A lthough most coronavirus disease 2019 (COVID-19) infections are self-limited, some develop into sepsis and multisystem organ failure (MSOF), 1 resembling lipotoxic acute pancreatitis. 2,3 Understanding underlying mechanisms may guide supportive care while clinical trials are ongoing. Unsaturated fatty acids (UFAs) generated by adipose lipolysis 2,3 cause MSOF, including acute lung injury. 2 Severe acute pancreatitis and severe COVID-19 share obesity as a risk factor, 4 along with lipase elevation, 5 hypoalbuminemia, 1 and hypocalcemia. 6 The latter 2 may progress undetected because calcium-albumin correction calculations (eg, https:// www.mdcalc.com/calcium-correction-hypoalbuminemia) can pseudonormalize calcium values (eg, uncorrected calcium of 5.9 mg/dL and albumin of 0.1 g/dL to corrected calcium of 9.0 mg/dL). Notably, calcium ameliorates MSOF, 7 and UFAs cause nonendocrine hypocalcemia. 7 The ACE2 receptor resides on adipocytes 8 containing triglycerides and adipocyte triglyceride lipase (ATGL) and on pancreatic acini expressing pancreatic triglyceride lipase (PNLIP). 2 Both oleic acid (C18:1) administration and adipose lipolysis 3 by PNLIP can cause acute lung injury and MSOF. These, and previous data showing that UFAs depolarize mitochondria, 2 inhibit complexes I and V, 3 decrease adenosine triphosphate, release intracellular calcium, 3 and increase inflammatory mediators, 3 made us explore lipotoxicity during severe COVID-19. This approach, culminating in clinical advice to keep calcium and albumin levels normal from early on in the disease, is summarized in Figure 1A and explained diagrammatically in supplementary figure 1. Methods See Supplementary Materials. Results Hypocalcemia and Hypoalbuminemia Occur Early During Severe Coronavirus Disease 2019 Seven of 15 hospitalized patients were discharged home by 3. 4 ±1.6 days. One died of hypoxemic failure after *Authors share co-first authorship.

Obesity sometimes seems protective in disease. This obesity paradox is predominantly described in reports from the Western Hemisphere during acute illnesses. Since adipose triglyceride composition corresponds to long-term dietary patterns, we performed a meta-analysis modeling the effect of obesity on severity of acute pancreatitis, in the context of dietary patterns of the countries from which the studies originated. Increased severity was noted in leaner populations with a higher proportion of unsaturated fat intake. In mice, greater hydrolysis of unsaturated visceral triglyceride caused worse organ failure during pancreatitis, even when the mice were leaner than those having saturated triglyceride. Saturation interfered with triglyceride’s interaction and lipolysis by pancreatic triglyceride lipase, which mediates organ failure. Unsaturation increased fatty acid monomers in vivo and aqueous media, resulting in greater lipotoxic cellular responses and organ failure. Therefore, visceral triglyceride saturation reduces the ensuing lipotoxicity despite higher adiposity, thus explaining the obesity paradox.

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Intervertebral disk (IVD) degeneration is a multifactor process that results in the physical destruction of the nucleus pulposus (NP) and annulus fibrosus (AF). This compromises IVD function and causes significant disability and economic burden. Strategies to replace the entire composite structure of the IVD are limited and most approaches do not recapitulate the heterogenous biochemical composition, microarchitecture or mechanical properties of the native tissue. Our central hypothesis was that donor IVDs which resemble the size and biochemistry of human lumbar IVDs could be successfully decellularized while retaining the tissue's structure and function with the long-term goal of creating a composite scaffold for tissue engineering the human IVD. Accordingly, we optimized a procedure to decellularize bovine tail IVDs using a combination of detergents, ultrasonication, freeze-thaw cycles, and nucleases. The resultant decellularized whole IVD xenografts retained distinct AF and NP regions which contained no visible intact cell nuclei and minimal residual bovine deoxyribose nucleic acid (DNA; 65.98 ± 4.07 and 47.12 ± 13.22 ng/mg, respectively). Moreover, the NP region of decellularized IVDs contained 313.40 ± 50.67 µg/mg glycosaminoglycan. The presence of collagen type II was confirmed via immunohistochemistry. Additionally, histological analysis of the AF region of decellularized IVDs demonstrated retention of the native angle-ply collagen microarchitecture. Unconfined compression testing demonstrated no significant differences in swelling pressure and toe-region modulus between fresh and decellularized IVDs. However, linear region moduli, peak stress and equilibrium moduli were all significantly reduced. Together, this research demonstrates a successful initial step in developing a biomimetic acellular whole IVD xenograft scaffold for use in IVD tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2412-2423, 2018.

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