Patients with SARS-CoV presented with ischemic stroke, likely due to the hypercoagulable state and vasculitis induced during the illness110 (Table 5 ). Case reports mentioned the detection of SARS-CoV in the cerebral spinal fluid (CSF) of patients who subsequently developed seizures.111 , 112 Tsai et al studied 4 patients with SARS-CoV who developed neuropathy and myopathy. Since they did not find CSF evidence of viral invasion, they attributed these findings to critical illness polyneuropathy and myopathy.113
Table 5 Renal manifestations of SARS-CoV, MERS-CoV and COVID-19.
SARS (only studies with large study population included)
Study Booth et al (2003)N = 144, confirmed casesRetrospective study Choi et al (2003)N = 267 (227 confirmed cases)Retrospective study Zou et al (2004)N = 165, confirmed casesRetrospective study Chan et al (2004)N = 669, (323 tested positive)Clinicopathologic study Huang et al (2004)N = 78, probableRetrospective study Ding et al (2004)N = 8 (4 confirmed cases, 4 control)Clinicopathologic study Chu et al (2005)N = 536, confirmed casesRetrospective study
Clinical features Renal dysfunction ARF (6%) during course of hospitalization Renal dysfunction N/A ARF (17%). 7.2 ± 4.3 days after admission N/A ARF (6.7%) within 5-48 days of onset (median 20)
Key findings on investigations • ↑ Cr
• ↑ Urea
• ↓Ca++ (60%)
• ↓K+ (26%)
• ↓Mg++ (18%)
• ↓P+ (27%)
• ↑ LDH (87%) ↑ Cr ↑ Cr↑ Urea • Virus first detected in urine on day 7, stared to decline after day 16 ↑ Cr N/A Cr normal at presentation, then ↑
Histopathology N/A N/A N/A N/A N/A Virus detected in distal convoluted renal tubule Acute tubular necrosis, no evidence of glomerular pathology
Key study findings and message ↑ Urea > ↑ Cr associated with mortality (P = 0.003, P = 0.02) ↑ Cr associated with mortality (P < 0.001, univariate) ↑ Cr, ↑ Urea associated with poor prognosis (P = 0.001, P = 0.003) Virus can persist >30 days after symptom onset in urine • ARF more common in older age, males (P < 0.05), diabetics (P < 0.01), patients with heart failure (P < 0.001)
• Renal features may be due to pre-renal factors, hypotension, rhabdomyolysis, comorbidities including diabetes, age ACE2 expressed and virus detected in kidneys • ARF significant risk factor for mortality (P < 0.001) (uni and multivariate)
• ARF more likely in older age group, patients with ARDS, and requiring inotropes (P < 0.001)
• ↓albumin, ↑ ALT at presentation, ↑ peak CPK after admission associated with development of ARF (P < 0.001, P = 0.004,P < 0.001)
• Renal features likely multiorgan failure related, no direct viral pathology
MERS
Study Assiri et al (2013)N = 47, confirmed casesRetrospective study Arabi et al (2014)N = 12 (11 confirmed cases, 1probable)Case series Saad et al (2014)N = 70, confirmed casesRetrospective study Cha et al (2015)N = 30, confirmed casesRetrospective study Yeung et al (2016)Ex-vivo organ cultureNonhuman primate modelClinicopathologic Alsaad et al (2017)N = 1, confirmed casesClinicopathologic study
Clinical feature Coexisting chronic renal disease (49%) • Coexisting chronic renal disease (42%)
• ARF requiring RRT (58%) ARF (42.9%) • Coexisting chronic renal disease (10%)
• ARF (26.7%) N/A
Histopathology N/A N/A N/A N/A Smad7 and FGF2 expression elevated in kidneys of infected animals • Tubular epithelial cell degenerative and regenerative changes
• Mild glomerular ischemic changes
• Viral particles detected in proximal tubular epithelial cells
Key study findings and message Chronic renal disease was a common comorbidity Renal features may be due to:• Cytokine dysregulation
• Direct viral invasion
• Autoimmune Acute kidney injury is a common complication • AKI more likely in older patients (P = 0.016)
• Preexisting CKD not associated with later development of AKI
• AKI, RRT risk factors for mortality (univariate) MERS-CoV induced apoptosis via upregulation of Smad7 and FGF2 expression Tissue trophism in kidneys
COVID-19
Study Wang et al (2020)N = 138, confirmed casesRetrospective study Cheng et al (2020)N = 701, confirmed casesRetrospective study Wang et al (2020)N = 205, confirmed casesClinicopathologic Li et al (2020)N = 193, confirmed casesRetrospective study Zhou et al (2020)N = 191, confirmed casesRetrospective study
Clinical Features • Coexisting chronic renal disease (2.9%)
• AKI (3.6%) • Coexisting chronic renal disease (2%)
• AKI (3.2%) N/A • AKI (28%) • AKI (15%) (Av 15 days after symptom onset)
Key findings on investigations ↑ Cr • ↑ Cr (14.4%)
• ↑ Urea (13.1%)
• eGFR<60 (13.1%)
• Proteinuria (43.9%)
• Hematuria (26.7%) No viral detection in urine (72 samples) • ↑ Cr (10%)
• ↑ Urea (14.%)
• Proteinuria (59%)
• Hematuria (44%) ↑ Cr
Key study findings and message • ICU patients more likely to have ↑ Cr (P = 0.04), ↑ BUN (0.001)
• Cr and urea increased with disease progression • ↑ Cr at admission more common in males, older patients, more severe disease (P < 0.001, P < 0.001, P = 0.026)
• AKI, in hospital death, mechanical ventilation more common in patients with baseline ↑ Cr (P < 0.001, P < 0.001, P = 0.012)
• Higher in hospital death rate with proteinuria, hematuria, baseline ↑ Cr, Urea, AKI Stage 2 or 3 (P < 0.001; P = 0.003 for AKI stage 1)
• Renal features may be due to direct viral effect, immune mediated, virus induced cytokines and mediators. No viral shedding in urine AKI associated with severe outcome (P < 0.001) • ↑ Cr associated with in-hospital death
(P = 0.045)
• Higher incidence of AKI in nonsurvivors (P < 0.001)
ACE2, Angiotensin-converting enzyme 2; AKI, acute kidney injury; ARF, acute renal failure; BUN, blood urea nitrogen; CKD, chronic kidney disease; CPK, creatine phosphokinase; Cr, creatinine; eGFR, estimated glomerular filtration rate; LDH, lactate dehydrogenase; MERS-CoV, middle east respiratory syndrome coronavirus; SARS-COV, severe acute respiratory syndrome coronavirus; RRT, rapid response team.