Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.

No abstract

Objective: To evaluate the efficacy of ivermectin (IVM) as an addition to the standard of care (SOC) treatment in COVID-19 patients with mild and moderate disease Materials and Methods: A randomized clinical trial (Trial registration # NCT04392713) was carried out at Combined Military Hospital Lahore from March 15, 2020, to June 15, 2020. Eighty-six patients with reverse transcriptase-polymerase chain reaction (RT-PCR) proven SARS-CoV-2 infection completed the trial protocol. Patients were stratified via the lottery method into two groups. Group A was administered standard of care (SOC) treatment as per existing hospital guidelines whereas group B was given ivermectin (single dose of 12 milligrams) along with SOC treatment. PCR was repeated at 72 hours, 7th day, and at 14th day of admission for both the groups and the point at which the PCR became negative was noted. Complete blood counts, liver function tests and renal function tests were done at recruitment, 7th day, and 14th day. The primary outcome was the viral clearance, measured as days to achieve PCR negativity. The secondary outcome was the development of any adverse side effects pertinent to ivermectin or derangement in baseline laboratory parameters. Results: In group A, 36 (80%) participants were males, and 9 (20%) were females, whereas in group B, 37 (90.2%) were males and 4 (9.8%) were females. Mean age was 39.0 +/- 12.6 and 42.2 +/- 12.0 years for groups A and B, respectively (p= 0.394). There was early viral clearance in group B as compared to group A (p=0.001). No adverse reaction or derangements in laboratory parameters was noted in the intervention arm during the trial period. Conclusion: In the intervention arm, early viral clearance was observed and no side effects were documented. Therefore ivermectin is a potential addition to the standard care of treatment in COVID-19 patients.

No abstract

Background & Aims: High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored. Methods: In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age-and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up. Results: Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels. Conclusions: Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.