{"id":3995,"date":"2022-03-25T14:56:19","date_gmt":"2022-03-25T14:56:19","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=3995"},"modified":"2022-03-25T14:56:19","modified_gmt":"2022-03-25T14:56:19","slug":"pancreatic-damage-in-covid%e2%80%9019-why-how","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=3995","title":{"rendered":"Pancreatic damage in COVID\u201019: Why? How?"},"content":{"rendered":"\n<p>Authors:  <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Bacaks%26%23x00131%3Bz%20F%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=34331821\">Ferhat Bacaks\u0131z<\/a>,<sup>&nbsp;1&nbsp;<\/sup><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Ebik%20B%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=34331821\">Berat Ebik<\/a>,<sup>&nbsp;1&nbsp;<\/sup><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Ekin%20N%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=34331821\">Naz\u0131m Ekin<\/a>,<sup>&nbsp;1&nbsp;<\/sup>and&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=K%26%23x00131%3Bl%26%23x00131%3Bc%20J%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=34331821\">Jihat K\u0131l\u0131c<\/a><sup>&nbsp;2<\/sup>  <\/p>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#\">Int J Clin Pract.<\/a>&nbsp;2021 Aug 6 : e14692.doi:&nbsp;<a rel=\"noreferrer noopener\" href=\"https:\/\/dx.doi.org\/10.1111%2Fijcp.14692\" target=\"_blank\">10.1111\/ijcp.14692<\/a>&nbsp;[Epub ahead of print] PMCID:&nbsp; PMC8420122PMID:&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34331821\">34331821<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-abs-0001title\">Abstract<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0001title\">Object<\/h3>\n\n\n\n<p id=\"__p1\">We aimed to evaluate the elevation of amylase and lipase enzymes in coronavirus disease 2019 (COVID\u201019) patients and their relationship with the severity of COVID\u201019.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0002title\">Method<\/h3>\n\n\n\n<p id=\"__p2\">In this study, 1378 patients with COVID\u201019 infection were included. Relation of elevated amylase and lipase levels and comorbidities with the severity of COVID\u201019 was analysed. The effects of haemodynamic parameters and organ failure on pancreatic enzymes and their relations with prognosis were statistically analysed.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0003title\">Results<\/h3>\n\n\n\n<p id=\"__p3\">The 1378 patients comprised of 700 (51.8%) men and 678 (%49.2) women. Of all patients, 687 (49.9%) had mild and 691 (50.1%) patients had severe COVID\u201019 infection. Amylase elevation at different levels occurred in 316 (%23) out of 1378 patients. In these patients, the amylase levels increased one to three times in 261 and three times in 55 patients. Pancreatitis was detected in only six (%1.89) of these patients according to the Atlanta criteria. According to univariate and multivariate analyses, elevated amylase levels were significantly associated with the severity of COVID\u201019 (odds ratio [OR]: 4.37;&nbsp;<em>P<\/em>&nbsp;&lt;&nbsp;.001). Moreover, diabetes mellitus (DM; OR: 1.82;&nbsp;<em>P<\/em>&nbsp;=&nbsp;.001), kidney failure (OR: 5.18;&nbsp;<em>P<\/em>&nbsp;&lt;&nbsp;.001), liver damage (OR: 6.63;&nbsp;<em>P<\/em>&nbsp;&lt;&nbsp;.001), hypotension (OR: 6.86;&nbsp;<em>P<\/em>&nbsp;&lt;&nbsp;.001) and sepsis (OR: 6.20;&nbsp;<em>P<\/em>&nbsp;=&nbsp;.008) were found to be associated with mortality from COVID\u201019.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0004title\">Conclusion<\/h3>\n\n\n\n<p id=\"__p4\">Elevated pancreatic enzyme levels in COVID\u201019 infections are related to the severity of COVID\u201019 infection and haemodynamic instability. In a similar way to other organs, the pancreas can be affected by severe COVID\u201019 infection.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0006title\">What\u2019s known<\/h3>\n\n\n\n<ul class=\"wp-block-list\" id=\"ijcp14692-list-0001\"><li>It has been suggested that COVID\u201019 can cause pancreatic damage.<\/li><li>There are a limited number of studies related to the possibility of an increase in the level of pancreatic enzymes in COVID\u201019 patients.<\/li><\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0007title\">What\u2019s new<\/h3>\n\n\n\n<ul class=\"wp-block-list\" id=\"ijcp14692-list-0002\"><li>COVID\u201019 does not directly cause pancreatic damage.