Currently, three publications are available describing coronavirus outcomes among hospitalized patients in New York:
- Goyal et al: 393 patients at Cornell.
- Cummings et al: described 257 patients who were critically ill (among a total of 1,150 patients at Columbia and a community affiliate).
- Richardson et al: 5700 patients at Northwell Health System (including North Shore University Hospital, Long Island Jewish Medical Center, Lenox Hill, and several other hospitals).
This post will attempt to synthesize these publications, focusing on some clinically useful bits of information.
Epidemiology
- Men are affected more: About 60-65% of admitted patients were male. Men were also more likely to require intubation.
- Link to insulin resistance? The most common comorbidities seem to cluster with metabolic syndrome (diabetes, morbid obesity, hypertension, and male sex).
Presenting symptoms
- Fever is often absent. Objective fever at initial presentation occurred at a rate of 31% in Northwell Health and 25% at Cornell. This is considerably lower than in previous series. The reason for this is unclear (numerous possible explanations exist, including: differences in temperature measurement technique, different temperature cutoffs, delayed presentation to medical attention).
- Initial gastrointestinal symptoms: The Cornell series reported that 24% of patients presented with diarrhea and 19% presented with nausea or vomiting. This is considerably higher than in prior series.
Clinical course
- Delayed presentation: Patients often present after about a week of clinical illness (Columbia reported a median of six days). This may coincide with the initiation of an adaptive immune response to the virus.
- Initially normoxemic patients who later crash: At Cornell, 31% of patients required no supplemental oxygen initially, yet subsequently deteriorated leading to intubation. Likewise, the Columbia series described a median of 3 days (interquartile range 1-6) between hospital admission and clinical deterioration.
Presenting labs
- A respiratory virus co-infection rate of 2% was found at Northwell and 1% at Cornell. This is lower than reported in some previous studies. This rate may be decreasing over time, as winter passes and the rate of various non-COVID viruses wane. By summer, this co-infection rate may fall below 1%.
- Performance of lymphopenia? At Northwell, only 60% of patients had absolute lymphopenia (an absolute lymphocyte count <1000 billion/L). Alternatively, the Cornell series found that 90% of patients had a lymphocyte count below 1500 billion/L. Thus, when screening for COVID-19, it may be reasonable to consider using a cutoff of <1,500 billion/L lymphocytes (although admittedly, further information is required on the specificity of this cutoff).
Presenting imaging
- At Cornell, the initial chest radiograph was clear in 17% of patients, showed unilateral infiltrate in 16%, showed bilateral infiltrates in 60%, and showed a pleural effusion in 6%.
- The rate of infiltrates is much higher among critically ill patients. In the Columbia series, infiltrates were present on 98% of chest X-rays at the time of admission.
- Thus, clinical context needs to be integrated with chest radiograph. For a critically hypoxemic patient, a clear chest X-ray would argue against COVID-19 as the cause of the patient’s hypoxemia. Alternatively, for a slightly ill patient, a clear chest X-ray could be entirely compatible with COVID-19 as the cause of the patient’s flu-like syndrome.
Respiratory management
- A strategy of early intubation seems to have predominated at all locations during the period of investigation. For example, in the Columbia series high flow nasal cannula was used in 5% of patients and noninvasive ventilation in 1% of patients, compared to invasive mechanical ventilation in 79% of patients. Cornell likewise described a strategy of early intubation.
- The Columbia series provided more granular detail regarding mechanical ventilation. The median length of intubation among survivors was 14 days (with an interquartile range of 12-18 days). The highest PEEP over the first 24 hours was a median of 15 cm. 25% of intubated patients were treated with early neuromuscular blockade, 11% with inhaled nitric oxide, 16% with prone ventilation, and 2% with ECMO.
Medical therapy
- The Cornell series reported the use of hydroxychloroquine in 64% of patients, remdesivir in 4% of patients, and oral steroid in 12% of patients.
- The Columbia series reported that 72% of patients received hydroxychloroquine and 9% recieved remdesivir. 26% were treated with corticosteroid and 23% with IL-6 receptor antagonists. Higher use of anti-inflammatory agents likely reflects that all patients in this series were critically ill.
Acute kidney injury and renal replacement therapy
- This is a common problem which is associated with very high morbidity.
- In the Northwell Health series, 3% of patients required dialysis (compared to 14% admitted to the intensive care unit). Among 81 patients who received dialysis, only three were discharged alive.
- In the Cornell series, 5% of patients required initiation of dialysis. 17 of 18 patients who required dialysis initiation were among the cohort of patients who were intubated.
- In the Columbia series, 29% of critically ill patients received dialysis. 87% of patients in this series had proteinuria.
Cardiac failure
- This didn’t seem to be a major issue.
- Within the Cornell series, only 7/393 patients developed heart failure. Only one patient developed a ventricular arrhythmia. No patient received mechanical cardiac support. Most patients who were intubated did require vasopressor (95%) but the significance of this is unclear (e.g. this may have been transient or utilized to counteract the effect of vasodilating sedative agents).
Mortality of intubated versus non-intubated patients
- Deaths seemed to accrue over a time-frame of at least a month (figure below from Columbia series). Thus, studies lacking adequate follow-up will under-estimate mortality.
- Outcomes of intubated patients are shown below, with a comparison to a large series from Italy (Grasseli et al.).
