It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.

Anemia commonly aggravates the severity of respiratory diseases, whereas thus far, few studies have elucidated the impact of anemia on coronavirus disease 2019 (COVID‐19). The aim of this study was to evaluate the clinical characteristics of patients with anemia, and to further explore the relationship between anemia and the severity of COVID‐19. In this single‐center, retrospective, observational study, a total of 222 confirmed patients admitted to Wuhan Ninth Hospital from 1 December 2019 to 20 March 2020 were recruited, including 79 patients with anemia and 143 patients without anemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID‐19 were established by univariable and multivariable logistic regression models. In our cohort, compared to patients without anemia, patients with anemia were more likely to have one or more comorbidities and severe COVID‐19 illness. More patients demonstrated elevated levels of C‐reactive protein (CRP), procalcitonin (PCT) and creatinine in anemia group. Levels of erythrocyte sedimentation rate, D‐dimer, myoglobin, T‐pro brain natriuretic peptide (T‐pro‐BNP) and urea nitrogen in patients with anemia were significantly higher than those without. In addition, the proportion of patients with dyspnea, elevated CRP, and PCT was positively associated with the severity of anemia. The odd ratio of anemia related to the severe condition of COVID‐19 was 3.47 (95% confidence interval [CI]: 1.02‐11.75; P = .046) and 3.77 (95% CI: 1.33‐10.71; P = .013) after adjustment for baseline date and laboratory indices, respectively. Anemia is an independent risk factor associated with the severe illness of COVID‐19, and healthcare professionals should be more sensitive to the hemoglobin levels of COVID‐19 patients on admission. Awareness of anemia as a risk factor for COVID‐19 was of great significance.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP⁺ macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

Sustained activation of autophagy and lipid accumulation in tubular epithelial cells (TECs) are both associated with the kidney fibrosis progression. Autophagy has been found involved in the lipid metabolism regulation through a bi-directional mechanism of inducing lipolysis as well as promoting lipid droplet formation. However, whether and how autophagy influences lipid accumulation in kidney fibrosis remain unclear. In the current study, we show that UUO-induced lipid accumulation in tubular cells was significantly reduced when the pharmacological inhibitor 3-MA or CQ was administrated both in vivo and in vitro. Of interest, colocalization of LDs and autophagosomes, as well as colocalization of LDs and lysosomes were undetected in UUO-induced fibrotic kidneys, although lysosome function remained robust, indicating the lipid accumulation is lipophagy-lysosome pathway independent. TGF-β1-induced lipid droplets formation in HK-2 cells were decreased when the Beclin-1 expression was silenced, implying that autophagy-upregulated lipid droplets formation is Beclin-1 dependent. Finally, CQ treatment of UUO-induced fibrotic kidneys reduced the expression of α-SMA and tubular cell apoptosis and rescued the expression of E-cadherin, which was associated with the ameliorated lipid deposition. Therefore, our work documented that autophagy promotes lipid droplet formation in TECs in a Beclin-1-dependent manner, which causes renal lipotoxicity and contributes to the progression of kidney fibrosis.

The outbreak of highly contagious coronavirus disease 2019 (COVID-19) has posed a serious threat to human life and health, especially for those with underlying diseases. However, the impact of COVID-19 epidemic on hemodialysis (HD) centers and HD patients has not been reported. We reviewed the whole course of the COVID-19 in the HD center of Renmin Hospital, Wuhan University (from January 14, 2020, to March 12, 2020). We compared the clinical manifestation and immune profiles among different patient groups with healthy individuals. Forty-two of 230 HD patients (18.26%) and 4 of 33 medical staff (12.12%) were diagnosed with COVID-19 during the study period. Fifteen HD patients (6.52%), including 10 COVID-19 diagnosed, died. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure, others were ascribed to cardiovascular/cerebrovascular diseases or hyperkalemia. Except for 3 patients who were admitted to the intensive care unit for a severe condition (8.11%), including 2 who died, most COVID-19 diagnosed patients presented mild or nonrespiratory symptoms. The flow cytometric analysis of peripheral blood showed that multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other patients with COVID-19. Compared with the general population, HD patients and health care professionals are the highly susceptible population and HD centers are high-risk areas during the outbreak. Most HD patients with COVID-19 exhibited mild clinical symptoms and did not progress to severe pneumonia, likely due to the impaired cellular immune function and incapability of mounting cytokine storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of the COVID-19 epidemic on HD patients.