Four months after the first Minnesotan died of COVID-19, health officials still aren't sure how lethal the pandemic is to people in the state.

The math is simple when dividing 1,574 deaths by 51,153 known cases in Minnesota to reach a 3.1% death rate, which is close to the 3.4% rate in China when COVID-19 emerged this winter. Known cases represent a fraction of infections, though, making the overall death rate lower and more complicated.

"I don't think we're going to be able to answer that question for a while," said Dr. Timothy Schacker, vice dean for research at the University of Minnesota Medical School.

Total case numbers include three deaths and 871 confirmed infections reported Sunday by the Minnesota Department of Health, along with 273 COVID-19 patients in hospitals and 115 of them in intensive care.

The trouble from the start in calculating the mortality risk has been the lack of a reliable denominator: the actual number of people infected by the SARS-CoV-2 coronavirus. Federal estimates suggest that one known COVID-19 case represents 10 unknown infections, meaning the virus could have already spread in Minnesota to a half-million people — many of whom never had symptoms or sought testing.

If true, then Minnesota's death rate from infection would be closer to 0.31%.

A shortage of testing supplies early in the pandemic made it hard to assess the death risk, said Dr. Matthew Prekker, a pulmonary and critical care specialist for Hennepin Healthcare. "Because of testing rolling out slowly, people were isolating, quarantining and not coming in always. So we don't really know what the denominator is and I think it will be some time before we understand that."

Even 1% rate is significant

The U.S. Centers for Disease Control and Prevention has reviewed available evidence and estimated a mortality rate of 0.65% — ranging between 0.5% and 0.8% depending on the rate of people with asymptomatic cases and how infectious they are to others.

Even a death rate below 1% is significant, as the rate for seasonal influenza is about 0.1%.

"One chance in 1,000 still gets your attention, you know?" said Dr. Frank Rhame, a virologist with Allina Health in Minneapolis. "One in 1,000 starts to be where I would change the way I go about things."

Risk varies by age and with underlying health conditions such as diabetes and heart disease. People 70 or older have suffered 10% of the known COVID-19 cases in Minnesota but 80% of the deaths.

Rhame said the death risk is "20% for people above 80 years of age, and less than a tenth of a percent for people in their 20s who are otherwise healthy, and it varies as a continuum in between."

The initial high death rate out of China was unlikely to hold up due to a grim phenomenon known as the "harvesting effect," by which the emergence of an epidemic or even a heat wave causes a surge in fatalities among the most vulnerable who are at imminent risk of death already, said Ali Mokdad, a population health researcher at the University of Washington's Institute for Health Metrics and Evaluation, or IHME.

COVID-19's death rate will always be a moving target, he said. "It's not 3.4%. It's not 0.6."

IHME's models on COVID-19 deaths have been sensitive to these changes, adjusting predictions based on how deaths in the most recent weeks have adjusted cumulative growth.

An IHME update last week lowered the estimated national toll, accounting for increased mask-wearing and its ability to reduce viral transmission. IHME predicts 1,873 COVID-19 deaths in Minnesota by Nov. 1 — and estimates that 95% mask-wearing in the state could reduce that by 124.

Modeling is getting better at predicting deaths; now the public needs to react to what it tells them to do to reduce their risks, he said. "We need to move from predictability to adaptability."

Other viruses cause higher fatality rates. The global MERS outbreak also involves a coronavirus and has a case fatality rate as high as one-third. The virus doesn't spread easily from person to person, though, resulting in fewer than 3,000 cases and fewer than 800 deaths worldwide since 2012.

A low death rate is still frightening when paired with a virus such as SARS-CoV-2 with a high infection rate, said Michael Osterholm, executive director of the U's Center for Infectious Disease Research and Policy.

"Which is worse: a disease that kills 1 in 10 people but only 100 people in the population get it? Or a disease that kills one in a thousand people but 5 million people in the population get it?" he said. "That's what you're up against here."

While there is a static death rate from untreated SARS-CoV-2 infections, doctors said that isn't as relevant in the U.S. — where severe cases are treated and the quality of medical care is improving.

Doctors have learned more about when to place severe COVID-19 patients on ventilators, for example, and how to adjust settings over time to help them maintain lung function. The placement of patients facedown for long stretches while on ventilators has helped as well.

No known drug treatments existed at the start of the pandemic, but now doctors have a proven antiviral along with a steroid for hospitalized patients. Donor plasma from recovered COVID-19 patients holds promise as a therapy, too.

"What we have to offer today to people is completely different than what we had to offer to that very first patient who was in our ICU back in March," said the U's Schacker.

Death risks also vary regionally based on the diversity and chronic disease levels of populations. Regions with manageable case levels also can provide usual levels of monitoring and care to patients, whereas regions swarming with COVID-19 have to spread thin their medical resources.

Slowing the spread

The guiding premise of Gov. Tim Walz's response to the pandemic in Minnesota — from the 51-day state lockdown in the spring to the mask mandate that took effect Saturday — has been to slow the virus to keep the pressure off hospitals and prevent any deaths due to lack of medical resources.

Osterholm said many regions in the U.S. have fallen off the "case cliff" this summer when their medical resources are stretched to the point that death risks increase. Minnesota was briefly on that ledge in May, he added, when hospitals were unable to maintain a 1-to-1 ratio of specially trained critical care nurses to COVID-19 patients in ICUs.

"When you have that happen, that's when you start losing more patients," he said. "So much of this isn't about the virus itself. It's about how we treat it, how we are able to respond."

Health officials warn that those in a low-risk category for COVID-19 mortality still need to heed the risks of morbidity and lingering complications.

Hennepin Healthcare contributed findings from 150 patients to a national study looking at recovery rates after COVID-19 symptoms emerged. Published by the CDC on Friday, the study showed that 35% of patients who received only outpatient treatment had not returned to usual health two to three weeks after they were diagnosed. Among patients ages 18 to 34, about one-fifth still reported problems.

The trend has been noticeable in former COVID-19 patients coming back to the emergency room, said Prekker, a principal investigator of the research effort at Hennepin Healthcare.

"They're just not better so they're coming back asking for help with things like persistent muscle aches, fatigue, just no energy," Prekker said, "and there are people who still have respiratory symptoms that linger afterward. Persistent cough is a big thing I've seen. Folks are concerned about going back to work when they're still coughing."

Jeremy Olson • 612-673-7744