Healthcare providers have been hampered in their attempts to manage patients with COVID-19 in part because of an absence of reliable data on effective treatments, presenting characteristics, and clinical course of the disease. They have had to rely on the best information available, which in many instances comes from case series and single-institution experiences. Medical organizations have produced webinars featuring physicians relating how the pandemic has affected their institutions and the measures that staff took to control the spread of COVID-19.
The medical literature on COVID-19, however, has expanded quickly since the first report of the disease emerged from Wuhan, China, in December 2019, with accumulating research providing new information about the risk factors for infection with SARS-CoV-2, the novel coronavirus that causes COVID-19, as well as patient and clinical factors that predict outcomes.
A search of PubMed using the terms “COVID-19” or “SARS-CoV-2” on April 23 turned up more than 5900 reports. One of the latest studies was published online April 22 in the Journal of the American Medical Association. Investigators reported on a case series of 5700 patients with COVID-19 admitted to 12 Northwell Health system hospitals in the New York City area. The study included all sequentially hospitalized patients from March 1 to April 4.
Of the 5700 patients, 60.3% were male and 39.7% were female. Patients had a median age of 63 years. The most common comorbidities were hypertension, obesity, and diabetes, which were present in 56.6%, 41.7%, and 33.8% of patients. At triage, 30.7% of patients were febrile, 27.8% received supplemental oxygen, and 17.3% had a respiratory rate greater than 24 breaths/minute.
The investigators, led by Karina W. Davidson, PhD, of Northwell Health in New York City, assessed outcomes for 2634 patients who were discharged or had died at the study end point. During hospitalization, 21% died, 14.2% received treatment in an intensive care unit, 12.2% received invasive mechanical ventilation, and 3.2% received renal replacement therapy.
“To our knowledge,” the authors wrote, “this study represents the first large case series of sequentially hospitalized patients with confirmed COVID-19 in the US. Older persons, men, and those with pre-existing hypertension and/or diabetes were highly prevalent in this case series and the pattern was similar to data reported from China.”
Impact of renal impairment
Recently published studies also provide information about the impact of renal impairment on COVID-19 outcomes. For example, in a meta-analysis of studies examining the effect of chronic kidney disease (CKD) on COVID-19 severity, pooled data showed that patients with CKD had significant 3-fold greater odds of severe COVID-19, according to findings published in International Urology and Nephrology. The meta-analysis included 4 studies with a total of 1389 COVID-19 patients, of whom 273 (19.7%) were classified as having severe disease. Each study by itself did not find a significant association between CKD and COVID-19 severity.
“Based on a contrite meta-analysis of early and preliminarily available data, CKD seems to be associated with enhanced risk of severe COVID-19 infection,” wrote Brandon Michael Henry, MD, of The Heart Institute, Cincinnati Children’s Hospital Medical Center, and Giuseppe Lippi, MD, of University of Verona in Italy. “Patients with CKD should hence be advised to take extra precaution to minimize risk exposure to the virus.”
AKI in a Chinese hospital
In addition, a prospective cohort study of 701 patients hospitalized with COVID-19 in Wuhan, China, found that kidney disease on admission and development of acute kidney injury (AKI) during hospitalization independently predicted an increased risk for in-hospital death. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria, investigators at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported online in Kidney International. During the study period, AKI developed in 5.1% of patients. Elevated serum creatinine at baseline was significantly associated with 2.1-fold increased risk for in-hospital death, after adjusting for sex, age, disease severity, comorbidities, and leukocyte counts. Elevated blood urea nitrogen at baseline was significantly associated with a nearly 4-fold increased risk of in-hospital death. AKI stage 1, 2, and 3 were significantly associated with approximately 1.9-, 3.5- and 4.4-fold increased risks for in-hospital death.
In an article published online April 7 in the American Journal of Kidney Diseases, Ragu Durvasula, MD, MHA, and colleagues at Northwest Kidney Centers in Seattle related how their organization addressed COVID-19 after 2 patients dialyzing at their facilities died from the disease. Among another measures, staff implemented contact-droplet precautions and universal screening protocols across the organization’s 19 dialysis facilities. “A guiding principle from the outset was to keep stable ESRD patients out of the acute care setting, so as to not further burden our hospital partners,” they wrote.
The organization assessed its current continuous renal replacement therapy (CRRT) capacity and trended utilization patterns over the course of the COVID-19 outbreak, Dr Durvasula’s team stated. “While we still have sufficient capacity currently, the situation could spiral quickly. Given the diminished clinical impact of COVID-19 in the pediatric population, both in terms of volume and severity, we are speaking with colleagues at Children’s Hospital to potentially borrow additional CRRT machines should the clinical demand arise.”
In addition, Northwest Kidney Centers “engaged with local healthcare systems to assess resource availability and trend inpatient COVID-19 census, in order to better address evolving needs for renal replacement therapy at a regional level.”
Another report provides details of how physicians in Italy managed 46 patients with kidney disease at a hospital in Brescia (as of March 22). The patients included 21 on hemodialysis (HD), 20 kidney transplant recipients, and 5 with CKD. In a paper published in Kidney International Reports, they reported that 17 of the HD patients, 19 of the transplant recipients, and 4 of the 5 patients with CKD received antiviral therapy and hydroxychloroquine as part of a protocol established in their nephrology unit. Preliminary data show that as of March 22, 5 of the HD patients, 5 of the transplant recipients, and 2 of the CKD patients died, Federico Alberici, MD, of the University of Brescia, and colleagues reported.
The protocol the physicians followed uses a 2-phase approach. The first phase addresses viral replication and cytopathic effect. Clinicians may consider the use of antiviral drugs such as hydroxychloroquine or lopinavir-ritonavir, according to the authors. The second phase begins 7 to 10 days from the onset of symptoms. This stage is characterized by progressive lung involvement with escalating needs for oxygen supplementation and ventilator support, which appears to be secondary to hyperinflammatory and cytokine release syndromes. “Immunosuppressive and immunomodulatory drugs may be of benefit during this phase.”
Patients with known COVID-19 receive a chest X-ray at baseline, the authors noted. Additional chest X-rays are ordered when respiratory deterioration occurs. Even afebrile patients may have an abnormal chest X-ray and other clinical signs of hemophagocytic syndrome, they wrote. “These patients tend to be hypercoagulable, and prophylactic therapy with heparin and low-dose aspirin should be considered. During this phase, treatment with glucocorticoid and the interleukin-6 inhibitor tocilizumab should be considered, especially in patients with rapid clinical deterioration evidenced by escalating oxygen requirements or the need for ventilatory support,” the authors wrote.
Dr Alberici and his colleagues proposed a therapeutic management plan for HD and kidney transplant patients with COVID-19.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area [published online April 22, 2020]. JAMA. doi:10.1001/jama.2020.6775
Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection [published online March 28, 2020]. Int Urol Nephrol. doi: 10.1007/s11255-020-02451-9
Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19 [published online March 20, 2020]. Kidney Int. doi: 10.1016/j.kint.2020.03.005
Durvasula R, Wellington T, McNamara E, et al. COVID-19 and kidney failure in the acute care setting: Our experience in Seattle [published online April 7, 2020]. Am J Kidney Dis. doi: 10.1053/j.ajkd.2020.04.001
Alberici F, Delbarba E, Manenti C, et al. Management of patients on dialysis and with kidney transplantation during the SARS-CoV-2 (COVID-19) pandemic in Brescia, Italy [published online April 4, 2020]. Kidney Int Rep. doi: 10.1016/j.ekir.2020.04.001