The Dow Jones Industrial Average sank 344.93 points, or 1.16 percent, to end at 29,438.42. The S&P 500 was down 41.74 points, or 1.16 percent, to 3,567.79. The Nasdaq Composite Index decreased 97.74 points, or 0.82 percent, to 11,801.60.
All the 11 primary S&P 500 sectors pulled back, with energy closing down 2.88 percent, leading the losses.
U.S.-listed Chinese companies traded mostly lower, with eight of the top 10 stocks by weight in the S&P U.S. Listed China 50 index ending the day on a downbeat note.
The negative market moves came as new coronavirus cases continued to spiral in the United States.
New York City officials said Wednesday its public school system would close in a bid to contain rising COVID-19 cases.
The United States has reported more than 11.4 million cases in total with over 250,000 deaths as of Wednesday afternoon, showed a tally by Johns Hopkins University.
Investors also closely followed news on potential vaccines.
U.S. drugmaker Pfizer and its German partner BioNTech said Wednesday that a final analysis of clinical-trial data showed their COVID-19 vaccine candidate was 95 percent effective, adding they plan to submit an application for emergency use authorization "within days."
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