Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). METHODS: We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. RESULTS: Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. CONCLUSION: Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

POS-497 SUCCESSFUL BARIATRIC SURGERY FOLLOWING SECOND RENAL TRANSPLNATATION. AND OTHER COMPLICATIONS DURING THE JOURNEY

Introduction: Obesity is highly prevalent among patients with renal transplants. It is associated with increased risk of overall mortality, obesity-related complications such as diabetes, increased renal graft loss rates and shortened graft survival. Roux en Y gastric bypass in contrast to other non malabsorptive procedures, may affect the pharmacokinetics of certain drugs, which is of particular importance for immunosuppressant drugs required by patients post-transplant to avoid graft rejection. Methods: 43-year-old female known case of IgA nephropathy biopsy proven in 2000, progressed to end stage renal disease (ESRD) and was initiated on hemodialysis. She underwent live unrelated renal transplantation. Creatinine was 79 micromole/L and eGFR 85ml/min/1.73 m2. Her maintenance immunosuppression included azathioprine 50 mg daily, cyclosporine 75 mg bid and prednisolone 5 mg daily. She had two successful pregnancies post renal transplantations. She developed post renal transplant diabetes in 2013 and uncontrolled hypertension. She had persistent microscopic hematuria. Her creatinine peaked up to 275 micromol/L, her allograft kidney biopsy showed histopathologic features for mild acute T-cell mediated rejection (probably modified slightly by anti-rejection treatment). Grade 1A by Banff working grading. C4d stain is negative with background of focal proliferative and sclerosing glomerulonephritis with associated IgA deposits, consistent with IgA nephropathy ("M1, E1, S1, T0" Oxford classification). Her rejection was treated with pulse IV steroids, azathioprine was changed to mycophenolate and dose of cyclosporine was increased to 100 mg bid. Her creatinine came down to 105 micromol/L. Her post transplantation course involved purpuric rash, joint pain, abdominal pain, h/o HSP biopsy proven with elevated ESR and CRP most likely this is HSP again associated with medication exposure, possible the fibrate. Results: She lost follow up in our clinic and showed up after 5 years with uremic symptoms and creatinine of 1,063micromol/L and was initiated on hemodialysis in 2019. She had second live unrelated renal transplantation, she received 3 sessions of plasma exchange and IVIG prior to transplantation and was maintained on tacrolimus, mycophenolate and prednisolone. Her creatinine was 88 micromol/L. She had Laparoscopic sleeve gastrectomy and Dermo lipectomy of abdominal wall 2 months following her transplantation and lost 22 kgs since then, her BMI was 32 kg/m2 dropped to 24 kg/m2 in 6 months duration. The patient suffered from recurrent multi drug resistant E.Coli urinary tract infection treated with IV ertapenem and continued on trimethoprim sulpha- methoxazole prophylaxis for 6 months. She is still using insulin in smaller doses and her blood sugar is within acceptable ranges. She recently suffered from covid 19 pneumonia requiring home quarantine during which her creatinine went up to 106 micromol/L but settled down to baseline of 88 micromol/L during further follow up. Conclusions: Limited evidence suggests that bariatric surgery is safe and feasible for selected obese patients post-renal transplant. It is associated with good, if variable, short-term excess weight loss and resolution of co-morbidities. More studies should address long term complications in renal trnasplant patient population. No conflict of interest