High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?
Abstract
:1. Introduction
2. Methods
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 | Case 9 | Case 10 | Case 11 | Case 12 | Case 13 | Case 14 | Case 15 | Case 16 | Case 17 | Case 18 | Case 19 | Case 20 | Case 21 | Case 22 | Key Findings Summary for Cases 1–22 | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age, race biological sex | 57y Cn M | 79y Cn M | 48y Cn F | 82y A-C/ mixed race M | 57y A-C M | 89y Cn M | 81y A-C M | 72y Cn M | 92y Cn M | 48y Cn M | 76y Cn M | 42y A-C F | 83y A-C M | 86y Cn F | 85y Cn F | 67y Cn F | 57y A-C F | 94y Cn F | 56y Cn M | 65y Cn M | 69y Cn F | 59y Cn M | 14/22 (64%) M; mean age 70y (SD: 16); 16/22 (73%) Cn | |
Diagnosis of COVID-19 | History & histol | History & histol | AM RNA test | History & histol | History & histol | AM RNA test | AM RNA test | AM RNA test | AM RNA test | History & histol | History & histol | PM lung RNA test | AM RNA test | AM RNA test | PM RNA test | Histol | Histol | Histol | PM RNA test | Histol | AM RNA test | PM lung RNA test | ||
MCCD section I (a): Disease or condition leading directly to death | ARDS | ARDS | Cardiac arryth-mia | PE & viral Pu, consis-tent with COVID-19 | PE | Acute bacterial Pu | Viral Pu with features consis-tent with COVID-19 | COVID-19 infection | COVID 19 | GI haemo-rrhage, ARDS, excess-ive blood levels of meth-adone | RHF leading to cardiac arrhyth-mia | PE | PTE & COVID-19 | COVID-19 & bacterial BPu | COVID-19 & IHD | Hypoxic brain injury, multi-organ failure | COVID-19 | Acute bacter-ial Pu | Multi-ple bil-ateral PTE | COVID-19 | COVID-19 | COVID-19 pneu-monitis | 6/22 (27%) thrombo-embolic complica-tion of COVID-19 included in MCCD Part I | |
MCCD section I (b): Disease/ condition leading to I (a) | Pu | Pu | RHF | DVT | DVT | COVID-19 pneumo-nitis and aspirat-ion of food material | n/a | n/a | n/a | COVID-19 | Pulm-onary artery thromb-osis | DVT | DVT | n/a | n/a | Cardiac arrest due to arrhyth-mia | n/a | COVID-19 | DVT | n/a | n/a | n/a | ||
MCCD section I (c): Disease/ condition leading to I (b) | n/a | n/a | OPu, mild lympho-cytic myo-carditis | n/a | Mild lympho-cytic Pu, consis-tent with resolving COVID-19 | n/a | n/a | n/a | n/a | n/a | ARDS/ viral pneu-monitis, consis-tent with COVID-19 | COVID-19 | n/a | n/a | n/a | n/a | n/a | n/a | COVID-19 | n/a | n/a | n/a | ||
MCCD section II: Contribut-ing to but not directly causative of death | n/a | n/a | T2DM, hypo-thyroid-ism and Rett’s syn-drome | DM, demen-tia, frailty | n/a | IHD, Parkin-son’s disease | CHF, IHD, T2DM, CKD | IHD, T2DM, CKD | ILD, COPD, iron deficien-cy anaemia, IHD, aortic valve disease | n/a | n/a | n/a | CKD | CHF, AF, IHD, COPD | n/a | Bilateral BPu, arising on a back-ground of COVID-19 | n/a | n/a | n/a | n/a | n/a | HTN | ||
