I was able to work on an file already opened by Excel by disabling the warnings:

my $Excel = Win32::OLE->GetActiveObject('Excel.Application')
    || Win32::OLE->new('Excel.Application', 'Quit');
$Excel->{DisplayAlerts}=0;
my $Book = $Excel->Workbooks->Open($excel_file);
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Hope it can help people reaching this page with the same problem.