The offices of MEC Sindiswa Gomba and superintendent-general Dr Thobile Mbengashe are in the same building as the provincial call centre.
The MEC and SG have both tested negative.
Health department spokesperson Sizwe Kupela said the department would be working with Buffalo City Metro's environmental health services in temporarily closing the affected section for decontamination and deep cleaning.
“For now, the call centre and the offices of the senior officials will remain open,” said Kupelo. “All contacts of the positive employees will be followed up with for tracing and testing. This will also apply to all other staff in the building.”
Kupelo said the four officials tested positive despite all precautions taken, including the use of personal protective equipment and hand sanitisers.