<\/li><li>Pancreatic enzyme elevation in patients with COVID\u201019 develops in the advanced stages of the disease caused by multiple organ dysfunction and shock.<\/li><\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-sec-0008title\">1.\u2003INTRODUCTION<\/h2>\n\n\n\n<p id=\"__p15\">Coronavirus disease 2019 (COVID\u201019) infection was initially considered to attack only the upper respiratory tract, but was later found to potentially affect almost all systems. This is caused by the angiotensin\u2010converting enzyme 2 (ACE2) receptors that coronavirus binds to in order to enter the cells. These receptors are also commonly available in the gastrointestinal system such as in hepatic, pancreatic and colonic cells.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0001\">1<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0002\">2<\/a><\/p>\n\n\n\n<p id=\"__p16\">Recent studies have shown that COVID\u201019 infection can cause damage to the pancreas caused by the high expression of ACE2 receptors from the pancreatic tissue.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0003\">3<\/a>&nbsp;Additionally, it has also been reported that hyperglycaemia can occur because of pancreatic islet cell damage in patients with COVID\u201019 and that severe patients with COVID\u201019 should be followed up closely in terms of pancreatic damage.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0004\">4<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0005\">5<\/a><\/p>\n\n\n\n<p id=\"__p17\">In this study, we evaluated the amylase and lipase elevations in patients with COVID\u201019 in order to investigate the relationship between pancreatic enzyme elevations and the severity of COVID\u201019 infection and to identify the underlying conditions.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#\">Go to:<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-sec-0009title\">2.\u2003PATIENTS AND METHODS<\/h2>\n\n\n\n<p id=\"__p18\">The study included 1378 patients with COVID\u201019 infection who presented to our hospital between March and December 2020. Clinical characteristics including temperature, blood pressure, laboratory parameters, treatments and comorbidities were monitored throughout hospitalisation. In addition to other laboratory parameters, amylase and lipase levels were also studied in order to determine the ratio of patients with elevated pancreatic enzymes. Values above 105 U\/L for amylase and 65&nbsp;IU\/L for lipase were considered high.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0006\">6<\/a>&nbsp;Patients with pancreatitis were identified according to the Atlanta criteria.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0007\">7<\/a><\/p>\n\n\n\n<p id=\"__p19\">Additionally, pancreatic enzyme elevation in COVID\u201019 infection was investigated with regard to the severity of disease. Patients were divided into two groups based on the severity of their COVID\u201019 symptoms: mild (n&nbsp;=&nbsp;687) and severe (n&nbsp;=&nbsp;691). Patients with fever, headache, loss of taste and smell and generalised myalgia without tachypnoea (oxygen saturation &gt;92%) were considered to have a mild infection, whereas patients on invasive or non\u2010invasive respiratory support or with deteriorated haemodynamic conditions were considered to have severe COVID\u201019 infection.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0008\">8<\/a><\/p>\n\n\n\n<p id=\"__p20\">The causes of pancreatic enzyme elevation were compared between patients with mild and severe COVID\u201019 infection and between surviving and non\u2010surviving patients. Relation between elevated pancreatic enzymes and metabolic parameters, haemodynamic findings, single and multiple organ failures was also examined.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0009\">9<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0010\">10<\/a><\/p>\n\n\n\n<p id=\"__p21\">Hypotension was evaluated based on mean arterial pressure (MAP). A MAP value of 60\u2010110&nbsp;mmHg was accepted as normal, &lt;60&nbsp;mmHg as hypotensive and &gt;110&nbsp;mmHg as hypertensive.