An 11-year-old boy was in a hospital in Belgrade with a cough and fever. Doctors said he may have been exposed to tuberculosis, but he was more concerned about something else they said. One of the patients there was feared to be positive for smallpox. It was 1972 and Yugoslavia was experiencing Europe’s last major outbreak of the dreaded disease.
that boy was Janko Nikolich-Žugich, MD, PhD, who was never sure whether he had ever had tuberculosis – he was still being treated for it – or whether the other patient actually had smallpox. But experiencing an epidemic in his early years sparked an interest in infectious diseases in Dr. Nikolich-Žugich, an internationally recognized immunologist and gerontologist at the University of Arizona Health Sciences.
“Infections have shaped our civilization more than anything,” says Dr. Nikolich, chief of the UArizona College of Medicine – Tucson’s Department of Immunobiology and co-director of the Arizona Center on Aging. “Our relationship with microbes is in many ways still one of the most critical relationships we have in this world.”
Build a career in the fight against infection
Dr. Nikolich’s decision to pursue a healthcare career wasn’t just influenced by his childhood illness: his father, grandfather, and grandmother were all doctors. He followed in their footsteps and obtained a medical degree and a doctorate in immunology from the University of Belgrade. While completing his compulsory military service from 1986 to 1987, he spent most of his time providing medical treatment to the troops and their families.
When Dr. Nikolich returned to a civilian career, he decided to emigrate to the United States, where opportunities to conduct serious research were plentiful. He began as an assistant professor at the Sloan-Kettering Institute for Cancer Research and in the Division of Molecular Medicine at Cornell University School of Medicine and worked his way up to a senior scientist position in the Vaccine and Gene Therapy Institute at Oregon Health and Science University. .
In 2008, he joined the University of Arizona Health Sciences, where he continues to make discoveries and advances in immunity and infection in older adults. His research focuses on persistent viruses, including cytomegalovirus, a herpes virus that can lie dormant in the cells of a person’s body before being reactivated later in life.
“That process of awakening or reactivating the viruses may have a greater impact on us, or a lower impact on us, depending on our age and condition,” said Dr. Nikolich.
He has spent a significant portion of his career investigating outbreaks of various viruses. He has studied several annual flu outbreaks and the mosquito-borne Chikungunya virus and West Nile virus. The latter caused the largest recognized epidemic of neuroinvasive arthropod-borne viral diseases in the Western Hemisphere in 2002. Around the same time, his lab was getting ready to study Severe Acute Respiratory Syndrome, or SARS, a viral respiratory disease caused by a coronavirus. While he didn’t end up working with that particular coronavirus, the preparation was helpful when SARS-CoV-2 came around.
“Science forces you to do new things all the time,” he said. “Biology will always have surprises for you. The more you’ve read about things in the past without even knowing it’s going to be useful, that remembering becomes really crucial.
Tackling the new coronavirus
dr. Nikolich’s decades of research into the immune system, infections and aging uniquely prepared him to face major challenges as the COVID-19 pandemic began.
“Science forces you to do new things all the time. Biology will always bring surprises.”
Janko Nikolich-Žugich, MD, PhD
When the mysterious SARS-CoV-2 virus spread in early 2020, he teamed up with Deepta Bhattacharya, PhD, professor in the Department of Immunobiology and member of the BIO5 Institute, to create one of the most accurate antibody tests in the world. Accuracy is paramount when dealing with such a widespread virus.
“We needed something that would be much more than 99% accurate,” said Dr. Nikolich, who is also a member of the BIO5 Institute.
The test is so accurate because it recognizes antibodies made in response to two independent parts of the virus’s spike protein. It only gives a positive result if there are antibody signals for both components. Having a highly accurate antibody test gave the team more concrete evidence of past infections and gave more insight into how long the antibody immunity might last. They were among the first to publish research on long-term immunity to COVID-19.
Pandemic strikes close to home
dr. Nikolich was in Serbia with his parents when the coronavirus began to march through Europe in March 2020. He doubts he wore a mask on the plane home because no one knew how the virus spread. Less than a year later, he boarded the plane again – this time double-masked – to visit his 97-year-old father, who had been diagnosed with COVID-19.
“He fought well against the virus. He’s fired up some pretty impressive antibody titres,” he said. “He never really developed complete respiratory distress, but his body couldn’t handle it. He just stopped eating.”
In late 2020, COVID-19 claimed the life of Zarko Nikolic, MD.
“I was there to direct his care and make sure he was comfortable,” said Dr. Nikolich. “And that was a blessing.”
His mother, Mirjana Nikolic, died almost two years later. Consequences of a previous COVID-19 infection were likely a contributing factor. dr. Nikolich said his passion for fighting COVID-19 was there before his parents died, but he shares the pain millions have felt from losing a loved one during the pandemic.
“My lab studies the decline of immunity in older adults. When a virus like this strikes, we need to do some research and try to understand it. One fact that people may not realize is that people over the age of 80 died 270 times higher from COVID-19 than people between the ages of 18 and 39,” he said. “That’s not 270% anymore, that’s 270-fold. That means that for every person between the ages of 18-39 who died, more than 270 people over the age of 80 died, which is a staggering number.”
Preparing for the future
Today, Dr. Nikolich unraveling the mysteries of the human immune response to COVID-19. Some of the research takes place through the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) initiative, which has long been studying COVID. dr. Nikolich leads the Arizona Post-SARS-CoV-2 Cohort Consortium (AZP3C), a statewide partnership of six institutions supported by the RECOVER Clinical Science Core at New York University Langone Health.
To study the long-term effects of COVID-19, the AZP3C team will recruit individuals who have experienced COVID-19 or are in the acute phase, including adults from vulnerable, elderly and disadvantaged populations and representing different races and ethnicities.
dr. Looking beyond COVID-19, Nikolich, as director of the Aegis Consortium, a UArizona Health Sciences initiative, brings together a team of experts to devise solutions for the next pandemic.
The focus of the Aegis Consortium is on forecasting and preparedness, the acute and long-term effects of pandemics on individuals and societies, and the use of built and natural environments in pandemic management. The three-pronged approach is designed to identify mechanisms and strategies to prevent new pandemics.
“We know a lot about the coronavirus and COVID-19, but there is still more to learn,” said Dr. Nikolich. “Unfortunately, we also know that this will not be the last pandemic we see. The Aegis Consortium brings together experts in research, technology and innovation to develop solutions that protect the world from future pandemics.”