Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Abstract

BACKGROUND The outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODS We conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) and in situ expression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM). RESULTS 27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22% vs 24.19%, p< 0.001; 69.57% vs 11.29%, p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses- like particles are visible in the kidneys. Viral infection not only induces CD68+ macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules. CONCLUSIONS SARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+ macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.

Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients

“…of SARS-CoV-2 were very high in nasopharyngeal swab during the first week of symptoms, with peak on day 4 post-onset, whereas the peak value appeared until 7-10 days post-onset with much lower RNA copies during SARS-CoV and MERS-CoV infection [6,[18][19][20]. Second, the presence of virus RNA in lower respiratory tract (sputum or BALs), stool, and blood samples were reported, and the kinetics of virus shedding in these sites were distinct from that in throat [8][9][10][11]. Third, sampling error and the technical limitations of RT-PCR sometimes led to a false testing result [21].…”

“…However, pathogenic cure in terms of viral RNA-conversion, had to be reached before patients being discharged from hospitals for the purpose of disease control, at least in China. The kinetics of viral shedding [6,7], the possible presence of viral RNA in multiple sites [8][9][10][11], sampling error and the technical limitations of RT-PCR sometimes led to a false testing result [12,13], posing a great challenge to discharge management after obtaining clinical cure. Nevertheless, a recent investigation reported that the median duration of viral shedding was 20 days after disease onset for patients infected with SARS-CoV-2 [4].…”

SARS-CoV-2 (COVID-19) and intravascular volume management strategies in the critically ill

“…In these patients, early aggressive volume resuscitation is indicated to avoid development of extensive acute tubular injury due to prolonged severe renal hypoperfusion. While it has been suggested that direct cellular injury via ACE-2 that is expressed in proximal renal tubules could contribute to AKI, 21 it remains likely that shock (and in some cases cytokine storm) are the primary causes of acute tubular necrosis in this setting. Moreover, similar to right-sided heart failure, following aggressive fluid administration the increased right atrial pressure is transmitted retrograde, leading to elevated venous pressure in abdominal organs such as the kidney, liver, and the guts.…”

Remdesivir inhibits renal fibrosis in obstructed kidneys

“…Indeed, a clinical study reported that 27.06% of patients with COVID-19 exhibited acute renal failure (ARF), while elderly patients (≥60 years) were more likely to develop ARF (65.22% vs 24.19%) (8). A further immunohistochemistry analysis revealed that the antigen for 2019-nCoV accumulates in renal tubules (8). Another clinical study with 59 COVID-19 patients showed that proteinuria occurred in 63% of patients (9).…”

“…It has been found that ACE2 is highly expressed in renal tubular cells, implying that 2019-nCoV may directly bind to ACE2-positive cells in the kidney and thus induce kidney injuries (7). Indeed, a clinical study reported that 27.06% of patients with COVID-19 exhibited acute renal failure (ARF), while elderly patients (≥60 years) were more likely to develop ARF (65.22% vs 24.19%) (8). A further immunohistochemistry analysis revealed that the antigen for 2019-nCoV accumulates in renal tubules (8).…”