The researchers discuss the possibility that Zika may spread through contact with tears of sweat from a highly infectious patient.
The first patient, a 73-year-old man, died in June of this year at the University of Utah hospital in Salt Lake City - the first known case of Zika virus-related death in the continental U.S.
He began experiencing symptoms of Zika virus infection 8 days after returning from a trip to southwest Mexico, a Zika-infected area.
At first, his symptoms were abdominal pain and fever. By the time he was admitted to the hospital, he also had watery, inflamed eyes, low blood pressure, and a rapid heart rate. He developed septic shock, his kidneys, lungs, and other organs shut down, and he died shortly after.
The second patient, "a previously healthy 38-year-old man with no known coexisting illnesses," visited the first patient in hospital and reported wiping away his tears and helping nurses to reposition him in the hospital bed.
He came to the attention of one of the authors during a discussion about what happened to the first patient a week after he died; they noticed he had red, watery eyes, a common symptom of Zika infection.
Tests confirmed the second patient was infected with Zika, but his symptoms were only mild and resolved within a few days.
Case continues to puzzle health experts
Two aspects of this case continue to puzzle health experts. First, why did the first patient die? It is very rare for Zika infection to even cause severe illness in adults - much less, death.
Fast facts about Zika
- Health authorities say the best way to prevent Zika is to prevent mosquito bites
- Pregnant women are advised not to travel to areas with Zika
- Couples with a partner who lives in or has been to a Zika area should take protective measures during sex.
Only nine other cases of deaths linked to Zika virus have been reported worldwide, note the researchers from the University of Utah School of Medicine, together with colleagues from ARUP Laboratories, also in Salt Lake City.
The second point that remains a mystery is how did the second patient contract Zika? He did nothing that was known at the time to put himself at risk.
In their letter, the researchers suggest unusually high levels of Zika virus in the first patient's blood may have been the cause of his death.
This may also explain why the second patient may have become infected with the virus - through touching tears or sweat from the first patient. The authors note this is the first time such a transmission route has been documented.
Corresponding author Sankar Swaminathan, a professor of internal medicine at the University of Utah School of Medicine, remarks:
"This rare case is helping us to understand the full spectrum of the disease, and the precautions we may need to take to avoid passing the virus from one person to another in specific situations."
'Viral load 100,000 times higher'
The researchers ran several tests to show there were no other infections that could explain the first patient's illness. One of these is called Taxonomer, which rapidly analyzes all genetic material from infectious agents in a patient's sample.
They found the Zika virus the first patient was infected with was 99.8 percent identical to that identified in a mosquito collected from the area he had visited - southwest Mexico - in the weeks before falling ill.
In discussing how the second patient became infected, the authors note that the species of mosquito that carries Zika has not been found in Utah, he had not traveled to a Zika-infected area, and a reconstruction of events ruled out any other known means of transmission.
The researchers suggest the reason the second patient become infected was because the first patient had unusually high levels of virus in his body - 200 million particles per milliliter. This could have overwhelmed his system and made him extremely infectious.
Prof. Swaminathan, who is also chief of infectious diseases at the School of Medicine, describes his reaction:
"I couldn't believe it. The viral load was 100,000 times higher than what had been reported in other Zika cases, and was an unusually high amount for any infection."
The researchers say they still do not know what led to such an unusually severe infection. Did something in the first patient's biology or health history make him particularly vulnerable? Was the particular strain he had - there were tiny genetic differences to other known strains - particularly aggressive?
Prof. Swaminathan says we may never see another case like this, and it shows we still have a lot to learn about Zika.
"This type of information could help us improve treatments for Zika as the virus continues to spread across the world and within our country."
Prof. Sankar Swaminathan