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Clinical Laboratories Should Anticipate Gender-Dependent Differences in COVID-19 Antibody Levels, New Study Suggests

Clinical laboratories and meta-analysis recently published casts doubts on serology test performance, Abbott antigen test
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As COVID-19 antibody testing becomes more popular, it is important to recognize that results may vary based on gender, with higher levels and longer duration in men

Much of COVID-19 testing since the start of the global pandemic has focused on diagnostic testing. Over the past year, clinical laboratories have experienced a tremendous demand for COVID-19 PCR and antigen testing by people who suspected they had an active COVID-19 infection or by those who needed confirmation they were not infected.

While diagnostic COVID-19 testing has created an unprecedented demand for laboratory testing, COVID-19 antibody testing has not enjoyed the same demand. In the early days of the pandemic, many laboratory experts anticipated that antibody testing demand would quickly grow as people wanted to understand if they had previously been infected or had developed an immunity to COVID-19.

New Surge of Interest in COVID-19 Antibody Testing

Demand was initially projected to grow for antibody testing, however, research indicated that COVID-19 antibody levels only lasted for a few months, and it has continued to be unclear exactly how COVID-19 immunity develops. There has also been little research on how effective innate immunity is at preventing future COVID-19 infections and surprisingly little interest in if and how this natural immunity develops.

Even though the initial interest in antibody testing was not as high as anticipated, in recent weeks antibody testing gained new attention. Ortho Clinical Diagnostics has recently signed a $53 million deal with the federal government that triples their test production capabilities, and Ortho specifically identified their two antibody tests as an area of production they would increase. The US Food and Drug Administration (FDA) also just approved the first ever at-home collected antibody test. These and other signs indicate that antibody testing may be an upcoming trend.

As antibody testing is seeing a renewed surge in interest, a new study has suggested that antibody levels may vary based on gender. A study published in the Annals of Epidemiology and Public Health shows that COVID-19 antibody body levels are significantly higher in males and that antibodies may last for four times longer in males.

Jessica Williams PhD Cardiff Met antibody testing
Jessica Williams, PhD, studies COVID-19 antibody levels, comparing levels in males and females over time. Says Williams, who also researches cardiovascular metabolism and inflammation at Cardiff Metropolitan University in the UK, continued COVID-19 antibody testing reveals new insights. (Photo source: Cardiff Metropolitan University)

Research into COVID-19 Antibody Gender Differences Explained

“We know that the production of protective antibodies following an infection forms the basis of immunity,” Jessica Williams, PhD, the study’s lead author, said in a recent article. “While its clear that infection with the coronavirus results in antibody production, we arent sure of the amounts of antibodies produced, how long they last, or whether they protect people from getting COVID-19 again.”

Continued Williams, “Our study didnt find a statistically significant difference in the number of men and women who had antibodies, however, when we compared antibody levels in those who tested positive, we did find a key difference: male participants’ levels were three times those of female participants. This was despite there being no difference in the previous COVID-related symptoms reported by men and women—suggesting no difference in the severity of the infections that produced them.”

Continued COVID-19 Antibody Testing May Reveal New Information

While COVID-19 antibody levels were significantly higher in men, continued research also elucidated differences in the durations of antibody levels. “When we followed up with a second test three months later, we found another key difference,” Williams expounded. “Of those who had previously had antibodies against COVID-19, 21.7% no longer tested positive, implying that one in five asymptomatic people who generate antibodies against COVID-19 lose these after six months.

“Interestingly, 80% of those who had lost their antibodies in our study were women,” Williams continued. “The women who had lost their antibodies were also on average ten years older than women who retained antibodies. This may be related to an altered immune response in women who are approaching menopause or are post-menopausal, similar to that seen in the flu.”

Ultimately, Williams says that clinicians should anticipate that antibody level findings may not be homogenous. “Altogether, our results suggest that as we assess immunity to COVID-19—and its longevity—we need to be prepared for it not to be uniform. Age and sex could result in important differences.”

Clinical laboratories should be aware of the potential for quantitative differences in COVID-19 antibody levels, especially as an increased demand for antibody testing may be developing. By understanding the potential for gender-based differences in antibody levels, clinical laboratory professionals can better inform their patients and guide clinicians who are ordering these tests.

—By Caleb Williams, Editor, STAT Intelligence Briefings

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