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0011\">11<\/a><\/p>\n\n\n\n<p id=\"__p22\">Liver damage was determined according to the 2019 European Association for the Study of the Liver (EASL) guidelines, based on the upper limits of normal (ULN) serum alanine aminotransferase activity (ALT) and serum alkaline phosphatase activity (ALP), as follows: ALT \u22655&nbsp;\u00d7&nbsp;ULN or ALP \u22652 ULN [in the absence of known bone pathology] or ALT \u22653 ULN with simultaneous increase of total bilirubin concentration \u22652 ULN.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0012\">12<\/a>&nbsp;Kidney injury was determined according to the RIFLE (Risk, Injury, Failure, Loss of kidney function and End\u2010stage kidney disease) criteria.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0013\">13<\/a><\/p>\n\n\n\n<p id=\"__p23\">The study was conducted in accordance with the Helsinki Declaration and the study protocol was approved by the local ethics committee (No: 611, Date: 16 October 2020).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ijcp14692-sec-0010title\">2.1. Statistical analysis<\/h3>\n\n\n\n<p id=\"__p24\">Data were analysed using SPSS 26.0 for Windows (Armonk, NY: IBM Corp.). Normal distribution of data was assessed using Kolmogorov\u2010Smirnov, Shapiro\u2010Wilk test, coefficient of variation, skewness and kurtosis. Continuous variables were expressed as mean and standard deviation (SD), and categorical variables were expressed as percentages (%). Student&nbsp;<em>t<\/em>&nbsp;test and Mann\u2010Whitney&nbsp;<em>U<\/em>\u2010test were used in paired groups to compare pancreatic enzymes and disorders of other organs between patients with severe and mild COVID\u201019 infection. ANOVA test was used for parameters homogeneously distributed in triple groups. Bonferroni correction was used to determine the significant results in groups. Welch&#8217;s ANOVA and Kruskal\u2010Wallis tests were performed for non\u2010homogeneous parameters. Pearson and Spearman correlation coefficients were used to analyse the relationship between pancreatic enzyme elevation and other parameters. Univariate and multivariate analyses were performed to determine the factors associated with pancreatic enzyme elevation. All tests were bilateral and a&nbsp;<em>P<\/em>\u2010value of &lt;.05 was considered significant.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#\">Go to:<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-sec-0011title\">3.\u2003RESULTS<\/h2>\n\n\n\n<p id=\"__p25\">The 1378 patients comprised of 700 (51.8%) men and 678 (%49.2) women. The prevalence of kidney failure, DM, ischaemic hepatitis and sepsis was significantly higher in patients with severe COVID\u201019 compared with patients with mild disease. Moreover, amylase and lipase levels were also higher in patients with severe COVID\u201019 (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0001\/\">1<\/a>).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">TABLE 1<\/h3>\n\n\n\n<p id=\"__p26\">Demographic data and biochemical parameters of patients with mild and severe COVID\u201019<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-regular\"><table><thead><tr><th><\/th><th>Mild COVID\u201019\u00b1SD<\/th><th>Severe COVID\u201019\u00b1SD<\/th><th><em>P<\/em><\/th><\/tr><\/thead><tbody><tr><td>N<\/td><td>687 (49.9%)<\/td><td>691 (50.1%)<\/td><td><\/td><\/tr><tr><td>Age<\/td><td>60.2 (29\u201084)<\/td><td>65 (51\u201086)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Gender F\/M<\/td><td>356\/331<\/td><td>322\/369<\/td><td>.053<\/td><\/tr><tr><td>Amylase (U\/L)<\/td><td>82.6&nbsp;\u00b1&nbsp;50.4<\/td><td>264.7&nbsp;\u00b1&nbsp;292.0<\/td><td>&lt;.001<\/td><\/tr><tr><td>Lipase (IU\/L)<\/td><td>59.7&nbsp;\u00b1&nbsp;51.2<\/td><td>79.0&nbsp;\u00b1&nbsp;24.2<\/td><td>.045<\/td><\/tr><tr><td>ALT (IU\/L)<\/td><td>70.4&nbsp;\u00b1&nbsp;60.2<\/td><td>82.7&nbsp;\u00b1&nbsp;56.4<\/td><td>&lt;.001<\/td><\/tr><tr><td>AST (IU\/L)<\/td><td>61.6&nbsp;\u00b1&nbsp;40.7<\/td><td>180&nbsp;\u00b1&nbsp;135.5<\/td><td>&lt;.001<\/td><\/tr><tr><td>ALP (IU\/L)<\/td><td>84.1&nbsp;\u00b1&nbsp;35.4<\/td><td>133.2&nbsp;\u00b1&nbsp;107.2<\/td><td>.295<\/td><\/tr><tr><td>GGT (IU\/L)<\/td><td>54.2&nbsp;\u00b1&nbsp;51.5<\/td><td>79.4&nbsp;\u00b1&nbsp;58.9<\/td><td>.099<\/td><\/tr><tr><td>T.Bil (mg\/dL)<\/td><td>0.67&nbsp;\u00b1&nbsp;0.33<\/td><td>1.95&nbsp;\u00b1&nbsp;1.53<\/td><td>&lt;.001<\/td><\/tr><tr><td>LDH (IU\/L)<\/td><td>411.9&nbsp;\u00b1&nbsp;210<\/td><td>1137&nbsp;\u00b1&nbsp;248.7<\/td><td>&lt;.001<\/td><\/tr><tr><td>Urea (mg\/dL)<\/td><td>45.7&nbsp;\u00b1&nbsp;26.9<\/td><td>187.0&nbsp;\u00b1&nbsp;92.8<\/td><td>&lt;.001<\/td><\/tr><tr><td>Creatinine (mg\/dL)<\/td><td>0.89&nbsp;\u00b1&nbsp;0.49<\/td><td>3.74&nbsp;\u00b1&nbsp;1.96<\/td><td>&lt;.001<\/td><\/tr><tr><td>Glucose (mg\/dL)<\/td><td>138&nbsp;\u00b1&nbsp;85.0<\/td><td>290&nbsp;\u00b1&nbsp;135<\/td><td>&lt;.001<\/td><\/tr><tr><td>WBC (cell\/\u00b5L)<\/td><td>9840&nbsp;\u00b1&nbsp;4485<\/td><td>18&nbsp;422&nbsp;\u00b1&nbsp;6039<\/td><td>&lt;.001<\/td><\/tr><tr><td>Lymphocyte (cell\/\u00b5L)<\/td><td>1993&nbsp;\u00b1&nbsp;665<\/td><td>1655&nbsp;\u00b1&nbsp;946<\/td><td>&lt;.001<\/td><\/tr><tr><td>CRP (mg\/L)<\/td><td>107.8&nbsp;\u00b1&nbsp;67.2<\/td><td>217.9&nbsp;\u00b1&nbsp;69.1<\/td><td>&lt;.001<\/td><\/tr><tr><td>Procalcitonin (ng\/mL)<\/td><td>1.04&nbsp;\u00b1&nbsp;4.65<\/td><td>8.03&nbsp;\u00b1&nbsp;19.7<\/td><td>&lt;.001<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0001\/?report=objectonly\">Open in a separate window<\/a><\/p>\n\n\n\n<p id=\"__p27\">Abbreviations: ALP, alkaline phosphatase, GGT, gamma glutamyl transpeptidase WBC, white blood cell, CRP, C reactive protein; ALT, alanine transaminase; AST, aspartate transaminase; LDH, lactate dehydrogenase; SD, standard deviation.<\/p>\n\n\n\n<p id=\"__p28\">Amylase elevation at different levels occurred in 316 (%23) out of 1378 patients. In these patients, the amylase levels increased one to three times in 261 and three times in 55 patients. Pancreatitis was detected in only six (%1.89) of these patients according to the Atlanta criteria. Amylase and lipase elevation was found to be related to the severity of COVID\u201019 infection in the remaining patients. The development of DM, kidney failure, hypotension and ischaemic hepatitis was found to be related to mortality from COVID\u201019 infection. However, there was no relationship between lymphopenia and elevated amylase levels (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0002\/\">2<\/a>). On the other hand, patients older than 65&nbsp;years were more likely to have (1.89 times) elevated increased enzyme levels.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">TABLE 2<\/h3>\n\n\n\n<p id=\"__p29\">Relationship between amylase level in COVID\u201019 patients and gender, comorbid status, severity and consequence of COVID\u201019, haemodynamic status, other organ failures and laboratory parameters<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-regular\"><table><thead><tr><th>Feature<\/th><th>Amylase (normal)<\/th><th>Amylase (1\u20103 times)<\/th><th>Amylase (more than 3 times)<\/th><th><em>P<\/em>\u2010values<\/th><\/tr><\/thead><tbody><tr><td>N\/%<\/td><td>1062 (77.0%)<\/td><td>261 (19.0%)<\/td><td>55 (4.0%)<\/td><td><\/td><\/tr><tr><td>Gender<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Female (678%\u201049.2%)<\/td><td>565 (83.3%)<\/td><td>100 (14.8%)<\/td><td>13 (1.9%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Male (700%\u201050.8%)<\/td><td>497 (71.0%)<\/td><td>161 (23.0%)<\/td><td>42 (6.0%)<\/td><td><\/td><\/tr><tr><td>COVID\u201019 severity<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Mild COVID\u201019 (687%\u201049.9%)<\/td><td>612 (89.1%)<\/td><td>71 (10.3%)<\/td><td>4 (0.6%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Severe COVID\u201019 (691%\u201050.1%)<\/td><td>450 (65.1%)<\/td><td>190 (27.5%)<\/td><td>51 (7.4%)<\/td><td><\/td><\/tr><tr><td>COVID\u201019<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Healing (909%\u201066.0%)<\/td><td>793 (87.2%)<\/td><td>109 (12.0%)<\/td><td>7 (0.8%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Death (469%\u201034.0%)<\/td><td>269 (57.4%)<\/td><td>152 (32.4%)<\/td><td>48 (10.2%)<\/td><td><\/td><\/tr><tr><td>Diabetes<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Absent (866%\u201062.8%)<\/td><td>703 (81.2%)<\/td><td>143 (16.5%)<\/td><td>20 (2.3%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Available (512%\u201032.6%)<\/td><td>359 (70.1%)<\/td><td>118 (23.0%)<\/td><td>35 (6.9%)<\/td><td><\/td><\/tr><tr><td>Kidney failure<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Absent (934%\u201067.8%)<\/td><td>808 (86.5%)<\/td><td>114 (12.2%)<\/td><td>12 (1.3%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>AKI (316%\u201022.9%)<\/td><td>186 (58.8%)<\/td><td>101 (32.0%)<\/td><td>29 (9.2%)<\/td><td><\/td><\/tr><tr><td>CRF (128%\u20109.3%)<\/td><td>68 (53.1%)<\/td><td>46 (36.0%)<\/td><td>14 (10.9%)<\/td><td><\/td><\/tr><tr><td>Blood pressure<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (810%\u201058.8%)<\/td><td>727 (89.7%)<\/td><td>76 (9.4%)<\/td><td>7 (0.9%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Hypotension (466%\u201033.8%)<\/td><td>260 (55.8%)<\/td><td>161 (34.5%)<\/td><td>45 (9.7%)<\/td><td><\/td><\/tr><tr><td>Hypertension (102%\u20107.4%)<\/td><td>75 (73.6%)<\/td><td>24 (23.5%)<\/td><td>3 (2.9%)<\/td><td><\/td><\/tr><tr><td>ALT<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (562%\u201040.8%)<\/td><td>488 (86.8%)<\/td><td>65 (11.6%)<\/td><td>9 (1.6%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>1\u20103 times (488%\u201035.4%)<\/td><td>389 (79.7%)<\/td><td>86 (17.6%)<\/td><td>13 (2.7%)<\/td><td><\/td><\/tr><tr><td>3\u20105 times (135%\u20109.8%)<\/td><td>89 (65.9%)<\/td><td>37 (27.4%)<\/td><td>9 (6.7%)<\/td><td><\/td><\/tr><tr><td>5\u201010 times (65%\u20104.7%)<\/td><td>36 (55.4%)<\/td><td>20 (30.8%)<\/td><td>9 (13.8%)<\/td><td><\/td><\/tr><tr><td>&gt;10 times (61%\u20104.4%)<\/td><td>32 (52.5%)<\/td><td>26 (42.6%)<\/td><td>3 (4.9%)<\/td><td><\/td><\/tr><tr><td>&gt;1000 (IU\/L) (67%\u20104.9%)<\/td><td>28 (41.8%)<\/td><td>27 (40.3%)<\/td><td>12 (17.9%)<\/td><td><\/td><\/tr><tr><td>AST<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (468%\u201034.0%)<\/td><td>428 (91.4%)<\/td><td>36 (7.7%)<\/td><td>4 (0.9%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>1\u20103 times (564%\u201040.9%)<\/td><td>454 (80.5%)<\/td><td>98 (17.4%)<\/td><td>12 (2.1%)<\/td><td><\/td><\/tr><tr><td>3\u20105 times (121%\u20108.8%)<\/td><td>76 (62.8%)<\/td><td>38 (31.4%)<\/td><td>7 (5.8%)<\/td><td><\/td><\/tr><tr><td>5\u201010 times (71%\u20105.1%)<\/td><td>35 (49.3%)<\/td><td>27 (38.0%)<\/td><td>9 (12.7%)<\/td><td><\/td><\/tr><tr><td>More than 10 times (45%\u20103.3%)<\/td><td>22 (48.9%)<\/td><td>16 (35.6%)<\/td><td>7 (15.5%)<\/td><td><\/td><\/tr><tr><td>&gt;1000 (IU\/L) (109%\u20107.9%)<\/td><td>47 (43.1%)<\/td><td>46 (42.2%)<\/td><td>16 (14.7%)<\/td><td><\/td><\/tr><tr><td>ALP<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (966%\u201070.1%)<\/td><td>737 (76.3%)<\/td><td>191 (19.8%)<\/td><td>38 (3.9%)<\/td><td>.092<\/td><\/tr><tr><td>1\u20102 times (234%\u201017.0%)<\/td><td>176 (75.2%)<\/td><td>45 (19.2%)<\/td><td>13 (5.6%)<\/td><td><\/td><\/tr><tr><td>More than 2 times(178%\u201012.9%)<\/td><td>149 (83.7%)<\/td><td>25 (14.0%)<\/td><td>4 (2.3%)<\/td><td><\/td><\/tr><tr><td>GGT<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (909%\u201066%)<\/td><td>722 (79.4%)<\/td><td>158 (7.4%)<\/td><td>29 (3.2%)<\/td><td>.072<\/td><\/tr><tr><td>1\u20102 times (254%\u201018.4%)<\/td><td>173 (68.1%)<\/td><td>62 (24.4%)<\/td><td>19 (7.5%)<\/td><td><\/td><\/tr><tr><td>More than 2 times (215%\u201015.6%)<\/td><td>167 (77.7%)<\/td><td>41 (19.1%)<\/td><td>7 (3.2%)<\/td><td><\/td><\/tr><tr><td>Total Bilirubin<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (1059%\u201076.9%)<\/td><td>860 (81.2%)<\/td><td>171 (16.2%)<\/td><td>28 (2.6%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>1\u20102 times (257%\u201018.6%)<\/td><td>172 (66.9%)<\/td><td>68 (26.4%)<\/td><td>17 (6.7%)<\/td><td><\/td><\/tr><tr><td>More than 2 times (62%\u20104.5%)<\/td><td>30 (48.4%)<\/td><td>22 (35.5%)<\/td><td>10 (16.1%)<\/td><td><\/td><\/tr><tr><td>LDH<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (&lt;225&nbsp;IU\/L) (161%\u201011.7%)<\/td><td>157 (97.5%)<\/td><td>4 (2.5%)<\/td><td>0 (0.0%)<\/td><td>&lt;.001<\/td><\/tr><tr><td>Normal\u20101000 (IU\/L) (969%\u201070.3%)<\/td><td>788 (81.3%)<\/td><td>158 (16.3%)<\/td><td>23 (2.4%)<\/td><td><\/td><\/tr><tr><td>1000\u20102250 (IU\/L) (148%\u201010.7%)<\/td><td>79 (53.4%)<\/td><td>55 (37.2%)<\/td><td>14 (9.4%)<\/td><td><\/td><\/tr><tr><td>&gt;2250 (IU\/L)(100%\u20107.3%)<\/td><td>38 (38.0%)<\/td><td>44 (44.0%)<\/td><td>18 (18.0%)<\/td><td><\/td><\/tr><tr><td>Lymphocyte levels<\/td><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Normal (724%\u201052.5%)<\/td><td>581 (80.3%)<\/td><td>119 (16.4%)<\/td><td>24 (3.3%)<\/td><td>.120<\/td><\/tr><tr><td>Mild lymphopenia (489%\u201035.5%)<\/td><td>360 (73.6%)<\/td><td>111 (22.7%)<\/td><td>18 (3.7%)<\/td><td><\/td><\/tr><tr><td>Severe lymphopenia (165%\u201012.0%)<\/td><td>121 (73.3%)<\/td><td>31 (18.8%)<\/td><td>13 (7.9%)<\/td><td><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0002\/?report=objectonly\">Open in a separate window<\/a><\/p>\n\n\n\n<p id=\"__p30\">Abbreviations: AKI, Acute kidney injury; ALP, alkaline phosphatase, GGT, gamma glutamyl transpeptidase; ALT, alanine transaminase; AST, aspartate transaminase; CRF, Chronic renal failure; LDH, lactate dehydrogenase.