Study of the 50 Omicron variants could lead to new approaches to clinical laboratory testing and medical treatments for long COVID
Patients infected with SARS-CoV-2 can usually expect the COVID-19 illness to subside within a couple of weeks. However, one Dutch patient remained infected with the coronavirus for 612 days and fought more than 50 mutations (aka, variants) before dying late last year of complications due to pre-existing conditions. This extreme case has given doctors, virologists, microbiologists, and clinical laboratories new insights into how the SARS-CoV-2 virus mutates and may lead to new treatments for long COVID.
The medication the patient was taking for his pre-existing conditions may have contributed to his body being unable to produce antibodies in response to three shots of the Moderna mRNA COVID vaccine he received.
Magda Vergouwe, MD, PhD candidate at the Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, who lead a study into the patient, theorized that some of the medications the patient was on for his pre-existing conditions could have destroyed healthy cells alongside the abnormal cancer-causing B cells the drugs were meant to target.
“This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals,” the researchers said prior to presenting their report about the case at a meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Barcelona, Spain, Time reported. “We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections.”
“Chronic infections and viral evolution [are] commonly described in [the] literature, and there are other cases of immunocompromised patients who have had [COVID] infections for hundreds of days,” Magda Vergouwe, MD, PhD candidate (above), Center for Experimental and Molecular Medicine at Amsterdam UMC, told Scientific American. “But this is unique due to the extreme length of the infection … and with the virus staying in his body for so long, it was possible for mutations to just develop and develop and develop.” Microbiologists, virologists, and clinical laboratories involved in testing patients with long COVID may want to follow this story. (Photo copyright: LinkedIn.)
Risks to Immunocompromised Patients
Pre-existing conditions increase the risk factor for COVID-19 infections. A 2021 study published in the Journal of the American Board of Family Medicine (JABFM) titled, “Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19,” found that about 61% of that study’s test group had a pre-existing condition prior to the outbreak of the COVID-19 pandemic.
When the Dutch man was admitted to Amsterdam UMC with common and serious COVID-19 symptoms, such as shortness of breath, a cough, and low blood oxygen levels, he was prescribed sotrovimab (a monoclonal antibody) along with other COVID treatments.
About a month after being admitted his COVID-19 symptoms decreased, so he was first discharged to a rehab facility and then finally to his home. However, he continued to test positive for the coronavirus and developed other infections that may have been complicated by the persistent case of COVID-19.
The Amsterdam UMC doctors emphasized that the man ultimately succumbed to his pre-existing conditions and not necessarily COVID-19.
“It’s important to note that in the end he did not die from his COVID-19,” Vergouwe told Scientific American. “But he did keep it with him for a very long period of time until then, and this is why we made sure to sample [the virus in his body] as much as we could.”
One in Five Adults Develop Long COVID
Long COVID does not necessarily indicate an active infection. However, in as many as one in five US adults COVID symptoms persist after the acute phase of the infection is over, according to a study published recently in JAMA Network Open titled, “Epidemiologic Features of Recovery from SARS-CoV-2 Infection.”
“In this cohort study, more than one in five adults did not recover within three months of SARS-CoV-2 infection. Recovery within three months was less likely in women and those with pre-existing cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave,” the JAMA authors wrote.
The origins of long COVID are not entirely clear, but according to the National Institutes of Health (NIH) it can develop when a patient is unable to sufficiently rest while battling off the initial virus. According to Vergouwe, the SARS-CoV-2 genome will always grow quicker when found in a patient with a compromised immune system.
Unique COVID-19 Mutations
More than 50 new mutations of the original Omicron variant were identified in the Dutch patient. According to Vergouwe, “while that number can sound shocking, mutations to the SARS-CoV-2 genome are expected to evolve more quickly in those who are immunocompromised (the average mutation rate of the virus is estimated to be two mutations per person per month),” Scientific American reported. “What does make these mutations unusual, she noted, is how their features differed vastly from mutations observed in other people with COVID. [Vergouwe] hypothesizes that the exceptional length of the individual’s infection, and his pre-existing conditions, allowed the virus to evolve extensively and uniquely.”
COVID-19 appears to be here to stay, and most clinical laboratory managers and pathologists understand why. As physicians continue to learn about the SARS-CoV-2 coronavirus, this is another example of how the knowledge about SARS-CoV-2 is growing as different individuals are infected with different variants of the virus.
