COVID-19 PCR tests are highly sensitive and specific for the virus SARS-CoV-2; the majority of positive results are true positives; there is no evidence that budesonide or HCQ are useful as COVID-19 treatments

On 16 and 17 April 2021, the Health and Freedom Conference was held in Tulsa, Oklahoma, an event organized by entrepreneur Clay Clark that was attended by over 4,000 people. The aim of the conference was to criticize the measures taken in response to the COVID-19 pandemic in the U.S., in relation to what some perceive as a loss of individual freedoms.

The event featured a number of speakers, including Mike Adams, Simone Gold, and several physicians and religious pastors. A video clip of the event was posted on Facebook by American Media Periscope on 21 May 2021 and went viral, receiving 45,000 interactions in five days.

The video showed several individuals making claims about the COVID-19 pandemic. For example, Clark and other speakers claimed that COVID-19 models were intentionally false and that COVID-19 PCR tests are producing largely false results.

Other speakers at the conference also claimed that “100% effective” COVID-19 remedies, specifically budesonide and hydroxychloroquine, are being withheld from the public. This review explains why these claims are misleading and unsupported.

Claim 1 (Inaccurate): The PCR tests are “falsely calibrated”

Apart from COVID-19 models, the conference also discussed PCR tests. Clark claimed that the tests are “falsely calibrated”, saying “PCR tests are supposed to be set at 17 cycles, those are set at 40 cycles, and so their results are false”. Another speaker at the conference, orthopedic surgeon Rob Marsh, claimed that “[the virus] is magnified so much that the World Health Organization came out in January and said that at 40 cycles it’s a 100% false”. 

These allegations imply that many positive COVID-19 PCR test results are false positives, another inaccurate claim that has been repeated throughout the pandemic, as documented by Health Feedback here and here.

As Health Feedback explained in this review, the COVID-19 PCR test detects the presence of the virus’ genetic material in samples such as nasopharyngeal swabs. This is achieved by “amplifying” (making new copies) of a particular segment of the virus’ genetic code. The number of cycles that are run during a PCR test determines how much the genetic material is amplified, and the number of cycles required to yield a positive test result depends on the amount of virus present in a sample. 

The higher the amount of genetic material present in the sample, the fewer cycles needed to reach the threshold considered as “positive”.The threshold considered as positive is also known as the cycle threshold (Ct) value. A positive PCR test with a low Ct indicates that the sample has a large amount of viral genetic material, while a PCR with a high Ct will detect the virus in samples with a low viral load.

A false-positive result occurs when the test is positive but the person isn’t infected^[1]. The WHO published an information notice in January 2021 to remind users to adhere to manufacturers’ instruction for using PCR tests and to be careful when interpreting test results

At no point did the WHO information notice state that results above a certain Ct were “100% false”, as claimed. There also isn’t evidence for Clark’s claim that PCR tests must have a Ct of 17 to be considered positive, nor did he present any. PCR testing is a tool for diagnosing SARS-CoV-2 with high specificity and sensitivity, and is able to accurately detect the virus, even in low amounts.

Claim 2 (Misleading): Models that predicted 2.2 million people will die are intentionally false

At the beginning of his speech in the video, Clark claimed “models that say that 2.2 million people will die are false, intentionally false”. While a model predicted this number of deaths in the U.S., this does not mean that the model was intentionally false, as Clark alleged.

On 16 March 2020, when COVID-19 had already caused deaths in several countries and measures were being implemented to prevent the uncontrolled spread of the disease, researchers from Imperial College London published a study modelling the expected effects of different measures to curb contagion^[2].  

The aim of this study, led by epidemiologist Neil Ferguson, was to seek the best possible measures to reduce infections and avoid a healthcare system collapse, thus reducing COVID-19 deaths. The measures studied included home isolation of symptomatic patients, voluntary home quarantine, physical distancing, and closure of schools and universities.

The study projected 510,000 deaths in Great Britain and 2.2 million deaths in the U.S. between April and August 2020 due to COVID-19, if none of the aforementioned measures were taken. Subsequent analyses by other researchers corroborated the reproducibility and predictive capability of the study^[3].

According to the statistics website Our World in Data, which collects health data from official sources, the death toll from COVID-19 in the U.S. at the end of August 2020 was 184,000. This number is well below the 2.2 million projected deaths. However, that forecast was conditional on not taking measures to mitigate COVID-19 transmission.