Past medical history in addition to MCCD | HTN, high chol-esterol, prostat-ectomy, gout | IgG MGUS, AF, HTN, border-line DM, CKD, spinal degen-eration, neuro-pathy | Nil addit-ional | HTN, T2DM | not known | AF, CABG ×3 | End stage CKD, vascular demen-tia, stroke, HTN, epilepsy, blind-ness, cataracts, divertic-ular disease, gout | High chol-esterol, duo-denal ulcera-tion, IBS, MI, CABG ×4, PF | Demen-tia | not known | Uro-sepsis, AKI, Alz-heimer’s & vascular demen-tia, falls, T2DM | HTN | T2DM, HTN, Stage 3 CKD | Re-current UTIs, osteo-porosis | Drug eluting CA stent, hip replace-ment | Asthma, scoliosis, osteo-arthritis, cholecyst-ectomy | not known | not known | not known | Obesity, HTN, T2DM | CKD, hyper-thyroid-ism, HTN, arthritis, gout, major depress-ion | not known | 8/16 (50%) HTN; 8/16 (50%) DM; 6/16 (38%) arterio-path | |
BMI (kg/m2) | 27.2 | 31.3 | 24.8 | 16.8 | 29.0 | 19.2 | 19.4 | 30.3 | 19.4 | 21.0 | 18.4 | 32.5 | 24.4 | 23.2 | 19.2 | 25.2 | 38.2 | 21.4 | 26.7 | 27.5 | 20.0 | 35.6 | Mean 25, S.D. 5.9 | |
Cardiovascular | Heart weight/g (cent-ile) | 400 (50–90) | 610 (>97) | 320 (50–90) | 355 (>97) | 460 (>97) | 450 (>97) | 350 (>97) | 799 (>97) | 508 (>97) | 330 (90–97) | 380 (90–97) | 425 (>97) | 500 (>97) | 270 (10–50) | 460 (>97) | 320 (50–90) | 455 (50–90) | 280 (10–50) | 510 (>97) | 354 (10–50) | 425 (90–97) | 845 (>97) | 12/22 (55%) >97; 3/22 (14%) 90–97; 4/22 (18%) 50- 90 |
CA sten-osis | + | N.S. | N.S. | + | + | +++ | +++ | +++ | ++ | + | + | N.S. | ++ | ++ | ++ | ++ | + | ++ | ++ | + | N.S. | + | 3/22 (14%) +++; 9/22 (41%) ++ to +++ | |
Ventri-cles | Dilated L+/R++, sub-endo-cardial pallor | LVH | Dilated L++/ R+++, pallor, MNI+ | Dilated L++/ R+++, pallor | Dilated L+, pallor, MNI+ | Dilated L+++/ R+++, MH+++, MF++ | Dilated L+++/ R+++, MH++, MF++ | Dilated L+++/ R+++, MH+, MF+++, peri-cardial fibrosis +++ | Dilated L++/R++, sub-endo-cardial pallor, MF++ | Dilated L+++/ R+++; MNI+++ | Dilated L+++/ R+++, MF+ | Dilated L++/R++, pallor | LVH, dilated L+/R++ | Dilated L++/R++ | Dilated L+++/ R+++, pallor, MF+ | Dilated L++/R+++; MF+ | Border-line LVH | Dilated L+/R+++ | LVH, dilated R+++ | Dilated L++/R++, MF+, scattered neutro-phil infiltrate | Dilated L+/R+++, pallor | LHV, dilated L+++, MH+, MF++ | 20/22 (91%) >++ dilation. 9/22 (41%) IHD; 8/22 (36%) pallor | |
Aortic athero-scler-osis | N.S. | N.S. | N.S. | + | + | +++ | +++ | ++ | N.S. | N.S. | + | N.S. | ++ | ++ | ++ | ++ | + | + | + | ++ | + | +++ | 9/22 (41%) ++ to +++ | |
Respiratory | Key macro-scopic | ARDS | ARDS | ARDS, PO | ARDS, PO, PEs | ARDS, haemorr-hage, pus, PEs | ARDS, pus | ARDS, PO | ARDS, Pl adhes-ions | ARDS, emphy-sema, Pl eff, PEs | ARDS, emphy-sema, Pl eff, PEs | ARDS, Pl eff, PEs | PO, possible ARDS | Em-balmed, PEs, possible ARDS | Consoli-dation, possible ARDS, pus, PF, Pl adhes | ARDS | Consoli-dation, possible ARDS, pus, PO, Pl adhes, PEs | ARDS | ARDS, bronch-itis | ARDS, PO, PEs | ARDS, PO | ARDS, PO | ARDS, PO | 22/22 (100%) ARDS (macro &/ micro); 8/22 (36%) PE |
Key micro-scopic | ARDS +++ | ARDS + | OPu+++ | ARDS +, OPu+++ | OPu+ | OPu+, arterial recanalis-ation+, pHTN+ | ARDS +++ | ARDS +++, arterial recanalis-ation+, pHTN+ | OPu+, PF+, pHTN+ | ARDS +++, BPu+ | ARDS +, PF+, pHTN+, old infarcts+ | ARDS + | ARDS +++, OPu+ | ARDS +, OPu++ | ARDS +, PF+, emphy-sema+ | ARDS +, OPu+ | ARDS +++, BPu+ | ARDS +++, BPu+, emphy-sema+ | n/e | ARDS +++, multi-nuclear macro-phages ++, thrombi, hyper-inflation | ARDS +, OPu+, hyper-inflation | ARDS +++, viral inclus-ions (type 2 pneum-ocytes) | ||
