Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient

Abstract

In this study, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins and virus particles can be detected (i) in post-mortem kidney of fatal coronavirus disease 2019 (COVID-19) patients and (ii) in renal biopsy of patients suffering from kidney failure months after combating a SARS-CoV-2 infection. Using fluorescence microscopy, antibodies against viral proteins [nucleocapsid, membrane (M), non-structural proteins (nsp) 3, 4, and 13] and double-stranded RNA (dsRNA) were validated on SARS-CoV-2-infected Vero cells. dsRNA was detected in lipid-filled electron-lucent (white) compartments in SARS-CoV-2-producing cells. In the kidney of a patient with acute kidney failure, accumulation of SARS-CoV-2 nucleocapsid N protein was detected in tubular epithelium. In contrast, none of the other viral proteins (M, nsp3, 4, 13) nor dsRNA was detected in these regions, suggesting that no viral replication takes place in the kidney of these patients. High-resolution immunoelectron microscopy demonstrated N protein accumulation in Golgi-like structures but absence of intracellular virus particles. The presence of the N protein in Golgi-like structures in kidney of patients suggests that this protein may have an unforeseen role in post-COVID-19 renal complications. IMPORTANCE Even though the coronavirus disease 2019 (COVID-19) pandemic is slowly developing into a conventional infectious disease, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection are still not well understood. One of the problems is that many COVID-19 cases develop acute kidney injuries. Still, it is heavily debated whether SARS-CoV-2 virus enters and actively replicates in kidney tissue and if SARS-CoV-2 virus particles can be detected in kidney during or post-infection. Here, we demonstrated that nucleocapsid N protein was detected in kidney tubular epithelium of patients that already recovered form COVID-19. The presence of the abundantly produced N protein without signs of viral replication could have implications for the recurrence of kidney disease and have a continuing effect on the immune system.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…Another aspect of canonical inflammation in LC, which was not included in the aims and objectives of our study, is considering LC as a risk factor for the onset of various inflammatory diseases or the progression of existing inflammatory diseases [ 323 , 324 , 325 , 326 , 327 ]. This primarily concerns immune-dependent diseases, whose association has been established, namely various allergic, autoimmune, and infectious diseases, but also should be taken into account in other pathological conditions as well [ 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 ,…”

“…It has been observed that the N protein of SARS-CoV-2 persists in the renal tubule epithelium of recovered COVID-19 patients. The presence of the N protein, even without signs of viral replication, may be significant for the recurrence of kidney disease and have lasting effects on the immune system [ 279 ].…”

The Role of Extracellular Vesicles in SARS-CoV-2-Induced Acute Kidney Injury: An Overview

“…In addition, more studies have demonstrated the presence of SARS-CoV-2 N protein accumulations in the kidney tubular epithelium of patients with COVID-19 [91,[109][110][111]. Another immunoelectron microscopy study revealed the accumulations of SARS-CoV-2 N protein in one patient previously diagnosed with COVID-19 three months prior to the manifestation of kidney failure [112]. Thus, the urinary SARS-CoV-2 N protein may serve as an indicator of the likelihood of AKI development, which may provide clinicians with insights into the severity of COVID-19 [113].…”