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From Brief19: CDC Begins Search For The True Denominator

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April 8, 2019

The Centers for Disease Control and Prevention (CDC) has announced that it will begin an attempt to determine how many total people in the United States have been infected by the SARS-CoV-2 virus. Because of inadequate testing and symptom-free patients, many people are unaware that they were ever infected.

The agency will analyze blood from people who were not diagnosed but live in “hot spots” to see how widely the virus circulated. Another part of the study will assess blood samples from all over the country, in a similar effort. A third component will focus on special populations, with a priority on healthcare workers. If this work is successful, it may help the CDC plan for future SARS-CoV-2 surveillance.

The study will also help to provide a more accurate assessment of morbidity and mortality rates related to the infection.

Shared with permission from Brief19, a daily review of #covid-19 research and policy.

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\ \ April 14, 2020\ In a preprint of a randomized clinical trial posted in medRxiv, researchers in Brazil randomized patients to receive either the anti-malarial drug chloroquine (CQ) 600mg twice daily for ten days or 450mg low dose CQ for five days.\ Compared to low-dose CQ, patients receiving high dose CQ had more adverse cardiac effects (25 percent of patients’ hearts began to have abnormally long recovery times between beats, known as a “long QTc interval”) and even increased mortality (17 percent). When the researchers compared the patients in this study to those who had not received CQ, fatality rates were similar suggesting that the effects of CQ for covid-19 are negligible. It is important to note that only half of the patients assessed had laboratory-confirmed SARS-Cov-2 infection. The other half had the “covid-19” syndrome, which was not confirmed by labs but, rather, by physicians’ suspicion only.\ Analysis: This “preprint publication” has not been peer-reviewed by experts. Other considerations: 1) These patients were also taking azithromycin, an antibiotic which, like CQ, is known to increase the QTc interval of the heart. So, the potentially dangerous cardiac side effect of CQ seen here may be synergistic with azithromycin. 2) It is possible that some of the patients without laboratory confirmed SARS-Cov-2 may have had viruses other than SARS-CoV-2. That said, despite some limitations, this is the first randomized clinical trial of CQ. These “negative results” are not unexpected. Randomized trials frequently deliver disappointing results for medications that have “anecdotal evidence showing promise” for a disease. This study casts serious doubt as to the effectiveness of CQ for treating covid-19.\ Worse, the results of this study provide some evidence that CQ (and its cousin hydroxychloroquine) might be harmful while not offering any help to covid-19 patients. Though many hospitals continue to use these medications, there remains no compelling evidence to support the routine use of CQ or hydroxychloroquine for treating covid-19 infection.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/48f62049-d39a-471c-89b3-01c390abcef9)

\ \ March 30, 2020\ A not yet peer-reviewed manuscript from the University of Nebraska Medical Center provides evidence of viral contamination in commonly used items, toilet facilities and air samples. Researchers studied thirteen covid-19 patients who were housed in the National Biocontainment Unit and National Quarantine Unit. All rooms were “negative pressure” rooms, which draw air in but not back out. In the study, cell phones (83%) were identified as substantial sources of contamination. Other contaminated sources included glasses and stool samples from toilets (of which 81% were positive for SARS-Cov-2). But most concerning is that SARS-Cov-2 particles were found in the air even at distances greater than six feet from patients and were found in the ambient air even when patients who were not coughing. Nasal oxygen tubes (cannulas), a device commonly used in hospitals was found to distribute the highest airborne concentrations of SARS-Cov-2. Although these are preliminary findings from only thirteen patients held in isolation, it is concerning that the SARS-Cov-2 virus may be aerosolized even in mildly ill patients, and without the provocation of so-called aerosolizing procedures (such as suctioning) which cause viral particles to be carried, briefly, in droplets in the air. While it is uncertain still how much is “too much” of the virus for an individual to inhale come in contact with, this study underscores the need for healthcare providers to wear the appropriate PPE around patients under investigation and covid-19 positive patients.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/4d4855c2-c3ac-43c9-9276-5cda22546a19)

\ \ April 6, 2020\ In a paper published in the preprint journal medRxiv, researchers in Wuhan, China analyzed medical records of patients hospitalized with confirmed SARS-CoV-2 infection. They separated patients with both covid-19 and high blood pressure (hypertension) into two groups: patients who had been prescribed the antihypertensives “ACE inhibitors” and “ARBs,” and patients who had not been prescribed either of these medications. The question: do ACE inhibitors or ARBs have any effect, good or bad, on covid-19 infection? As previously covered in Brief19, experts have debated the use of these medications.\ In this new study, researchers found that patients taking ACE inhibitors and ARBs were much less likely to develop “very severe” covid-19, and also had lower death rates. Does this mean that patients who have their elevated blood pressure under control have a better chance at good outcomes? It’s possible. High blood pressure appears to be a risk factor for poorer outcomes. Alternatively, might these medications even actively interrupt the virus’ attempt to enter cells, as we have covered? Too soon to say. However, these data do provide some preliminary evidence that patients already taking either an ACE inhibitor or an ARB for high blood pressure may not need to stop taking these medications if they become infected with SARS-CoV-2, as some experts have suggested might be necessary.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/53f2dc7d-ec1f-480f-9059-f925f2fdc11d)

\ \ May 29, 2020\ Editor's note: Yesterday a group of concerned scientists issued an open letter with concerns regarding a recent study of hydroxychloroquine published last week in The Lancet, and covered here in Brief19. The letter, signed by 120 researchers all over the world, alleges that the study has irregularities that may suggest research misconduct. Problems identified include more patients from certain hospitals than are known to have been treated at such facilities and dosing problems. If the paper were to be retracted, it could be seen as a major setback for those seeking to stop hydroxychloroquine proponents from advancing the use of a medication not proven to benefit patients with covid-19. It was in part based upon this study (which described poorer outcomes amongst patients who received hydroxychloroquine). While the study was "observational," and thus cannot be used to imply a cause-and-effect, the fact that there were 96,032 patients included in the analysis impressed many observers. Regardless of the outcome of any investigation that may stem from this open letter, to date, no high-quality study has demonstrated that hydroxychloroquine helps patients with SARS-CoV-2.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/6e9e8e3b-ddf5-4769-943e-84f369a93ad4)

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