ABSTRACT
Background: Kidney injury molecule-1 (KIM-1), a type-1 transmembrane glycoprotein, has been well studied as a specific injury marker for proximal tubules (PT). KIM-1 functions as a receptor for apoptotic fragments through a phagocytic process. KIM-1 (also called TIM-1) serves as a receptor for hepatitis A virus and Ebola virus, and possibly for severe respiratory syndrome-coronavirus (SARS-CoV-1). During the pandemic spread of coronavirus disease 2019 (COVID-19), many patients have suffered from acute kidney injury (AKI) as well as lung damage, Viral upkake has been attributed to interactions with ACE2, a receptor for the virus. The goal of this study was to investigate whether there is kidney histological data that KIM-1 may also serve as a receptor for SARS-CoV-2 to infect the PT. Methods: Two patients (one adult and one child) who died of COVID19 and 10 patients with AKI but no COVID19 (control group) were included in the study. All kidney tissue sections were stained for KIM-1 (monoclonal AKG7 antibody) and scored from 0 to 3+. Electron microscopy was conducted using kidney tissue of the COVID19+ patients. Results: Both COVID19+ patients had normal pre-mortem levels of serum creatinine (sCr) (adult 0.63 and child 0.17 mg/dl), whereas the control cases all had elevated sCr (1.9 to 10.7 mg/dl). Control renal biopsies revealed positive KIM-1 staining ranging from 1+ to 3+ along the surface of PT in a patchy pattern involving 20 to 80% of the cortex;no cytoplasmic granular materials were identified. By contrast, the KIM-1 staining in COVID19+ kidneys revealed spotty granular staining in the cytoplasm and diffuse surface 2+ to 3+ staining in most PTs, while glomeruli stained negatively for KIM-1 as internal negative controls. In the two COVID19+ patients, SARS-CoV-2 particles showed spiking-crown appearances with sizes ranging from 70 to 110 nm in the PT cytoplasm by ultrastructural studies. Conclusions: Our initial evidence suggests there is an atypical staining pattern of KIM-1 in the PT of COVID19+ patients, raising a possibility that KIM-1 may serve as a receptor for SARS-CoV-2. KIM-1 may also serve to internalize the virus into the PT. In addition the two COVID+ patients had normal sCr levels but positive KIM-1 staining, indicating that sCr underestimates renal injury caused by SAR-CoV-2 infection.
ABSTRACT
We present the case details of seven patients diagnosed with severe novel coronavirus disease 2019 (2019-nCoV, hereafter COVID-19) with hepatic injury. Most of these patients were elderly and had hypertension, diabetes mellitus, coronary heart disease, and other underlying health conditions prior to admission for COVID-19. Liver injury occurred in all seven cases during the course of the disease. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels initially increased (1.2-times to 2.0-times the normal value, respectively) in the second week. The liver function recovered in all patients within one week of conventional liver protection treatment. Elevated serum transaminase levels in these patients were due to the COVID-19 infection but could also be related to systemic immune response caused by cytokine storm syndrome (CSS) and hepatocyte damage caused by ischemia and hypoxia. COVID-19 is highly infectious and mainly affects the lungs. In some cases, especially in patients with severe disease type, COVID-19 may also cause liver injury. The liver function of patients with severe COVID-19 should be very carefully monitored, especially if the patients are elderly and have underlying comorbidities.