A Unique Triad of Invasive Sinusitis, Brain Abscess with Focal Cerebritis, and COVID-19.

BACKGROUND We present a case of invasive sinusitis with rhinocerebral infection in a patient who had mild symptoms of COVID-19 infection and did not receive any immunosuppressive therapies. CASE REPORT A 49-year-old man with a history of uncontrolled diabetes presented to the hospital with multiple generalized tonic clonic seizures. He had recently been diagnosed with mild COVID-19 and was treated at home with supportive care only. He was found to have cerebritis in the right frontal lobe along with right fronto-ethmoid sinusitis. He underwent extensive testing with nasal endoscopy with gram stain and culture, cryptococcal studies, 1-3-Beta-D glucan, blood cultures, fungal CSF studies, Lyme disease, HIV, Fungitell assay, and galactomannan studies, which were all negative. He was started on i.v. antibacterial therapy with cefepime, vancomycin, and metronidazole along with amphotericin B. After 2 weeks, his repeat imaging revealed progression of cerebritis along with new early abscess. Given these findings, his antibiotics were changed to meropenem and the amphotericin B dose was increased. He was recommended debridement and sinus surgery but refused. During the course of treatment, he developed acute kidney injury and was switched to Posaconazole. Unfortunately, the patient decided to leave against medical advice 6 weeks into admission. He was advised to continue Posaconazole and levofloxacin but he could only afford levofloxacin. He was then recommended long-term levofloxacin. He has since recovered, with resolution of cerebritis noted in follow-up imaging 1 year later. CONCLUSIONS Our patient had mild COVID-19 infection and presented with secondary infective complications, which are usually associated with an immunocompromised state, despite receiving no immunosuppressives. It is imperative that all clinicians treating COVID-19 be watchful for fungal or bacterial co-infections in patients with active SARS-CoV-2 infection, even if the presenting symptoms are mild, particularly if other risk factors are present.

Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD.

BACKGROUND: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents. RESULTS: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response. CONCLUSIONS: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.