Between March and April 2020, numerous U.S. states implemented stay-at-home policies. Restrictions on international travel were also implemented in March 2020. The effectiveness of such measures in reducing the transmission of COVID-19 was corroborated in other studies^[4,5].

The discrepancy between the number of deaths projected in the model from March 2020 and the actual death toll is because in the real world, measures were implemented to reduce the transmission of COVID-19, whereas the projection was based on the assumption that no actions would be taken against the spread of the disease.

Therefore, the fact that the actual death toll from COVID-19 in the U.S. is lower than the number of deaths projected in the study doesn’t mean that the latter was intentionally false, as claimed. Rather, the reduced death toll in real life illustrated the effectiveness of public health measures, such as physical distancing and quarantine, at mitigating the impact of the pandemic.

Claim 3 (Unsupported): Budesonide can be used as a treatment for COVID-19

In the video, Clark claimed that “the treatments that are 100% effective are being banned for false reasons”. Another conference speaker, physician Richard Bartlett, claimed that the drug budesonide could be used in the treatment of COVID-19, and that the director of the U.S. National Institute of Allergy and Infectious Diseases “Anthony Fauci personally targeted budesonide because it was a threat”. His claims regarding the use of budesonide for the treatment of COVID-19 were previously debunked (here and here).

Budesonide is a corticosteroid medication used to prevent shortness of breath, chest tightness, wheezing, and coughing caused by asthma. It is an oral inhalation medication that works by decreasing inflammation and irritation in the airways to make breathing easier.

At the conference, Bartlett referred to an interview between Fauci and actor Matthew McConaughey, in which the use of budesonide was mentioned. The relevant transcript of the video (at the 7:19 mark in the video) is provided below. In this part of the interview, Fauci addressed common claims, one of which was about the use of budesonide in the treatment of COVID-19:

McConaughey: “Inhaled generic budesonide protects from secondary bacterial infection and the use of zinc does interfere with the virus replication of code.”

Fauci: “All of that in vitro can work, but there is no evidence now that what you mentioned has any clinical effect. The thing that happens a lot which confuses people, you get viruses, you put them in a plate or in a culture and you throw all kinds of things in there. And many compounds suppress the replication. But when you get to a clinical trial and you give it to people with the disease, more often than not, those things don’t have any beneficial effect. Some do, because if something is going to work in vivo, it likely will work in a test tube. But there are many more things that work in the test tube that don’t work in the body.”

McConaughey: “Okay. Is there any downside to…? There are people that believe that budesonide and taking zinc is working, is there any downside to doing it?”

Fauci: “You know, there’s a placebo effect to make you feel better and less anxious, but in reality, Matthew, it doesn’t have any effect.”

A study published in April 2021 found that treating COVID-19 patients with budesonide at the onset of the disease reduced the likelihood of needing urgent medical care and also reduced time to recovery^[6]. However, the study had some statistical limitations, due to the low number of patients in the randomized trial included. This means that it is difficult to make reliable conclusions based on the results and further research is needed^[7].

In October 2020, the U.S. Food and Drug Administration (FDA) issued a warning letter to a pharmaceutical company concerning budesonide, due to lack of any risk information regarding the use of this drug in the treatment of symptoms associated with COVID-19. Overall, there isn’t sufficient evidence supporting the use of treating COVID-19 Therefore, it has not been approved for this purpose, as possible side effects in COVID-19 patients are unknown.

Claim 4 (Unsupported): Hydroxychloroquine can be used to treat COVID-19

Another conference speaker, cosmetic surgeon Keith Rose, claimed that hydroxychloroquine is an effective COVID-19 treatment, citing the drug’s allegedly successful use against the disease in India. Rose also claimed that its use had been recommended against SARS-CoV-1 in a report in 2003. Clark alleged that hydroxychloroquine is one of the “100% effective” treatments for COVID-19.

Hydroxychloroquine is a drug used as an antimalarial, as well as a treatment for the autoimmune diseases lupus and rheumatoid arthritis. Several prominent personalities touted the drug as a COVID-19 treatment since the onset of the pandemic, most notably former U.S. President Donald Trump. However, public health officials, including Fauci, warned that there wasn’t evidence to support the use of hydroxychloroquine as a COVID-19 treatment.