Liver | S(ma)+ | C | VC+++ | n/e | n/e | S(ma)+, VC+, C, PL0 | VC+++ | S(ma) +++, C | VC+++ | Ischae-mic; PL0, paren-chymal L0 | VC++, PL0 | S(ma) +++ | S(ma)+, C | Normal | S(ma)+ | S (ma)++, ischaemic | S(ma) +++ | S(ma)+, VC+ | n/e | S(ma)+++ | S(ma)+, VC+++ | S(ma)+ | 12/19 (63%) S(ma); 5/19 (26%) VC++/ +++; 4/19 (21%) C |
System | Site/Feature | Key Findings (Positive and Negative) |
---|---|---|
Cardiovascular | Pericardium | Effusion [17,19,55]; fibrinous pericarditis [23] |
Heart weight & chambers | Cardiomegaly/chamber hypertrophy [18,19,21,23,24,25,26,27,34] Chamber dilatation [17,18,19,20,21,22,26] | |
Myocardial ischaemia | Infarction [24,27,31,56]; focal ischaemia, not otherwise specified [18] Scarring/ fibrosis [21,22,23,29,30,34,35] | |
Cardiac inflammation | Lymphocytic myocarditis [23,25,28,29,33,35,55] Chronic inflammatory cells without myocarditis [18,23,26,36] | |
Atherosclerosis | Significant coronary artery atherosclerosis [23] Atherosclerosis, not otherwise specified [22,24,27,28,29] | |
Vascular abnormalities (multiple systems) | Vasculitis | Endothelialitis of heart, small bowel, lung [55]; fibrinoid alteration (exact location not specified) [35] |
Microthrombi | Lung, glomeruli, spleen, heart, dermis, testis, liver sinusoids [35] | |
Macroscopic thromboemboli | Deep venous [27]; pulmonary [18,21,29,38] | |
Respiratory | Pleura and pleural cavity | Effusions [17,19,21,23,25,32,41,43]; pleuritis [51]; thickening [17,19,21]; adhesions [23,30] Subpleural petechiae [36] |
Lung weights | Elevated [17,18,19,20,21,22,23,28,29,36,37,39,40,41,51,55] | |
Lung cut surface | Red, consolidated, solidified [18,19,22,24,26,27,28,29,30,36,37,39,41,42,51,55,58] Haemorrhage [27,36]; oedema [23]; necrosis [27]; collapse [43] New fibrosis, extensive [23,38] Pre-existing structural lung disease [23,25,27] | |
Airways | Upper airway inflammation [23,27,29,40,51,67] Bronchial inflammation [21,22,28,29,40,44,45,55] with mucus [19,26,30,40,46] Small airway acute inflammation (bronchopneumonia) [23,24,25,26,27,29,36,49] Aspiration pneumonia [40] No inflammation [17,32,37,40] | |
Alveoli/interstitium | Diffuse alveolar damage/ARDS spectrum [17,18,19,20,21,22,23,24,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51] Fibrosis [25,43,48,51] Lobar pneumonia [23] Chronic inflammatory cell infiltrate [17,18,19,22,23,24,27,28,29,30,33,34,39,41,42,47,49,56] Features suggestive of viral cytopathic effect [18,19,23,28,30,33,34,35,37,42,43,48,51] | |
Vascular | Thrombosis with microangiopathy [18,19,20,21,22,24,27,28,31,35,37,39,45,46,47,49] Thrombosis [24,26,36,38,40,42,48,59] Small vessel fibrinoid necrosis [34] Severe endothelial injury with intracellular virus by EM [20,39] Neutrophilic & exudative capillaritis [18,20,21,22,29,32,33,45,46,47,48] Lymphocytic vasculitis [51] No vasculitis [49]; no thrombi [23] | |
