The university's Center for Systems Science and Engineering showed about 52,100 new cases, the most since Aug. 14. In seven out of the last 10 days, the national figure was under 40,000.
Before Tuesday, the seven-day average was about 36,000.
The university also reported a spike in deaths nationwide -- more than 1,400, which is the highest daily toll since Aug. 12.
Since the start of the pandemic, there have been 6.61 million cases in the United States and 196,100 deaths.
Wednesday, pharma company Eli Lilly said an antibody-based drug has been shown to reduce the rate of hospitalization for COVID-19 patients with mild or moderate symptoms.
Lilly announced the results of the BLAZE-1 clinical trial, in which the drug LY-CoV555 or a placebo was given to 450 patients in an outpatient setting.
"[The data] suggest that LY-CoV555 ... has a direct antiviral effect and may reduce COVID-related hospitalizations," Eli Lilly Chief Scientific Officer Dr. Daniel Skovronsky said in a statement. "The results reinforce our conviction that neutralizing antibodies can help in the fight."
Antibody-based drugs are considered potentially effective in fighting COVID-19 until a vaccine is completed.
In Maine, the state's top health official has linked seven deaths to an indoor wedding there last month.
Dr. Nirav Shah told reporters the deaths have been traced to an Aug. 7 reception at the Big Moose Inn Cabins and Campground in Millinocket.
Shah said none of the dead actually attended the wedding or reception, but they were tied to a secondary spread after the event. Six of the deaths occurred at a senior center in Madison.
Dozens of people attended the wedding, which has been linked to nearly 200 Maine cases -- including an outbreak at the York County Jail.