<\/p>\n\n\n\n<p id=\"__p31\">The prevalence of elevated amylase was 2.04 times higher in men than that in women. Hypotension (odds ratio [OR]: 6.63), sepsis (OR: 6.20), ischaemia\u2010related liver damage (OR: 6.63) and renal failure (OR: 5.18) were found to be significantly associated with pancreatic enzyme levels (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0003\/\">3<\/a>).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">TABLE 3<\/h3>\n\n\n\n<p id=\"__p32\">Analysis of factors affecting enzyme elevation in COVID\u201019 patients with elevated amylase and lipase<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-regular\"><table><thead><tr><th>Feature<\/th><th>Univariate<\/th><th>Multivariate<\/th><\/tr><tr><th>OR<\/th><th>95% Cl<\/th><th><em>P<\/em>&nbsp;value<\/th><th>OR<\/th><th>95% Cl<\/th><th><em>P<\/em>&nbsp;value<\/th><\/tr><\/thead><tbody><tr><td>Age<\/td><td>1.89<\/td><td>1.46\u20102.44<\/td><td>.001<\/td><td>1.72<\/td><td>1.40\u20102.11<\/td><td>.001<\/td><\/tr><tr><td>Gender<\/td><td>2.04<\/td><td>1.57\u20102.64<\/td><td>.001<\/td><td>1.86<\/td><td>1.50\u20102.31<\/td><td>.001<\/td><\/tr><tr><td>COVID\u201019 Severity<\/td><td>4.37<\/td><td>3.28\u20105.81<\/td><td>&lt;.001<\/td><td>3.76<\/td><td>2.90\u20104.88<\/td><td>&lt;.001<\/td><\/tr><tr><td>Death from COVID\u201019<\/td><td>5.08<\/td><td>3.89\u20106.64<\/td><td>&lt;.001<\/td><td>4.23<\/td><td>3.33\u20105.36<\/td><td>&lt;.001<\/td><\/tr><tr><td>Diabetes<\/td><td>1.82<\/td><td>1.41\u20102.35<\/td><td>.001<\/td><td>1.72<\/td><td>1.40\u20102.11<\/td><td>.001<\/td><\/tr><tr><td>Kidney failure<\/td><td>5.18<\/td><td>3.95\u20106.79<\/td><td>&lt;.001<\/td><td>3.78<\/td><td>3.00\u20104.75<\/td><td>&lt;.001<\/td><\/tr><tr><td>Liver damage<\/td><td>6.63<\/td><td>4.56\u20109.64<\/td><td>&lt;.001<\/td><td>3.09<\/td><td>2.43\u20103.94<\/td><td>&lt;.001<\/td><\/tr><tr><td>Hypotension<\/td><td>6.86<\/td><td>4.50\u201010.40<\/td><td>&lt;.001<\/td><td>5.67<\/td><td>3.90\u20108.22<\/td><td>&lt;.001<\/td><\/tr><tr><td>Sepsis<\/td><td>6.20<\/td><td>3.83\u201010.05<\/td><td>.008<\/td><td>2.88<\/td><td>2.24\u20103.70<\/td><td>.003<\/td><\/tr><tr><td>Pancreatitis<\/td><td>21.2<\/td><td>2.54\u2010166.7<\/td><td>.005<\/td><td>8.02<\/td><td>4.54\u201086.3<\/td><td>.026<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/table\/ijcp14692-tbl-0003\/?report=objectonly\">Open in a separate window<\/a><\/p>\n\n\n\n<p id=\"__p33\">A very strong positive correlation was found between amylase and lipase levels in all patients (<em>r<\/em>: .828,&nbsp;<em>P<\/em>&nbsp;&lt;&nbsp;.001), which implicates that the increased amylase in COVID\u201019 patients is caused by the pancreas. A weak correlation was found between amylase level and age or gender. Likewise, a weak but statistically significant correlation was found between amylase level and DM. A strong correlation was detected between the amylase level and the severity of COVID\u201019. Additionally, the presence of liver damage, renal failure, hypotension and multiple organ dysfunction syndrome (MODS) in these patients was moderately correlated with amylase level (Figure&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/figure\/ijcp14692-fig-0001\/\">1<\/a>).<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/figure\/ijcp14692-fig-0001\/\"><\/a><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/figure\/ijcp14692-fig-0001\/\">FIGURE 1<\/a><\/p>\n\n\n\n<p id=\"__p34\">Correlation between amylase level and risk factors in COVID\u201019 patients with hyperamylasaemia<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#\">Go to:<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-sec-0012title\">4.\u2003DISCUSSION<\/h2>\n\n\n\n<p id=\"__p35\">We found that 23% of patients with COVID\u201019 infection had pancreatic enzyme elevations, and we also detected a relationship between pancreatic enzyme elevation and the severity of COVID\u201019 infection, haemodynamic instability and MODS.