Lipemic serum in patients with Coronavirus Disease 2019 (COVID‐19) undergoing treatment

Abstract

We read with interest the article by Morrison et al. on acute hypertriglyceridemia secondary to tocilizumab in patients with severe coronavirus disease . 1 One patient also had pancreatitis, a dreaded complication of hypertriglyceridemia.Both patients were already on lopinavir/ritonavir before tocilizumab (added day 9 and 13) was added. Propofol was briefly used.We recently had two out of 47 patients with moderate/severe COVID-19 who were treated with lopinavir/ritonavir and developed significant hypertriglyceridemia resulting in lipemic serum. The first patient (51-year-old man) with undiagnosed stage II chronic kidney disease (estimated glomerular filtration rate 61.12 mL/min) and no history of lipid disorder or diabetes mellitus was started on lopinavir/ritonavir (400 and 100 mg twice daily for 14 days) on the 10th day of admission. Blood serum became lipemic on the 10th day of treatment (Figure 1). Serum triglyceride levels ranged between 921.2 and 1071.7 mg/dL (normal range <150 mg/dL). His serum amylase was normal. He was started on bezafibrate and the lipemic serum settled. The second patient (45-year-old man) with hypertension, dyslipidemia and uncontrolled diabetes mellitus was started lopinavir/ritonavir monotherapy on the 4th day of admission. His blood was reported to be lipemic on the 11th day of treatment despite being on atorvastatin. Fortunately he completed treatment without any complications. Follow-up showed no recurrence of lipemic serum in both patients. The second patient had risk factors for hypertriglyceridemia.Lopinavir/ritonavir is known to be associated with lipid abnormality, 2,3 more so than tocilizumab. One study showed that at 12 weeks of treatment of lopinavir/ritonavir in patients with human immunodefieciency virus, small but significant increase from baseline in the fasting total cholesterol and triglyceride was observed. 2 Our patients developed lipemic serum within 2 weeks of treatment. In Morrison's cases, it is possible that the lopinavir/ ritonavir had contributed to or even caused the hypertriglyceridemia. Therefore it is important for clinicians to be aware and monitor for complications given that the COVID-19 pandemic will continue and these two medications continue to be used until better treatment options become available.

Evaluation of Hypertriglyceridemia in Critically Ill Patients With Coronavirus Disease 2019 Receiving Propofol

“…The exact mechanism of tocilizumab-induced hypertriglyceridemia is unknown, but it is hypothesized that tocilizumab may interfere with IL-6-mediated uptake of fatty acids from the serum into skeletal muscle ( 37 , 38 ). Another report of two cases highlighted elevated triglyceride levels possibly secondary to lopinavir/ritonavir ( 28 ). It is unknown if these patients received propofol, but the authors mention that the patients had additional risk factors for hypertriglyceridemia.…”

“…Additionally, propofol is effective for decreasing respiratory drive, allowing for lung protective ventilator strategies, such as the utilization of low tidal volumes, higher positive end-expiratory pressures, and prone positioning ( 1 , 20 ). While the metabolic derangements secondary to COVID-19 have yet to be fully described, various reports have been published demonstrating hypertriglyceridemia patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possibly secondary to various therapies ( 27 , 28 ).…”

Insufficient etiological workup of COVID-19-associated acute pancreatitis: A systematic review

“…Hypertriglyceridemia, another established etiological factor frequently neglected, can also occur as a consequence of therapy, as in the case described by Morrison et al [ 20 ]. Not only tocilizumab[ 35 ] but propofol and ritonavir could also have been responsible for the elevation of serum triglyceride levels in this case[ 36 ]. Hypertriglyceridemia-associated drug-induced AP was observed[ 37 , 38 ] in association with the following drugs being tested for COVID-19 according to our search on clinicaltrials.gov: lisinopril, asparaginase, estrogens, isotretinoin, steroids, propofol, and ruxolitinib.…”

Lopinavir-Ritonavir in treatment of COVID-19: A dynamic systematic benefit-risk assessment

“…Serious gastrointestinal adverse effects included in the key risks for this assessment include pancreatitis, which has been associated with the use of LPVr [19,23,24]; most patients who developed pancreatitis during treatment for HIV had a prior history of this condition. Treatment with LPVr has been associated with an increase in triglycerides in patients treated for HIV [19], and amongst patients treated for COVID-19 [25][26][27][28], which is likely to be another contributory factor in the development of pancreatitis.…”