Kidneys | Vascular | Pallor/ shock/ ischaemia [24,27,41,61,62]; infarction [24,27,62]; medullary congestion [41] Arteriolar & arterial fibrin thrombi [31,61] Microthrombi in glomeruli1 [7,22,24,31,35,61] Glomerular capillary congestion [51,61] Peritubular capillary congestion [51,61] |
Tubulo-interstitial | Acute tubular injury/ necrosis [21,24,28,35,42,44,51,60,61,62] ACE2 expression upregulated in proximal tubules [61] Acute tubulointerstitial nephritis61; no interstitial nephritis [62] | |
Other | Nephrosclerosis [18,21,23,32,40,60] Other chronic kidney/ glomerular disease [24,35,40,43,60,61] Pyelonephritis [61] | |
Lymphoreticular | Spleen | Splenomegaly [18,20,23,27,37,50]; congestion [18,21,29,37,50]; diffluence [50] Red pulp infarction [50]; red pulp lymphoplasmacytic infiltrate [18] Atrophy [18,21,28,35,37,50]; white pulp hyperplasia [50] Haemophagocytosis [17,50] Acute splenitis (concurrent bronchopneumonia) [24] |
Lymph nodes & bone marrow | Hilar & mediastinal lymphadenopathy [21,24,50] & with haemophagocytosis [50] Lymph node haemophagocytosis (site not stated) [17]; no lymph node haematophagocytosis [50] Bone marrow haematophagocytosis [49]; no bone marrow haematophagocytosis [50] | |
Adrenal glands | Shocked appearance [25]; microscopic haemorrhage [37]; zona reticularis hyperplasia [21] Acute fibrinoid arteriolar necrosis [64] No adrenal abnormalities [50] |
Pathology | Ref & Frequency Where Ascertainable | Applied Interpretation | |||
---|---|---|---|---|---|
Fibrosis | Periportal | 3/11 [21] | 29/48 [59] | Pre-existing hepatic disease | |
Incomplete septa | 3/11 [21] | 8/48 [59] | |||
Cirrhosis | 4/80 [29] 1/2 [32] | ¼ [34] | |||
Steatosis | Centrilobular | 1/1 [22] | ½ [32] | Likely pre-existing alcoholic/non-alcoholic (e.g., obesity or diabetes-related) fatty liver disease | |
Macrovesicular only | 1/4 [34] | 1/7 [33] 1/48 [59] | |||
Microvesicular only | 3/48 [60] | ||||
Mixed macrovesicular & microvesicular | 5/7 [33] 1/1 [36] | 2/2 [43] 22/48 [59] | |||
Not further specified | 1/4 [20] 11/11 [21] 1/9 [23] 7/17 [24] 1/10 [25] | 2/12 [27] 1/1 [55] 9/14 [28] 6/10 [35] | |||
Congestion | 1/4 [20] 8/11 [21] 4/9 [23] 2/12 [27] 1/1 [55] | 11/14 [28] 4/80 [29] 7/7 [33] 10/10 [35] 1/1 [41] | Right-sided cardiac failure (may be secondary to effects of COVID-19 or may represent evidence of pre-existing cardiorespiratory disease) | ||
Hepatocyte injury | Cellular death | Not further specified | 0/4 [20] | 1/3 [56] | Various causes |
Alcohol/ non-alcohol related steatohepatitis | 3/17 [24] | ||||
Massive | 1/11 [21] | Seen in severe hepatic injury due to a variety of causes | |||
Patchy/ focal | 2/11 [21] 7/7 [33] | ¼ [34] 2/2 [43] | May be seen in acute viral hepatitis (“spotty necrosis”; usually associated with lymphocytes) | ||
Periportal & centrilobular | 1/4 [34] | Periportal necrosis may be due to interface hepatitis. Centrilobular necrosis is attributable to hypoperfusion injury but may also be seen in drug and toxin-mediated injury | |||
Centrilobular | 4/11 [21] 5/17 [24] 4/14 [28] | 3/10 [35] 1/1 [36] | |||
Mild ballooning degeneration | 4/7 [33] | May be seen in cholestasis or marked hepatitis | |||