About half of nearly 7,000 respondents admitted to sloppy practices, which suggests that pathologists and clinical lab professionals may want to be skeptical about the findings of many papers published in medical journals
It may surprise pathologists and medical laboratory professionals to learn that as many as 10% of surveyed authors of published scientific papers admitted to regularly falsifying or fabricating data! This was one finding in a study conducted by researchers to determine the quality and accuracy of scientific papers that are published in journals.
In its coverage of the NSRI’s findings, Nature wrote, “Between October and December 2020, study authors contacted nearly 64,000 researchers at 22 universities in the Netherlands, 6,813 of whom completed the survey.”
According to Nature, “An estimated 8% of scientists who participated in an anonymous survey of research practices at Dutch universities confessed to falsifying and/or fabricating data at least once between 2017 and 2020. More than 10% of medical and life-science researchers admitted to committing this type of fraud, the survey found.”
Gowri Gopalakrishna, PhD, an epidemiologist and public health policy scientist with the Amsterdam University Medical Center (AUMC) who helped lead the NSRI study “thinks that the percentage of researchers who confessed to falsifying or fabricating data could be an underestimate,” Nature reported.
Thousands of Researchers Admit to ‘Questionable Research Practices’
Conducted online, the NSRI received responses from nearly 7,000 academics and researchers across a wide range of disciplines. About half admitted to engaging in “questionable research practices” (QRPs), 4.3% admitted to fabrication of data, and 4.2% admitted to falsification of data.
The NSRI presented its survey results in two preprints:
The NSRI study authors wrote that QRPs included “subtle trespasses such as not submitting valid negative results for publication, not reporting flaws in study design or execution, selective citation to enhance one’s own findings and so forth.”
Survey organizers originally sought responses from more than 60,000 researchers, but “many institutions refused to cooperate for fear of negative publicity,” Science reported.
The authors cited “publication pressure,” otherwise known as the “publish or perish” reward system, as the top factor driving questionable research practices. Respondents were “less likely” to engage in questionable research practices, data falsification, or fabrication if they subscribed to scientific norms and perceived a high likelihood of being detected.
According the NSRI findings, within academic ranks, PhD candidates and junior researchers were “most likely” to engage in QRPs, as well as males and people involved in empirical research.
Epidemiologist Gowri Gopalakrishna, PhD (above), a post-doctoral researcher and the project secretary for the NSRI, told Science that advocates for research integrity should pay more attention to “sloppy research practices” as opposed to outright misconduct. “We need to have a positive environment where mistakes can happen, and where there is more focus on responsible conduct, slower science, and taking time for good quality research,” she said. Clinical laboratory professionals would likely agree with Gopalakrishna’s assessment. (Photo copyright: University of Amsterdam Medical Center.)
Tracking Retractions
Retraction Watch, a blog founded in 2010 by medical journalists Ivan Oransky, MD, and Adam Marcus, offers a day-to-day barometer on research integrity. As the name indicates, the blog tracks research studies that have been retracted due to scientific misconduct or other reasons. In 2018, the bloggers launched a searchable database with more than 18,000 papers or conference abstracts that had been retracted.
An analysis by Science, titled, “What a Massive Database of Retracted Papers Reveals about Science Publishing’s ‘Death Penalty’,” looked at about 10,500 retracted journal articles in the database. It found that about half of those retractions involved scientific misconduct, including fabrication, falsification, and plagiarism. Nearly 40% were withdrawn “because of errors, problems with reproducibility, and other issues,” the analysis noted.
The data also indicates that a relatively small number of authors—about 500—accounted for about 25% of the retractions in journals.
In addition to the blog, Oransky and Marcus penned a column for STAT, titled, “The Watchdogs” in which they called attention to scientific misconduct and suggested solutions. Some solutions included:
Use of statistical analysis to identify data fabrication in advance of publication.
Tips From a Media Watchdog
Gary Schwitzer, founder and Publisher of HealthNewsReview.org, a media watchdog website, offers additional insights. Schwitzer is a longtime medical journalist who also taught health journalism and media ethics at the University of Minnesota.
“Not all studies are the same and no study should necessarily be equated with the truth,” Schwitzer said in a video embedded on the website. People “often lose sight of the fact that journals were meant to be forums for discussions among scientists, not a source of daily news.”
The website also includes a tip sheet for evaluating claims about medical tests.
The NSRI’s research is the latest in a long line of studies into so-called “scientific research,” some of which found “cooked” data and outright fraud. This suggests that pathologists and clinical laboratory professionals should follow the saying caveat emptor (“Let the buyer beware”) when absorbing research published in scientific journals or presented at meetings.
