On September 18, 2021, about 0750, a Cessna 404, N5409G, was substantially damaged when it was involved in an accident near Sheridan, Wyoming. The pilot was not injured. The airplane was operated as a Title 14 Code of Federal Regulations Part 135 scheduled cargo flight. The pilot stated that he loaded the airplane, along with help from ground handlers, and that there were no HAZMAT packages presented during loading. The total weight of cargo was 154 lbs, and it was loaded behind a net in the aft cargo area. He stated that the flight and landing approach were uneventful, and he recalled configuring the airplane for landing by extending the landing gear and flaps. He began the landing flare, but his next recollection was of being in the airplane at the right side of the runway surrounded by a cloud of dust. He did not have any recollection of how the airplane got there. Examination of the airplane revealed that it had departed runway 15 shortly after landing. The landing gear had collapsed, the nose structure was deformed, and the runway surface exhibited a set of gouges that matched the dimensions of the right wheel rim, and two sets of slash marks consistent with propeller strike. The pilot refused emergency medical treatment at the accident scene, and visited his personal physician three days later, complaining of back and neck pain following the accident. During that visit, his vital signs, including his pulse oximetry, were normal. The pilot recounted the accident circumstances to the physician and was concerned about why he couldn’t remember the events. The medical record stated, “He does not believe he lost consciousness but is unclear.” The physical examination was unremarkable. The physician obtained a chest X-ray, which showed patchy infiltrates, and the pilot tested positive for COVID-19 the following day. He had blood tests that were normal and a brain MRI on October 11, 2021, did not reveal any acute findings. The pilot had reported remote surgeries and seasonal allergies to the FAA at his last medical examination without any use of medications. According to personal medical records, in February 2021, he reported having gastroesophageal reflux disease and using omeprazole to treat it.