Two Twins, Different COVID-19 Trajectories

Jake Remaly

December 15, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Twin brothers in Italy developed symptoms of COVID-19 on the same day in March. Given their shared genetic background and similar presentations, doctors believed they would have a similar clinical course.

Instead, one had a 12-day hospital stay and recovered uneventfully, while the other developed critical disease and required mechanical ventilation. The brother with more serious illness was in the hospital 22 days longer and slowly recovered after hospitalization.

Davide Lazzeroni, MD, from Fondazione Don Carlo Gnocchi in Parma, Italy, and colleagues described the cases in a letter published December 8 in the Annals of Internal Medicine.

The reason for the different illness trajectories is a mystery. Physicians and researchers have speculated on the journal's website and on social media about possible explanations, such as unexplored differences in the gut microbiome or initial viral load.

Same Age, BMI, Address

The brothers were 60 years old and considered homozygous twins because of their appearances and characteristics. Neither had a history of chronic disease or cardiovascular risk factors. Each had a body mass index (BMI) of 26.

After 10 days of symptoms, including fever, nasal congestion, fatigue, dyspnea, and dry cough, the twins were hospitalized with mild interstitial pneumonia.

Both received supplemental oxygen, paracetamol, hydroxychloroquine, darunavir/cobicistat, and enoxaparin at prophylactic dosages from the same medical team.

The brother with milder illness was discharged without complications. In contrast, his twin "had a progressive increase in leukocyte count and C-reactive protein level associated with a variable increase in body temperature," the authors reported. "Moreover, noninvasive ventilation was necessary.... After 3 days of ineffective ventilation, he was transferred to the intensive care unit [ICU] where he...was intubated and mechanically ventilated. He developed septic shock from an anaerobic bacterial infection that required vasopressors, antibiotics, steroids, and 4 days of invasive ventilation."

Seventeen days of uncomplicated hospitalization followed the ICU stay. His recovery after hospitalization was slow, "but ended in full recovery of gas exchange without long-term consequences," the authors write.

The report identified at least one baseline difference: the patient with milder illness was married, whereas his brother was not. But there were more shared traits, too.

"They lived at the same address and worked at the same location repairing automobiles in a body shop," the authors noted. "Contact tracing identified 1 of their customers...as the likely source of their infections.... We also know that the number of polymerase chain reaction cycles needed to produce detectable viral RNA was similar, which suggests that the viral load at diagnosis was similar."

Furthermore, the twins had the same vaccination schedule and similar dietary habits, said Lazzeroni and coauthors Pietro Concari, MD, from Suzzara Hospital in Mantova, and Luca Moderato, MD, PhD, from Guglielmo da Saliceto Hospital in Piacenza, both in Italy, in an email to Medscape Medical News.

Further Research

"We hope the further investigations (genetic, epigenetic, metabolic, immunological, and microbiological) that we will perform on the two twins may have translational repercussions to improve the knowledge of COVID-19 pathophysiologic mechanisms," they said. "There is still a long way to understand the prognostic factors of COVID-19."

The cases suggest that genetics are not necessarily behind differences in COVID-19 severity, they added.

Although the report is important to consider, the lack of a DNA test to establish the twins' monozygosity is problematic, commented Nancy L. Segal, PhD, professor of psychology and director of the Twin Studies Center at California State University, Fullerton.

"That being said, if we assume that the twins are monozygotic (or identical), there are many factors that could explain their discordance," Segal said. "In fact, monozygotic twins are less alike than people think they are, but still more alike than any other pair of people."

For example, concordance rates for schizophrenia and diabetes are about 40% and 50%, respectively, she said.

Exposure to different forms of the virus, birth weight differences that reflect in utero differences, spontaneous mutation in COVID-relevant genes, and exposure to nonshared environments that affect immune response are variables that could play a role, said Segal, who has written books about twins. "However, until the zygosity (twin type) of the pair is scientifically confirmed, interpreting these results hangs in the balance."

Ann Intern Med. Published online December 8, 2020. Abstract

The study authors and Segal have disclosed no relevant financial relationships.

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