COVID-19 Patients with GI Manifestations May be Associated with Extensive Microthrombosis in the Small Intestine, a Study from 13 Autopsy Cases

ABSTRACT

Background: More than 20% of COVID-19 patients have gastrointestinal (GI) symptoms, among which diarrhea is the most commonly seen symptom. Studies have suggested that patients with severe disease are more likely to have abdominal manifestations. Recent studies have also implicated that coagulopathy and thromboembolic as the major pathophysiological event leading to higher mortality. Besides thrombus in larger vessels, microthrombi appears to occur systemically and plays an important role in multiple organ dysfunction. However, fewer studies have focused on microthrombosis in the GI system. Design: 13 bronchial SARS-CoV-2 PCR proven autopsy cases were included in the study. Small intestinal specimens were obtained, and processed to routine hematoxylin and eosin (H&E) and CD61 immunohistochemistry (IHC). Related clinical and laboratory data were collected from patient chats. H&E and IHC slides were reviewed by two GI pathologists to evaluate histopathology and microthrombi. The degree of microthrombosis was graded as no microthrombi, focal (1- 2 per 10x), scattered (3-5 per 10x), and diffuse (≥6 per 10x). Results: Out of 13 patients (11 males, 1 female, age range 22-89 years old), 6 had diarrhea as the initial GI symptom, while others (7 patients) did not report any GI manifestations. Sections from the small intestine showed no acute inflammation in all cases. CD61 positive microthrombi was seen in all small intestine specimens, mainly located in the microvasculature of mucosa, and occasionally submucosal tissue. Patients who had diarrhea, 4/6 (66.7%) showed diffuse (greater than 6 per 10x field) microthrombi in the small intestine. In contrast, patients without GI symptoms, only 2/7 (28.5%) had diffuse microthrombi. Data from lab tests showed the D-dimer appeared to be higher in patients with diarrhea (median, 4067, range from 867 to 10000 ng/ml) compared to patients without diarrhea (median, 2820, range from 298 to 10000 ng/ml). There was no significant difference between median levels of C-reactive protein, prothrombin time (PT) and partial thromboplastin time (aPTT) between patients with or without diarrhea. Conclusions: Our study highlights that microthrombi frequently occurs in the GI system as reported in other organs. COVID-19 patients with initial GI manifestations, may develop severe microthrombosis and progress to sever disease.