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Roxanne Khamsi: The mysterious aftermath of infections

‘Long COVID’ is just the latest example of a pathogen causing surprising persistent effects.

(Tyler Comrie | The New York Times) The Mysterious Aftermath of Infections

In 2000, the small farming town of Walkerton, Ontario, suddenly became known to scientists around the world.

During the second week of May that year, the town, about 115 miles northwest of Toronto, got more than five inches of rain. Bacteria from manure on a farm was carried by runoff to a nearby well. Public utilities operators failed to appropriately monitor the water supply or to quickly advise the town how to ward off contamination, a government inquiry later concluded.

Without that information, Walkerton residents continued to drink the water, and more than 2,300 people became sick. Twenty-four children experienced severe kidney damage that occurred after the gastrointestinal symptoms subsided. Seven people died.

The culprits turned out to be a particularly dangerous strain of E. coli and Campylobacter jejuni bacteria, both known to cause stomach cramps and diarrhea. Yet even after the source of the outbreak was identified, the health disaster did not end.

In the years that followed, doctors saw more people in the town suffering from problems such as chronic fatigue, neurological damage and arthritis. A study of the children in Walkerton treated for kidney damage conducted five years later found that a few had slightly elevated protein levels in their urine, suggesting that their kidneys had not fully recovered.

The Walkerton outbreak was an early and substantive step forward as researchers build our understanding that pathogens can cause harm well beyond their initial attack.

Now, with the coronavirus pandemic, we are seeing more proof that an infection can cause lasting damage. What scientists want to understand is, with the coronavirus and other pathogens, when do the infections end and longer-term illnesses begin? There’s a tremendous amount of mystery.

Solving that mystery will help scientists better understand the wide-ranging complications from Covid-19, including the lingering effects known as “long Covid.” Studies have found that even some people with mild Covid-19 developed lung damage, for example. Autopsies have detected the coronavirus in heart tissue, and there is concern about lasting cardiovascular damage in survivors. Long Covid, which recently received the scientific name “post-acute sequelae of SARS-CoV-2 infection,” may have links to problems including severe fatigue and memory lapses.

Scientists have linked many infections to seemingly disparate ailments that crop up later. They’ve known for many years that an untreated case of strep throat, caused by streptococcal bacteria, can lead to a type of heart disease. More examples have piled up through the decades: Lyme disease can cause a form of arthritis. The bacterium Helicobacter pylori can produce ulcers and stomach cancer. Some strains of human papillomavirus can cause cervical, anal and throat cancer.

Medicine has begun only to scratch the surface of how infectious diseases can cause damage far beyond the initial symptoms. One well-established complication of a bacterial or viral infection is Guillain-Barré syndrome, an immune reaction against the body’s nervous system that can cause weakness and, in some cases, paralysis. Most people recover fully, but by some estimates it is fatal in around one in 20 cases.

One potential explanation for Guillain-Barré syndrome — which could apply to other complications — might have to do with a phenomenon called “molecular mimicry,” said Dr. Prathit Kulkarni, an infectious diseases specialist at the Baylor College of Medicine. If the pathogen’s proteins are similar in shape to those found in the human body, antibodies might accidentally react against a person’s own organs, Dr. Kulkarni explains.

In addition to turning the body’s immune system against itself, a microbe can cause direct and irreparable tissue injury or ignite damaging inflammation, which could account for later illness and persistent symptoms.

Parsing these connections is tricky, in no small part because a virus or bacterium may no longer be in the body even though its reverberations linger. “By the time you’re caring for the person, the pathogen is long gone, it’s just that it’s initiated this cascade of immune-mediated damage,” said Dr. David Fisman of the University of Toronto’s Dalla Lana School of Public Health.

In the case of Covid-19, researchers have many different theories about what might cause lingering illness. One idea is that the coronavirus itself directly damages tissues by killing cells, and affected organs never recover. Another idea is that the virus prompts inflammation that indirectly causes harm to organs. Some researchers suggest that long Covid sufferers might harbor a reservoir of the coronavirus. They have speculated that the Covid-19 vaccine might spur an immune response that eliminates these reservoirs, which might explain why some people with long Covid report feeling better after vaccination.

Addressing the gaps in understanding complications that arise from infectious diseases will take time and dedication. For starters, the medical community needs to establish a clearer consensus on what these complications are for specific infectious diseases, according to Dr. Anneli Lauhio, a specialist in infectious diseases in Finland who has studied the morbidity caused by these illnesses. Doing so through large-scale studies, she said, “will change medicine a lot,” and help doctors identify these complications earlier and treat them.

We are starting to see strides in this direction. The U.S. National Institutes of Health has allocated $1.15 billion in funding for research into the prolonged health consequences of SARS-CoV-2 infection. Part of this effort will include large studies involving electronic health records, to capture a broad amount of data over time. Similarly, researchers in England and Australia created a global registry that will collect information about cases of newly diagnosed diabetes following Covid-19; some have suggested the infection elevates diabetes risk.

There are examples of promising studies to uncover the hidden repercussions of infection beyond Covid-19, too. Dr. Shannon Majowicz, a University of Waterloo epidemiologist and her collaborators have set up a new study to analyze 10 years of past data from medical databases to estimate the health burden — including possible long-term autoimmune or chronic inflammatory complications — of 14 infections commonly transmitted by food in British Columbia.

Scientists are better equipped nowadays to study post-acute complications of infectious diseases. Rapid genetic sequencing to find previously hard-to-detect viruses and bacteria is more readily available, and electronic health records make it easier to track people. With tools like these, it becomes possible to see the actual toll of infectious diseases beyond their acute symptoms. This information can help doctors better anticipate and treat complications.

Last May, because of the pandemic, the town of Walkerton had to cancel plans to commemorate the 2000 E. coli outbreak and its victims. All of the medical aftershocks of the water contamination two decades ago are still not understood. As with the current pandemic, the scientific work needed to understand the repercussions of infections continues even after an outbreak is declared “over.”

Roxanne Khamsi is a science journalist covering COVID-19.

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