COVID-19 in NYC: CV Risk Factors and Bleak Outcomes in the Critically Ill

New prospective evidence from the United States confirms a preponderance of cardiometabolic risk factors, a high incidence of critical illness among ethnic minorities, and bleak outcomes for the sickest COVID-19 patients.

Of 257 COVID-19 patients who became critically ill with acute hypoxemic respiratory failure at two New York City hospitals, one in northern Manhattan and the other in the Bronx, 101 had died and 94 remained in the hospital as of April 28, 2020. Nearly 80% of these patients required mechanical ventilation, which is higher than what was reported in observational studies from China and Washington state but in line with data from Italy, say investigators.

Consistent with other reports, investigators also showed that markers of inflammation and thromboembolism were both associated with higher risks of death, as were a number of key cardiometabolic risk factors in this critically ill population. 

“The results are what we’ve been seeing for the past 2 months here,” senior investigator Max O’Donnell, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), told TCTMD. “In a sense, it’s not surprising because we’ve been taking care of these patients and we’ve seen a lot of it. If you asked any of us 3 months ago, would you expect to see this degree of renal failure with a viral pneumonia, nobody would have expected to have a third of patients needing to go on dialysis, or expect the degree to which the inflammatory and thrombotic markers predict mortality. It’s all a little bit striking.”

One-Third of Patients Develop Severe Kidney Injury

In the study, published online May 19, 2020, in the Lancet, lead investigator Matthew Cummings, MD (NewYork-Presbyterian/Columbia University Irving Medical Center), and colleagues report on 1,150 adults with laboratory-confirmed COVID-19 admitted to Milstein and Allen Hospitals, both of which are part of the NewYork-Presbyterian hospital system, between March 2 and April 1, 2020.

Of the critically ill patients, 67% were men and the median age was 62 years. Roughly 42% of patients were younger than 60 years, including 19, 28, and 52 patients ages 30-39, 40-49, and 50-59 years, respectively. The vast majority of patients were either Hispanic/Latino (62%) or African-American/black (19%). The mean body mass index was 30.8 kg/m², with 68 and 33 patients with a BMI ≥ 35 and ≥ 40 kg/m², respectively. Most patients (82%) had at least one chronic illness. For example, nearly two-thirds of critically ill patients had hypertension and one-third had diabetes. Excluding high blood pressure, 19% of patients had a chronic cardiac condition. In total, 5% of patients were employed as a healthcare worker.  

It seems pretty clear that thrombosis is an incredibly strong feature of the disease. Max O’Donnell

After a minimum 28 days follow-up, 39% of critically ill patients had died following a median of 9 days in the hospital. Of the 203 patients who received mechanical ventilation, 84 had died. By race and ethnicity, 41%, 38%, and 47% of African-American/black, Hispanic/Latino, and white patients died, respectively. Most deaths occurred in those 50 years and older.

In this analysis, the 94 surviving patients had been hospitalized a median of 33 days. Only 23% of the critically ill patients were discharged. For those discharged, 21% needed supplemental oxygen and 2% were transferred to another facility.

In terms of patient management, 66% of patients received vasopressors and 31% developed severe kidney injury requiring renal replacement therapy, such as dialysis. Antibacterial agents were given to nearly all patients, while 72% also received hydroxychloroquine and 9% received remdesivir (Gilead Sciences) through enrollment in clinical trials or compassionate-use access. One-quarter received corticosteroids and 17% received interleukin (IL)-6 receptor antagonists at the discretion of treating physicians in consultation with infectious disease experts.   

In a multivariable model, older age, chronic cardiac disease, chronic pulmonary disease, higher concentrations of IL-6, and higher concentrations of D-dimer were all independently associated with a higher risk of in-hospital mortality.

“This is consistent with what we’ve been seeing,” said O’Donnell. “It seems pretty clear that thrombosis is an incredibly strong feature of the disease.”

Giacomo Grasselli, MD, and Alberto Zanella, MD (both from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy), who wrote an editorial accompanying the study, say the new prospective data confirm that COVID-19 is characterized by a high incidence of multiple organ dysfunction, as shown by the high incidence of vasopressors and renal replacement therapy.

They add that the link between higher concentrations of IL-6 and D-dimer is particularly important.

“First, it confirms the key pathogenic role played by the activation of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction,” write Grasselli and Zanella. “Second, it provides the rationale for the design of clinical trials for measuring the efficacy of treatment with immunomodulating and anticoagulant drugs.”

O’Donnell said that at this point there will be a need for more high-quality evidence to develop guidelines to drive the care of critically ill patients with COVID-19. So far, the antiviral agent remdesivir has been shown to be of modest benefit in a single randomized controlled trial; other agents are in testing. Use of anticoagulation to prevent thromboembolism also needs further study, and trials are ongoing, although some centers have adopted a strategy of giving anticoagulants for COVID-19 patients, depending on their risk of bleeding.  

Happy Hypoxia Not Evident

To TCTMD, O’Donnell noted that they didn’t observe patients with “silent” or “happy” hypoxia, which occurs when oxygen levels fall but the patient doesn’t experience shortness of breath, a phenomenon that has been reported in other observational studies and in the media. In the present analysis, 74% of the critically ill patients reported shortness of breath, 71% had a fever, and 66% had a cough. 

“These patients obviously become extraordinarily sick,” said O’Donnell, referring to COVID-19 patients treated in the ICU. “A lot of the issues that we care about in ‘happy’ hypoxia, meaning patients with very hypoxic, very low oxygen levels but very compliant lungs, that wasn’t seen in our center. A lot of what we hear by anecdote is that these patients are very different physiologically from other patients with severe respiratory failure, but what we saw is that these are folks with very low oxygen levels and very stiff lungs like we’ve seen in other large cohorts.”

For O’Donnell, the new study is also important because it shows that high-quality evidence can be collected and published even during an epidemic. “When things are tough, and you have low-quality data, you can actually go pretty far down the wrong road and that can be pretty harmful,” he said. “To me, this is one of the messages. When the second wave comes, we need to marshal our evidence base and do things that we know help patients.”