Multimodality treatment in immunocompromised patients with severe COVID-19: the role of IL-6 inhibitor, intravenous immunoglobulin, and haemoperfusion.

Cytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID-19). Multiple anti-inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life-threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID-19-related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO2:FiO2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID-19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

BACKGROUND: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. METHODS: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-ß-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. RESULTS: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. CONCLUSIONS: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.