The 2003 report cited by Rose hypothesized that the anti-inflammatory effect of chloroquine and hydroxychloroquine could be beneficial to patients^[8]. As this USA Today fact-check and a previous Health Feedback review reported, there is no evidence that hydroxychloroquine is effective in the treatment of COVID-19.

Several clinical studies and one systematic review concluded that the use of this drug isn’t beneficial for treating COVID-19^[9,10,11]. Furthermore, its use for the treatment of COVID-19 has been associated with serious side effects, like cardiotoxicity^[12]. One trial found that the use of hydroxychloroquine was associated with increased mortality in COVID-19 patients^[13].

Although the FDA issued an Emergency Use Authorization (EUA) for chloroquine and hydroxychloroquine as COVID-19 treatment in March 2020, the EUA was later revoked in June 2020, based on new scientific evidence that these drugs are unlikely to be effective in treating COVID-19 In July 2020, the FDA warned about the use of these drugs in COVID-19 patients, due to safety concerns including “blood and lymph system disorders, kidney injuries, and liver problems and failure”.

The WHO also discontinued the clinical trials studying hydroxychloroquine as a COVID-19 treatment, which were conducted as part of the Solidarity Trial, as no benefit had been found related to the use of this drug in COVID-19 patients.

There is also no evidence that hydroxychloroquine has been used successfully in India to stop the spread of COVID-19, contrary to Rose’s claims. Overall, there is no evidence that hydroxychloroquine is effective in treating COVID-19. At the same time, its use carries some risk for COVID-19 patients. Rose and Clark’s claim that hydroxychloroquine is effective at treating COVID-19 is unsupported by scientific evidence.

Conclusions

As shown above, several of the claims made in the viral video about the Health and Freedom Conference are inaccurate, misleading, or unsupported by evidence. The prediction of 2.2 million deaths from COVID-19 in the U.S. was based on the assumption that no measures were taken to curb the spread of the disease, while in the real world, measures were indeed taken to reduce the spread of COVID-19. Therefore, it is inaccurate and misleading to claim that this prediction was deliberately false simply because the projected and actual death toll aren’t the same.

The aim of the WHO information notice was to remind users to adhere to manufacturers’ instructions for using PCR tests and to be careful when interpreting test results. The speakers didn’t provide any evidence demonstrating that PCR results are mostly or all false positives, as they implied. The PCR tests are a reliable way to detect SARS-CoV-2, with high sensitivity and specificity.

Finally, there is insufficient evidence supporting the claim that budesonide is effective for treating COVID-19. Its potential side effects in COVID-19 patients are unknown and further research on its benefits is required. As with budesonide, hydroxychloroquine hasn’t been found to produce beneficial effects in COVID-19 patients and is also associated with a risk of side effects like heart damage. In the absence of evidence demonstrating their benefit and the presence of evidence for harm, the use of these drugs to treat COVID-19 isn’t recommended, except in clinical trials designed to assess their effectiveness.

REFERENCES

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• 2 – Ferguson et al. (2020). Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand. Imperial College London.
• 3 – Rice et al. (2020). Effect of school closures on mortality from coronavirus disease 2019: old and new predictions. BMJ. 
• 4 – Haug et al. (2020). Ranking the effectiveness of worldwide COVID-19 government interventions. Nature Human Behaviour.
• 5 – Hwang (2021). Coronavirus lockdown and virus suppression: An international analysis. Technological Forecasting and Social Change.
• 6 – Ramakrishnan et al. (2021). Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. The Lancet Respiratory Medicine.
• 7 – Agusti et al. (2021). Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19. The Lancet Respiratory Medicine.
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• 9 – Ebina-Shibuya et al. (2021). Hydroxychloroquine and chloroquine for treatment of coronavirus disease 19 (COVID-19): a systematic review and meta-analysis of randomized and non-randomized controlled trials. Journal of Thoracic Disease.
• 10 – Elavarasi et al. (2020). Chloroquine and Hydroxychloroquine for the Treatment of COVID-19: a Systematic Review and Meta-analysis. Journal of General Internal Medicine.
• 11 – Horby et al. (2020). Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. The New England Journal of Medicine. 
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• 13 – Axfors et al. (2021). Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature Communications.