High seroprevalence against SARS-CoV-2 in non-vaccinated patients with inflammatory bowel disease from Northern India.

BACKGROUND: The information on seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients with inflammatory bowel disease (IBD) and its comparison to healthy controls is sparse. We compared the seroprevalence rates in patients with IBD and healthy controls (HCs). METHODS: Patients with IBD and HCs (contact of patients) underwent SARS-CoV-2 antibody testing (chemiluminescent immunoassay: Siemens kit IgG against antigen-S1RBD) between July 2020 and April 2021. Information on demography, disease characteristics, drug history and past history of SARS-CoV-2 infection were noted. Patients on 5-aminosalicylic acid or no treatment were considered not on immunosuppressants and those who had received steroids, thiopurines or methotrexate within six months of inclusion were considered being on immunosuppressants. RESULTS: A total of 235 patients (51.9%, males; mean age, 38.7 ± 12.4 years; median disease duration, 60 months [interquartile range, IQR: 36-120]) (ulcerative colitis [UC]: 69.4%, Crohn's disease [CD]: 28.9%, IBD unclassified [IBDU]: 1.7%) and 73 HCs (mean age, 39.6 ± 10.9 years, 80% males) were enrolled. Of the 235 patients, 128 (54.5%) patients were on immunosuppressants and 107 (45.5%) were not on immunosuppressants. Seventy-four (31.5%) patients were seropositive, of which two (0.9%) had previous history of SARS-CoV-2 infection and none received coronavirus disease-19 (COVID-19) vaccine. Seroprevalence between IBD patients and HCs (32% vs. 27%, p > 0.05) and between patients with and without immunosuppressants (28.1% vs. 36%, p > 0.05) was similar. Age, gender, disease type, duration and activity in the last six months; and medication use were similar between patients with positive and negative serology. There was a progressive increase in seroprevalence from July 2020 to April 2021. CONCLUSION: Up to 1/3rd of patients with IBD were seropositive for immunoglobulin G (IgG) SARS-Cov-2 antibody indicating high seroprevalence in patients with IBD from Northern India.

Hybridization Approach Toward Novel Antituberculars: Design, Synthesis, and Biological Evaluation of Compounds Combining Pyrazinamide and 4-Aminosalicylic Acid.

Apart from the SARS-CoV-2 virus, tuberculosis remains the leading cause of death from a single infectious agent according to the World Health Organization. As part of our long-term research, we prepared a series of hybrid compounds combining pyrazinamide, a first-line antitubercular agent, and 4-aminosalicylic acid (PAS), a second-line agent. Compound 11 was found to be the most potent, with a broad spectrum of antimycobacterial activity and selectivity toward mycobacterial strains over other pathogens. It also retained its in vitro activity against multiple-drug-resistant mycobacterial strains. Several structural modifications were attempted to improve the in vitro antimycobacterial activity. The δ-lactone form of compound 11 (11') had more potent in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Compound 11 was advanced for in vivo studies, where it was proved to be nontoxic in Galleria mellonella and zebrafish models, and it reduced the number of colony-forming units in spleens in the murine model of tuberculosis. Biochemical studies showed that compound 11 targets mycobacterial dihydrofolate reductases (DHFR). An in silico docking study combined with molecular dynamics identified a viable binding mode of compound 11 in mycobacterial DHFR. The lactone 11' opens in human plasma to its parent compound 11 (t1/2 = 21.4 min). Compound 11 was metabolized by human liver fraction by slow hydrolysis of the amidic bond (t1/2 = 187 min) to yield PAS and its starting 6-chloropyrazinoic acid. The long t1/2 of compound 11 overcomes the main drawback of PAS (short t1/2 necessitating frequent administration of high doses of PAS).

Highlights from this issue

This is an important topic and an interesting paper to work through. Serum ammonia is important for the diagnosis and management of urea cycle disorders and acute liver failure. Based on the premise that serum ammonia levels are unreliable for the diagnosis of hepatic encephalopathy (HE) and not associated with the severity of HE in individuals with cirrhosis Aby and colleagues looked at serum ammonia ordering in adult patients presenting to a large mid-western healthcare system – 20 338 tests (8536 patients) over 5 years. 53% of the cohort had chronic liver disease, 8 patients had a Urea Cycle Disorder, 69 patients had Acute Liver Failure and 148 were on Sodium Valproate. Of the 20 338 tests, 1138 (6.5%) were ordered for a definitive, appropriate indication, while the remainder were felt to have been ordered inappropriately. There was no change in the proportions over time. This data has significant financial implications with hence the title – serum ammonia use: unnecessary, frequent and costly with the need to educate clinicians regarding appropriate ammonia testing - in essence when to do and when not to do – we don’t, for example, want to miss a urea cycle disorder. There is an excellent accompanying commentary Testing for ammonia: do as I say, not as we do which includes a nice table on when to test in the hospital setting (See page 275).

Ulcerative Colitis: Rapid Evidence Review

Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.

Inflammatory Indexes for Assessing the Severity and Disease Progression of Ulcerative Colitis: A Single-Center Retrospective Study.

Background: Active and severe ulcerative colitis (UC) and non-response to 5-aminosalicylic acid (5-ASA) are related to poor outcomes and should be accurately identified. Several integrated inflammatory indexes are potentially useful to assess the disease severity in patients with acute or critical diseases but are underexplored in patients with UC. Methods: Patients with UC consecutively admitted to our hospital between January 2015 and December 2020 were retrospectively grouped according to the activity and severity of UC and response to 5-ASA. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), and C-reactive protein-to-lymphocyte ratio (CLR) were calculated. The areas under receiver operating characteristic curves (AUC) were calculated. Results: Overall, 187 patients with UC were included, of whom 151 were active, 55 were severe, and 14 were unresponsive to 5-ASA. The active UC group had significantly higher NLR, PLR, SII, and PAR levels. SII had the greatest predictive accuracy for active UC, followed by PLR, PAR, and NLR (AUC = 0.647, 0.641, 0.634, and 0.626). The severe UC group had significantly higher NLR, PLR, SII, PAR, CAR, and CLR levels. CLR had the greatest predictive accuracy for severe UC, followed by CAR, PLR, SII, NLR, and PAR (AUC = 0.732, 0.714, 0.693, 0.669, 0.646, and 0.63). The non-response to the 5-ASA group had significantly higher CAR and CLR levels. CAR had a greater predictive accuracy for non-response to 5-ASA than CLR (AUC = 0.781 and 0.759). Conclusion: SII, CLR, and CAR may be useful for assessing the severity and progression of UC, but remain not optimal.

Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System.

OBJECTIVE: Our aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD. DESIGN: This was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality. RESULTS: The analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p>0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01). CONCLUSION: VDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.