<\/p>\n\n\n\n<p id=\"__p36\">Although 10.9% of patients with mild COVID\u201019 infection had elevated amylase levels, this rate was 34.9% in patients with severe COVID\u201019 infection. It was also revealed that the causes of pancreatic enzyme elevation were hypotension and ischaemia in patients with severe COVID\u201019 infection. Elevated amylase levels were detected in 10.3% and 44.2% of patients with a normal MAP and low MAP (&lt;60&nbsp;mmHg), respectively. Out of 316 patients with a high amylase level, 36.7% of the patients recovered and 63.3% of them died. Moreover, 53% of patients with ischaemic hepatitis had both amylase and lipase elevations. We consider that after the development of shock in the body, pancreatic damage occurs in addition to hepatic and intestinal injury as a result of the decrease in blood flow to the gastrointestinal system.<\/p>\n\n\n\n<p id=\"__p37\">A study investigating the relationship between COVID\u201019 infection and pancreas reported pancreatic damage in 1%\u20102% and 17% of patients with mild and severe infection, respectively. The authors suggested that pancreatic damage can be exacerbated by systemic inflammation.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0014\">14<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0015\">15<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0016\">16<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0017\">17<\/a>&nbsp;Amylase and lipase elevation suggestive of pancreatic damage has been reported in 8.5%\u201017.3% of patients with COVID\u201019. Moreover, higher enzyme levels have been reported in severe COVID\u201019 patients.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0014\">14<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0015\">15<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0016\">16<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0017\">17<\/a>&nbsp;Likewise, in two previous autopsy studies, five of 11 (45.5%) and two of eight (25%) cases were detected with focal pancreatitis with haemorrhagic and necrotic changes in the pancreas. These changes had no clinical manifestations and were attributed to ischaemia and end\u2010organ damage.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0018\">18<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0019\">19<\/a>&nbsp;In the light of our data, we consider that pancreatic damage is the most important cause of amylase and lipase elevations. The exact pathophysiology of pancreatic damage remains unclear, while the most widely accepted hypothesis points to pancreatic ischaemia.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0020\">20<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0021\">21<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0022\">22<\/a>&nbsp;If septicaemia progresses towards septic shock, not only in COVID\u201019 but also in other infections, the resulting hypotension and vasodilation reduce blood flow to organs. To protect blood flow to vital organs such as the brain and heart, blood flow to the celiac, superior and inferior mesenteric arteries are reduced as a part of the protective mechanism. Afterwards, this is followed by renal and iliac arteries. This is the neurohormonal mechanism protecting vital organs. Gastrointestinal system is the target organ of shock and hypotension. As a result, the blood flow to the liver, pancreas and the entire gastrointestinal system is reduced, thereby causing symptoms such as nausea, vomiting, distension, ileus, or diseases such as ischaemic hepatitis.<\/p>\n\n\n\n<p id=\"__p38\">Pancreas is supplied well by pancreatic arteries that stem from the splenic, gastroduodenal and superior mesenteric arteries. Amylase, lipase, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) are released into the bloodstream caused by the ischaemia resulting from decreased blood flow to the pancreas.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0023\">23<\/a>&nbsp;This damage is mainly caused by haemodynamic deterioration, not by the virus itself. Similarly, in our study, elevated amylase and lipase levels were found to be associated with haemodynamic parameters and hypotension.<\/p>\n\n\n\n<p id=\"__p39\">Although increased amylase and lipase levels might have clinical importance, it seems highly unlikely to use these parameters as prognostic indicators in clinical practice, mainly because enzyme elevation occurs during the intensive care period when the disease is severe and requires mechanical ventilation. At this stage, most patients have single or multiple organ failure and require vasopressor support.