It was a potentially lethal form of strep A.

“We were very surprised,” Myers said. “We just don’t see this many together in such a short time.”

Infection with Streptococcus pyogenes — or group A strep, for short — typically produces mild symptoms, such as rash, fever or swollen tonsils leading to the eponymous strep throat. But in recent months, cases related to a rare invasive form of the common bacteria have been popping up across the United States, as well as Europe, often in connection with sometimes confusing symptoms, including skin rashes, fever, a racing heart and unexplained swelling.

The first confirmed pediatric deaths in this country, in two young children in the Denver area, were reported last week. At least 16 children have died of it in the United Kingdom, seven in the Netherlands and two in France.

The rise of invasive strep A is one of a number of unusual ways pathogens have been interacting with us — and each other — amid the end of coronavirus-era social distancing and masking this year. Both the World Health Organization and the U.S. Centers for Disease Control and Prevention said they are investigating the cases, including whether the viral storm that has been keeping many people sick may be at least partially to blame.

Why a ‘tripledemic’ is keeping some people sick for weeks, even months

Viral infections tend to create disorder in a person’s immune system, making it easier for a secondary bacterial infection to take hold and intensify its effects in some cases.

Minnesota health officials said they had seen 46 cases of invasive strep A in all ages in November, more than double the average 20 cases in previous months. Colorado reported that it was investigating not only a rise in invasive strep A cases, but also a possible increase in other severe or invasive bacterial infections in children.

Texas Children’s Hospital said it has seen more than 60 patients with invasive strep A in October and November — a fourfold increase from the same period the previous year. James Versalovic, pathologist-in-chief for the medical center, said many of the affected children had current or recent viral infections. But, he said, it is still too early to rule out other factors that may be contributing to the seriousness of their illnesses.

“It could be we have altered patterns of immunity due to the pandemic that may have increased our vulnerability. But it could also be … different variants” of strep, he said. “It could be a combination of factors. No one knows.”

Unlike SARS-CoV-2, strep A is something humans have battled for centuries.

It has variously been described, incorrectly, throughout history as being associated with phenomena such as comets and eclipses, or the introduction of nonliving matter into humans. It wasn’t until 1874 that Austrian surgeon Theodor Billroth described an organism he saw under a microscope that appeared to be grouped in chains of four or more that would later be classified as bacteria. Bacteria can live in or out of a patient’s body, unlike viruses, which are a collection of molecules that can only replicate in a host. Both are transmitted in similar ways — through air, water, food and living things.

Several million people in the United States are infected each year with strep A, and in our modern world, with its ample supply of antibiotics, it is mostly a nuisance. It usually translates into a sore throat, and maybe a missed day of school or work during the 24 hours it takes to stop being contagious after taking antibiotics such as penicillin and amoxicillin.

Strep A: What you need to know about the usually mild infection

“The good news is that we know how to treat it and how to test for it,” said Kristin Moffitt, an infectious-disease expert at Boston Children’s Hospital who studies bacterial infections. “Normally it’s not a source of serious concern that I would be hyper-anxious about.”

But in a small number of cases, strep A can turn dangerous when it invades parts of the body where bacteria don’t normally exist. When it goes into such areas, including the blood, cerebrospinal fluid, bone marrow and organs such as the brain and heart, it can spread quickly and kill.

The first reports of unusual activity as a result of invasive strep A, mostly involving children 5 and under, came from the Netherlands between March and July. It was not only the number of cases and their severity, doctors said in a preprint research paper posted Dec. 13, but also the fact that many of the patients had been co-infected with viruses such as the flu or chickenpox. (Unlike in the United States, vaccinations for varicella, which cause chickenpox, are not a part of the children’s immunization program in the Netherlands.)

In 2018 and 2019, most of the kids seen at Dutch hospitals with invasive strep A developed sepsis, a systemic infection or pneumonia. But this year, many were diagnosed as suffering from necrotizing fasciitis, a flesh-eating disease that involves bacteria that destroys tissue under the skin. Physicians Evelien B. van Kempen, Patricia C.J. Bruijning-Verhagen, and their co-authors urged the public to be aware that early recognition and prompt treatment may save lives.

“Clinicians and parents should be vigilant and aware of unusual pediatric presentations,” they wrote.

Serious illness in children has also been reported in the United Kingdom, Netherlands, France, Ireland and Sweden, but the patterns aren’t always the same. In the U.K., doctors reported a surge in scarlet fever — which is also caused by strep A bacteria — at around the same time as the invasive cases. But that wasn’t seen in the Netherlands.

Several hospitals in the United States said they are unaware of unusual scarlet fever activity in their areas.

Figuring out what’s going on in the United States is trickier than in some other countries because of the lack of a national heath-care system that facilitates tracking of cases. CDC spokeswoman Kate Grusich said in an email that it is too soon to say whether case numbers “are just returning to pre-pandemic levels, or if they are rising beyond what we would normally expect.”

The “CDC is watching these data closely, and talking with surveillance sites and hospitals in multiple states to learn more about any trends,” she said.

The email listservs for pediatricians and infectious-disease specialists in this country started blowing up in October with a question from a doctor in the Midwest: Was anyone else seeing an increase in invasive strep A?

The responses were mixed, as expected, given that such cases tend to cluster. Boston Children’s had not seen anything concerning. But physicians in Kansas City, Houston and Denver had.

At Texas Children’s, Versalovic said some children have come in with low blood pressure and septic shock, some with bacterial pneumonia, and still others with skin infections. Several were so ill that they required intensive care. He worries some of the cases are being missed. To diagnose invasive strep A, doctors must take samples of a patient’s blood, skin, or fluid in the lungs or other areas. But if a child needs emergency care, there may not be time to consider the cause of the illness.

Invasive strep A “does not follow a simple linear progression,” he said.

In Denver, Samuel Dominguez, an infectious-disease specialist at Children’s Hospital Colorado and a professor at the University of Colorado School of Medicine, said the cases he had seen were “across the age spectrum” in children, noting that they may be more susceptible because bacteria tend to colonize more aggressively in their throats and skin than in adults.

Dominguez sought to balance reassurances that this is a relatively rare infection with calls to be on the lookout for warning signs.

Versalovic agreed. “We don’t want to raise too many alarms, but these infections can progress very rapidly,” he said.

Myers said all the patients seen at Children’s Mercy in Missouri have recovered with treatment, but she urged parents to make sure their children’s vaccinations are up to date to prevent a viral infection that may open the doors to a more severe bacterial one. “I think there are a lot of things at play we don’t fully know yet,” she said.

One of the tricky things about the illness is that it can look so different in different children, she said. The child having trouble moving their eyeball had an infection of the soft tissues of the eye socket; the one with the lump behind the ear, an infection of the bone in that area; and the third patient, a collection of pus in the back of the throat.

Myers urged parents to err on the side of caution.

“If a child looks sicker than they should be after they develop a fever, it’s always a good idea to bring them to a doctor if they have trouble breathing, or you notice something else — even a swollen eye,” she said.