Tokyo, Shanghai, Hong Kong and Seoul were lower while Sydney advanced. U.S. futures declined, with the contracts for both the S&P 500 and the Dow industrials 0.1% lower.
Surging coronavirus cases in Asia have raised uncertainty about the pace of recovery from the pandemic.
The omicron coronavirus variant has swept across Australia and other countries in the region despite high vaccination rates and strict border policies. Japan reported more than 13,000 new infections on Wednesday, the highest level in four months. China, whose zero-COVID policies are being challenged by outbreaks just weeks ahead of the Beijing Winter Games, is testing and in some cases locking down entire cities.
Tokyo's Nikkei 225 index dropped 1% to 28,489.13, while the Shanghai Composite shed 1% to 3,560.59. In Seoul, the Kospi lost 0.4% to 2,962.09.
The Hang Seng in Hong Kong edged 0.1% lower, to 24,379.67 and the S&P/ASX 200 added 0.5% to 7,474.40. India's Sensex edged 0.1% higher.
Taiwan's benchmark rose 0.3% after TSMC, the world's largest contract manufacturer of computer chips, reported a record quarterly profit of just over $6 billion.
The yield on the 10-year Treasury was steady at 1.74%.
Apart from the direct impact from big coronavirus outbreaks on normal business activity, spill over effects on manufacturing and shipping could further hinder a rebound from the past two years of disruptions.
“So far, the market’s reaction to the omicron wave has been moderate, but it is worth paying attention to worries about further impacts to global supply chains which could trigger risk-off trade," Anderson Alves of ActivTtrades said in a report.
On Wednesday, the S&P 500 rose 0.3% to 4,726.35. The Dow Jones Industrial Average eked out a 0.1% gain, closing at 36,290.32. The Nasdaq composite rose 0.2% to 15,188.39. All are on pace for a weekly gain.
Smaller company stocks lost ground. The Russell 2000 index fell 0.8% to 2,176.06.
Investors were focused on a report from the Labor Department which showed consumer prices jumped 7% last month. That's the fastest year-over-year pace in the consumer price index in nearly four decades. The sharp increase, which was in line with economists' forecasts, came a day after Fed Chair Jerome Powell told Congress that the central bank stands ready to raise rates to fight inflation.
The modest gains were led by technology stocks, retailers and other companies that rely on direct consumer spending.
Smaller company stocks lost ground. The Russell 2000 index fell 17.95 points, or 0.8%, to 2,176.06.
Wall Street has been closely watching rising inflation to gauge the impact on businesses and consumers, as well as on the Fed's plan to trim its support for the economy and markets.
The central bank is reducing bond purchases that helped keep interest rates low throughout the virus pandemic.
The market now puts the chances of the Fed raising short-term rates by at least a quarter point in March at around 75%. A month ago, it was about 36%.
Wall Street will get another update on rising inflation on Thursday, when the Labor Department releases December results from an index based on U.S. wholesale prices. It shows how inflation is affecting costs for businesses.
Businesses in many industries have been passing higher costs off to consumers, but have been warning that they will still feel a financial impact because of higher prices and supply chain problems.
Wall Street will be closely watching the latest round of earnings to see how companies are dealing with inflation.
Delta Air Lines reports its results on Thursday. Citigroup, JPMorgan Chase and Wells Fargo report results on Friday.
In other trading, U.S. benchmark crude oil lost 17 cents to $82.47 per barrel in electronic trading on the New York Mercantile Exchange. It gained $1.42 to $82.64 per barrel on Wednesday.
Brent crude, the basis for pricing international oils, lost 18 cents to $84.49 per barrel.
The U.S. dollar was unchanged at 114.64 Japanese yen. The euro fell to $1.1441 from $1.1444.
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