<\/p>\n\n\n\n<p id=\"__p40\">In conclusion, although ACE2 receptors are expressed highly in pancreatic tissue, pancreatic enzyme elevations occurring in COVID\u201019 infection might be associated with the severity of disease and haemodynamic instability. If the opposite was the case, we would have seen too many cases of pancreatitis, mainly because the pancreas has ACE2 receptors. As a matter of fact, despite the huge number of COVID\u201019 cases, which has exceeded 100 million, pancreatitis has remained only at the level of case reports.<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0024\">24<\/a>,&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#ijcp14692-bib-0025\">25<\/a><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/#\">Go to:<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"notes-1title\">Notes<\/h2>\n\n\n\n<p id=\"__p5\">Bacaks\u0131z F, Ebik B, Ekin N, K\u0131l\u0131c J.&nbsp;Pancreatic damage in COVID\u201019: Why? How?&nbsp;<em>Int J Clin Pract<\/em>. 2021;00:e14692. 10.1111\/ijcp.14692&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8420122\/\">PMC free article<\/a>]&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34331821\">PubMed<\/a>] [<a href=\"https:\/\/dx.doi.org\/10.1111%2Fijcp.14692\" target=\"_blank\" rel=\"noreferrer noopener\">CrossRef<\/a>]&nbsp;[<a href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Int+J+Clin+Pract&amp;title=Pancreatic+damage+in+COVID%E2%80%9019:+Why?+How?&amp;volume=00&amp;publication_year=2021&amp;pages=e14692&amp;doi=10.1111\/ijcp.14692&amp;\" target=\"_blank\" rel=\"noreferrer noopener\">Google Scholar<\/a>]<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-sec-0016title\">DATA AVAILABILITY STATEMENT<\/h2>\n\n\n\n<p id=\"__p43\">Data may be made available upon request to the corresponding author.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"ijcp14692-bibl-0001title\">REFERENCES<\/h2>\n\n\n\n<p>1.&nbsp;Vedel AG, Holmgaard F, Rasmussen LS, et al.&nbsp;Perfusion Pressure Cerebral Infarct (PPCI) trial \u2010 the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial.&nbsp;<em>Trials<\/em>. 2016;17:247.&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4869311\/\">PMC free article<\/a>]&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27189028\">PubMed<\/a>]&nbsp;[<a rel=\"noreferrer noopener\" href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Trials&amp;title=Perfusion+Pressure+Cerebral+Infarct+(PPCI)+trial+%E2%80%90+the+importance+of+mean+arterial+pressure+during+cardiopulmonary+bypass+to+prevent+cerebral+complications+after+cardiac+surgery:+study+protocol+for+a+randomised+controlled+trial&amp;volume=17&amp;publication_year=2016&amp;pages=247&amp;pmid=27189028&amp;\" target=\"_blank\">Google Scholar<\/a>]<\/p>\n\n\n\n<p>2.&nbsp;Chai X, Hu L, Zhang Y, et al.&nbsp;Specific ACE2 expression in cholangiocytes may cause liver damage after 2019\u2010nCoV infection.&nbsp;<em>BioRxiv<\/em>. 2020:4\u201316.&nbsp;[<a rel=\"noreferrer noopener\" href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=BioRxiv&amp;title=Specific+ACE2+expression+in+cholangiocytes+may+cause+liver+damage+after+2019%E2%80%90nCoV+infection&amp;publication_year=2020&amp;pages=4-16&amp;\" target=\"_blank\">Google Scholar<\/a>]<\/p>\n\n\n\n<p>3.&nbsp;Furong L, Xin Long BZ, Wanguang ZXC, Zhanguo Z.&nbsp;ACE2 expression in pancreas may cause pancreatic damage after SARS\u2010CoV\u20102 infection.&nbsp;<em>Clin Gastroenterol Hepatol<\/em>. 2020;18:2128\u20102130.e2.&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7194639\/\">PMC free article<\/a>]&nbsp;[<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32334082\">PubMed<\/a>]&nbsp;[<a rel=\"noreferrer noopener\" href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Clin+Gastroenterol+Hepatol&amp;title=ACE2+expression+in+pancreas+may+cause+pancreatic+damage+after+SARS%E2%80%90CoV%E2%80%902+infection&amp;volume=18&amp;publication_year=2020&amp;pages=2128-2130.e2&amp;pmid=32334082&amp;\" target=\"_blank\">Google Scholar<\/a>]<\/p>\n\n\n\n<p>4.&nbsp;Yang JK, Feng Y, Yuan MY, et al.&nbsp;Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS.&nbsp;<em>Diabet Med<\/em>. 2006;23:623\u2010628. 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