 30. Even lower Cts may merit re-consideration. A 9/6/20 Times of India report with the headline “COVID-19 test reports must also state cycle threshold value: Doctors” described the efforts of Indian pulmonary and pathology laboratory medicine MDs to promote the use of Ct data for patient clinical management:
“If the value is between 20 and 25, home isolation can be advised, but the patient must be monitored through online consultations. Hospital admission is a must in cases where the value is less than 20. This is particularly necessary for patients aged 50 or more who have comorbidity”
No clinical guidelines were provided for Cts >25, which clearly suggested Cts in this range indicated less acuity—consistent with the clinical laboratory correlation study of COVID-19 patients by Bullard and colleagues, who reported: “Infectivity of patients with Ct >24 and duration of symptoms >8 days may be low.” Fully 66%–two-thirds—of the RIDOH sample had Cts above 25.
In the absence of any direct clinical linkage data, my colleague, Dr. Todd Kenyon, conducted two further elegant “ecologic” analyses merging the ~5000 RIDOH Ct dataset to public domain RIDOH findings on rtPCR test “positivity” and COVID-19 mortality trends. Dr. Kenyon chose Ct > 32 (figure just below), consistent with the findings from this 10/24/20 report, as his cutpoint for COVID-19 “non-infectiousness”:
The two figures that follow summarize Dr. Kenyon’s analyses of the RIDOH Ct dataset. They demonstrate that, as the COVID-19 pandemic ebbed in severity by mid-to-late May through early June, Cts drifted upwards into the >32, or non-infectious, range. This upward drift, furthermore, was accompanied by a readily discernible decline in COVID-19 mortality in the state.
Rhode Islanders are entitled to know the Ct values for any of their individual “positive tests” and to have the statewide trends for these “positive test” data, i.e., weekly, if not daily, updates at the R.I. DOH website (“Rhode Island Covid-19 Response Data”) made public, in a bar graph display: percentage of Cts ≤ 20; 21-25; 26-30; 31-35; and >35.
As of Dec. 18, 2020, 69.3% of the state’s COVID-19 deaths (1133/1644) had accumulated from nursing homes and elder assisted living facilities, with 60% of the state’s total occurring in those ≥ 80 years old, including 27% among those 90+ years old. In stark contrast, only 18% of these deaths are among all Rhode Islanders < 70 years old. Expressed as crude mortality per 100,000, the COVID-19 death rate is 34/100,000 for those < 70 years old, while it is 56-fold higher in those ≥ 80 years old, i.e., 1891/100,000.
“Positive test” hysteria, absent transparent release of the accompanying Ct data, and simultaneous acknowledgment of the unchanging COVID-19 mortality demography, i.e., heavily skewed toward those at or above life expectancy in the state (=79.9 years), is ghoulishly dishonest.
Hope springs eternal that Rhode Islanders will unyieldingly demand such transparency of their governmental and bureaucratic overlords.