April 7, 2020

SARS-CoV-2 detected in blood donations, kidney disease linked to in-hospital death in patients with COVID-19, and characteristics and outcomes of 1,591 patients admitted to ICUs in Lombardy

By Denise Baez

NEW YORK -- April 7, 2020 -- Today’s DG Alert covers the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood donations, the effect of kidney disease on in-hospital mortality in patients with coronavirus disease 2019 (COVID-19), and the characteristics and outcomes of 1,591 patients with COVID-19 admitted to intensive care units (ICUs) across the Lombardy Region in Italy. 

SARS-CoV-2 RNA was found in plasma during routine screening of healthy blood donors in Wuhan, China, according to a study published in Emerging Infectious Diseases.

Most blood centres and blood banks in China began taking measures to ensure blood safety following the rapid increase in COVID-19 cases in Wuhan. Wuhan Blood Center began screening for SARS-CoV-2 RNA on January 25, 2020. 

“We screened donations in real-time and retrospectively, and found plasma samples positive for viral RNA from 4 asymptomatic donors,” reported Le Chang, MD, National Center for Clinical Laboratories, Beijing Hospital, Beijing, China, and colleagues. “Samples from these donors were further tested for specific IgG and IgM against SARS-CoV-2 by ELISA [enzyme-linked immunosorbent assay]; results were negative, indicating the possibility of infection in the early stage and the need to follow-up with these donors.”

Dr. Chang and colleagues screened a total of 2,430 donations (1,656 platelet and 774 whole blood donations) in real time. The first positive donor was identified and showed a weak positive result near the limit of detection. A throat swab specimen collected from the donor on February 10 was positive. The donor reported no symptoms and was quarantined until February 25.

Retrospective testing of 4,995 donations collected from December 21, 2019 to January 22, 2020, was collected by using retained nucleic acid template after routine pool testing. On February 10, the researchers found a positive result in a nucleic acid template derived from donations collected on January 19. They then individually tested samples that were in storage at 2 to 8 degrees Celsius for 23 days. Another positive donor of whole blood was identified. Plasma products from this donation were tested twice and noted similar results, which suggests that viral RNA is relatively stable in plasma. None of the blood products produced from the donor had been used. Telephone follow-ups on February 15 and 25 showed that this donor remained asymptomatic and quarantined at home.

In telephone follow-ups with donors who gave blood during January and February, 33 donors developed a fever after donation and all of their donations were removed from circulation. The researchers performed retrospective individual screening on frozen plasma products from 17 donors and tested the retained nucleic acid templates after routine pool testing of the other 16 donors -- 2 more positive donors who donated whole blood on January 20 were found. Both had weak positive results, and donors reported fever onset on January 21. Donor 3 treated patients infected with SARS-CoV-2 in a Wuhan hospital. His temperature returned to normal 8 days after donation. Donor 4’s temperature also returned to normal 7 days after taking self-prescribed antipyretic medications.

“One limitation of our study is that we did not have more detailed information on donors 2, 3, and 4,” the authors wrote. “Although we could not confirm virions in blood or whether the virus could be transmitted in blood products, the potential risk should not be neglected. However, detectable RNA might not signify infectivity. Further studies, such as virus culture, should be done to explore the possibility of viremia and follow-up of donors also is essential.”

Another study, published in Kidney International, showed that patients with COVID-19 with kidney disease on admission had higher in-hospital mortality, as did patients who developed acute kidney injury (AKI) during hospitalisation. 

The study included 701 patients aged 50 to 71 years admitted with COVID-19 in Wuhan, China, of whom 113 (16.1%) died in hospital. 

“In this large prospective cohort study conducted in a tertiary teaching hospital with 3 branches in Wuhan, China, we observed a high prevalence of kidney disease in hospitalised patients with COVID-19,” wrote Shuwang Ge, MD, Tongji Hospital, Wuhan, and colleagues. “More than 40% of them had evidence of kidney disease, with elevated serum creatinine and BUN values in over 13% of them. Strikingly, the presence of kidney disease was associated with greater in-hospital mortality. 

On admission, 43.9% of the patients had proteinuria and 26.7% had haematuria. The prevalence of elevated serum creatinine was 14.4%, elevated blood urea nitrogen was seen in 13.1%, and estimated glomerular filtration <60 ml/min/1.73m2 was seen in 13.1%. During hospitalisation, AKI occurred in 5.1%. 

Independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity, and leukocyte count included elevated baseline serum creatinine (hazard ratio [HR] = 2.10, 95% confidence interval [CI], 1.36-3.26), elevated baseline blood urea nitrogen (HR = 3.97; 95% CI, 2.57-6.14), AKI stage 1 (HR = 1.90; 95% CI, 0.76-4.76), AKI stage 2 (HR = 3.51; 95% CI, 1.49-8.26), AKI stage 3 (HR = 4.38; 95% CI, 2.31-8.31), proteinuria (HR = 1.80-4.84, depending on severity) and haematuria 1D (HR = 2.99-5.56, depending on severity).

“This is the first study showing an association between kidney involvement and poor outcome in patients with COVID-19,” the authors wrote. “We found that patients with elevated baseline serum creatinine were more likely to be admitted to the intensive care unit and to undergo mechanical ventilation, suggesting that kidney disease on admission represented a higher risk of deterioration. Monitoring kidney function must therefore be emphasised even in patients with mild respiratory symptoms, and altered kidney function should be given particular attention after admission in clinical practice. Early detection and treatment of renal abnormalities, including adequate hemodynamic support and avoidance of nephrotoxic drugs, may help to improve the vital prognosis of COVID-19.”

Lastly, a case series published in JAMA describes the outcomes of 1,591 critically ill patients admitted with COVID-19 from February 20, 2020, to March 18, 2020, to 1 of 72 hospitals in the Lombardy region of Italy. 

“In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP [positive end-expiratory pressure], and ICU mortality was 26%,” reported Giacomo Grasselli, MD, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, and colleagues. 

Patients were aged 56 to 70 years and 82% were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity, the most common being hypertension (49%), followed by cardiovascular disorders, hypercholesterolemia, and diabetes. Among 1,300 patients with available respiratory support data, 1,287 (99%) needed respiratory support. The majority of patients in this case series were admitted to the ICU because of acute hypoxemic respiratory failure that required respiratory support. Endotracheal intubation and invasive mechanical ventilation were needed in 88% of the patients, whereas only 11% could be managed with non-invasive ventilation. 

The authors said that the higher rate of intubation in the current case series could be due to the severity of hypoxia. 

“In this study, at 5 weeks after the first admission in ICU, the majority of the patients (58%) were still in the ICU, 16% of the patients had been discharged from the ICU, and 26% had died in the ICU,” the authors wrote. “The death rate was higher among those who were older. However, these outcome data should be interpreted with caution because most patients were still hospitalised in the ICU and the minimum follow-up was 7 days -- in particular, the mortality rate could eventually be higher.”

The authors noted several limitations, the first being the retrospective nature of the study, and the second being the inability to obtain more detailed information about patients (such as baseline medication use) due to the critical nature of the Lombardy situation. In addition, follow-up time is still relatively short and the reported mortality data and length of stay data reported could change.

SOURCE: Emerging Infectious Diseases, Kidney International, JAMA
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