Kupffer cell activation | 2/4 [20] 10/10 [21] 1/4 [34] | 2/2 [43] 5/10 [35] | Non-specific finding secondary to hepatocyte injury | ||
Syncytial hepatocytes | 2/2 [43] | Non-specific finding secondary to hepatocyte regeneration | |||
Inflammation | Not further specified | 0/4 [20] | No evidence of hepatitis | ||
Lymphoplasmacytic, not further specified | 1/1 [22] | Seen in a variety of pathologies including resolving acute hepatitis, autoimmune hepatitis, hepatitis B/C, biliary disease | |||
Parenchymal | Lobular lymphocytic | 2/4 s [34] 24/48 [59] | May be seen in acute viral hepatitis (CMV, EBV), autoimmune hepatitis, and primary biliary cholangitis | ||
Lobular lymphocytic & neutrophilic | 1/2 [43] | Neutrophilic inflammation may be seen in steatohepatitis (especially alcohol-related) | |||
Lobular neutrophilic | 1/14 [28] | ||||
Sinusoidal neutrophilic | 6/10 [35] | ||||
Neutrophil microabscess | 1/1 [41] | Seen in human cytomegalovirus (CMV) infection but may also be seen in other settings, such as ascending cholangitis and seeding from a septic source | |||
Not specified | 0/1 [36] | ||||
Periportal | Lymphocytic | 8/11 [21] 4/14 [28] 1/4(C/SLL) [34] | 1/2 [43] 32/48 [59] | May be seen in a wide variety of hepatitises | |
Lymphoplasmacytic | NS/10 (“minimal”) [25] | ||||
Not specified | 7/7 [33] 0/1 [36] | 9/10 [35] | |||
Vascular | Lymphocytic endothelialitis | 1/3 [56] | |||
Sinusoidal abnormalities | Dilatation | 7/7 [33] | 2/4 [34] | Seen in hypercoagulability syndromes and venous flow abnormalities | |
Intrasinusodal fibrin thrombi | 1/10 [35] 0/2 [43] | 13/48 [59] | Non-specific finding implicated in the pathogenesis of hepatic congestion | ||
Ductal/canalicular abnormalities | Cholestasis | 8/11 [21] 2/7 [33] | 0/2 [43] | Non-specific finding that may be seen in sepsis amongst other aetiologies | |
Ductular reaction with lymphocytic inflammation | 7/11 [21] | Non-specific finding secondary to acute biliary obstruction | |||
Ductular reaction without inflammation | 1/11 [21] | ||||
Haemophagocytosis | 1/4 [20] | 0/4 [50] | Non-specific finding that may be seen in sepsis and other systemic haemophagocytic disorders | ||
Thrombosis | 1/11 [21] 35/48 [59] | Implies a pro-coagulant state (systemic/ localised) | |||
Macroscopic impression of liver shock | 3/12 [27] | NS/80 [29] | Secondary to hypoperfusion | ||
Hepatomegaly (aetiology not specified) | 1/1 (“minimal”) [22] | 1/4 [27] 0/4 [50] | Significance uncertain |
PM Cohort | Steatosis | Venous Congestion | Cirrhosis |
---|---|---|---|
COVID-19 PM cases in our study (Table 1) | 12/19 (63%) p < 0.05 | 5/19 (26%) p > 0.05 | 4/19 (21%) p < 0.00001 |
COVID-19 PM cases in published studies (Table 3) | 80/164 (49%) p < 0.0001 | 54/160 (34%) p < 0.00001 | 9/97 (9.3%) p < 0.001 |
COVID-19 PM cases in our study and published studies | 92/183 (50%) p < 0.00001 | 59/179 (33%) p < 0.00001 | 13/116 (11%) p < 0.00001 |
Aggregate data derived from all pre-pandemic PM studies detailed in the rows below | 682/2067 (33%) | 53/341 (16%) | 47/1843 (2.6%) |
Unnatural causes of death, including sudden death and car accidents [70] | 156/498 31.% | Not measured | 6/498 1.2% |
Non burn trauma [76] | 108/224 48% | Not measured | |
Multiple causes: trauma (35%), acute myocardial infarction (30%), opiate overdose (13%), cerebrovascular accidents (4%), infectious diseases (3%) and others (15%) [71] | 283/896 31.6% | Not measured | 7/896 (0.8%) |
Causes of death listed as “diverse”. Paper specifies that liver disease was not primary cause of death in any included case. NB this was a study of dissection room cadavers, not autopsies [72] | 24/68 35% | Not measured | 3/68 4.4% |
Cardiovascular diseases 68%, respiratory illnesses 25%, gastrointestinal disorders 5% and cerebrovascular disease 2% [76] | 6/40 15% | Not measured | 3/40 7.5% |
Road/railway accidents, burns, drowning, hanging and poisoning [71] | 24/70 34% | 19/70 27% | 8/70 11% |
Road accidents, poisoning [73] | 25/100 25% | 12/100 12% | 4/100 4% |
Medicolegal autopsies [74] | 46/121 38% | 9/121 7.4% | 8/121 6.6% |
Road traffic Accidents (n = 35), poisoning (n = 5), hanging (n = 3), suspicious death (n = 1), Myocardial infarction (n = 2), drowning (n = 2), burns (n = 1) and on railway (n = 1) [75] | 10/50 20% | 13/50 26% | 8/50 16% |
Length of Patient Admission (days) | Abnormal Albumin on Admission | p Value (Chi Squared) for Significance of Abnormal vs. Normal Albumin Compared with Poorer Patient Outcomes | Albumin Level (g/L) Mean ± SD [Normal Range: 35–50 g/L] | Abnormal Alanine Transaminase (ALT) on Admission | p Value (Chi Squared) for Significance of Abnormal vs. Normal ALT Compared with Poorer Patient Outcomes | Alanine Transaminase (iU/L) Mean ± SD [Normal Range: 10–49 iU/L] |
---|---|---|---|---|---|---|
<7 | 38/54 (70.4%) | 0.00043 | 29 ± 3.9 | 16/54 (26.6%) | 0.42 | 76.8 ± 45.3 |
7–13 | 46/52 (88.5%) | 0.020 | 27.8 ± 4.1 | 13/52 (25.0%) | 0.55 | 93.7 ± 59.8 |
14–20 | 37/43 (86.0%) | 0.028 | 26.8 ± 3.7 | 14/43 (32.6%) | 0.15 | 98.5 ± 133.6 |
>21 | 35/39 (89.7%) | 0.081 (All survivors vs. deceased) | 24.5 ± 5.8 | 13/39 (33.3%) | 0.0135 (All survivors vs. deceased) | 66.2 ± 29.2 |
Deceased | 80/88 (90.9%) | 24.6 ± 5.8 | 14/88 (15.9%) | 101.1 ± 88.7 | ||
Total | 236/276 (85.5%) | 26.2 ± 5.2 | 70/276 (25.3%) | 87.3 ± 78.6 | ||
One-way ANOVA p value | 0.000012 | 0.73 |
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Hirayama, Y.; Daniels, N.F.; Evans, S.; Clarke, D.; Purvis, S.; Oliver, C.; Woodmansey, S.; Staniforth, J.; Soilleux, E.J. High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor? Diagnostics 2021, 11, 1703. https://doi.org/10.3390/diagnostics11091703
Hirayama Y, Daniels NF, Evans S, Clarke D, Purvis S, Oliver C, Woodmansey S, Staniforth J, Soilleux EJ. High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor? Diagnostics. 2021; 11(9):1703. https://doi.org/10.3390/diagnostics11091703
Chicago/Turabian StyleHirayama, Yuri, Natasha Faye Daniels, Shelley Evans, David Clarke, Stephenie Purvis, Charlotte Oliver, Stephen Woodmansey, Joy Staniforth, and Elizabeth J. Soilleux. 2021. "High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?" Diagnostics 11, no. 9: 1703. https://doi.org/10.3390/diagnostics11091703