- Lack of long-term followup data makes it impossible to determine the actual mortality of these patients. However, it's probably fair to say that mortality and morbidity are high among intubated patients. This is particularly notable given two additional considerations:
- (1) Many patients were reasonably healthy prior to becoming ill.
- (2) There was generally a lower threshold for intubating COVID-19 patients, so this cohort of patients may have initially had less severe respiratory failure (compared to a non-COVID cohort of patients intubated due to respiratory failure).
- Outcomes were dramatically better for patients who weren't intubated (for example, at Cornell 90% of patients who weren't intubated were discharged from the hospital).
- Hypertension was a strong correlate of mortality. At Columbia, 50% of critically ill patients with a history of hypertension died (figure below).
- Mortality increased with age, but a substantial number of relatively young patients also died. Data below from critically ill patients at Columbia:
Prognostic factors
- With the Columbia series independent predictors for mortality were age, history of chronic lung disease, elevated IL-6, and elevated D-dimer (table below)
- Fever had a low sensitivity for COVID in these series (~25-30%). This casts some shade on the practice of checking employees’ temperature upon reporting to work (which is often performed hastily and with dubious technique). A better approach might to focus more on various symptoms.
- A considerable group of patients initially have normal oxygen saturation, but subsequently deteriorate and are intubated. Prediction of disease course based on vital signs will often fail.
- Survival in COVID-19 is closely tied to pulmonary and renal function, whereas cardiac failure appears less prominent.
- Outcomes for intubated patients were poor across all institutions. This might result partially from the disease surge causing services to be over-stretched, challenging the ability to personalize ventilator settings and sedation. It is also possible that in some cases intubation could precipitate ventilator-induced lung injury and hemodynamic shifts leading to multi-organ failure. Overall, this data may argue for use of noninvasive respiratory support, with avoidance of intubation if possible.
Image credit: Photo by Luca Bravo on Unsplash
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Great summary! Any new insights on coagulation/thrombosis?
The data is also consistent with the sicker patients, who have the worst affected lungs, being the most likely to die.
Early intubation may not be necessary but survivors are likely being selected by being those people that don’t get sick enough to require invasive ventilation.
That is exactly right. You cannot make any statement about the effect of intubation by interpreting these discriptive data. The only way to know for sure would be to randomize equally sick patients to early and late intubation.
By only looking at mortality rates of ALL patients who were intubated you create a huge bias towards sicker patients.
For the record: I am an “HFO/CPAP for COVID”- advocate myself and had to explain myself a lot for not intubating every COVID-19 patient at my ICU…
Thanks for the excellent summary . Your blog’s have been really helpful for me and my colleagues back here in Ethiopia .
Great summary, thanks! We have moved away from early intubation in the last 2 weeks and using HFNC with good results. (Some will progress and fail later, of course) . We haven’t seen LV dysfunction and myocarditis, some RV dysfunction that is expected in ARDS and with mechanical ventilation. Our deaths tend to be weeks later, so that certainly resonates,, mostly PEA w/o clear LV or RV dysfunction. Some require tracheostomies (day 10-20)..
Pedro Salinas
Thank you for the summary. In my trust we moved away from early intubation quite early during the surge, and started to put patients on CPAP on the wards, with maximum of PEEP 10 and FIO2 60%. This seems to have paid off, since we were to avoid intubation in a substatational number, and a big percent got better just by CPAP. We would have used HFNO, but were concerned about oxygen supply. Patients whom were on CPAP for a long time and need intubation seem to follow under the H ARDS like phenotype. Recently we decided to uncouple PEEP… Read more »
What doses of steroid did you use on the regular ward?
I do not agree with your conclusions regarding intubation. It should be that patients who require mechanical ventilation are sicker and have a higher mortality. The mortality for patients who require mechanical ventilation is unclear from these studies: the majority of the patients on mechanical ventilation were still in the hospital (and presumably alive) at the end of the study. As you point out correctly, we would need to look at ICU, hospital, 30 and 60 day mortality, but that has not been done so the information can get out quickly. These patients have long duration of mechanical ventilation after… Read more »
Delaying intubation as long as possible is common practice for respiratory failure as far as I know. Mechanical intubation is avoided for myriad reasons, among them VAP and progressive weakness. One reason I can see to avoid early intubation is that in order to avoid aerosolizing procedures these patients are not progressed to tracheostomy and remain intubated for up to 4 weeks and some even longer. I don’t think Josh is suggesting withholding intubation altogether for anyone.
You might want to do labs on your COVID-19 patients for 25(OH)D3. I suspect nearly all of them are vitamin D3 deficient with a mean 25(OH)D3 around 12 to 15 ng/mL or less for the more critical. The 25(OH)D3 response to dose for most adults is 10 ng/mL for every 100,000 IU of vitamin D3 taken. Accordingly, most will need a total vitamin D3 loading dose around 600,000 IU.. 200,000 IU/day vitamin D3 for 3 days should work just fine, Well tolerated and no harms. Here’s my data from 320 people prior to vitamin D3 repletion. [img[/img] 400 mg/day magnesium… Read more »
I’ve sent similar data to Paul Marik. The sot after physiological response to oral vitamin D3 at these doses is relatively rapid, 24-36 hours.
Hey Josh great post as usual. I wanted to let you know I work at NS and LIJ and we didn’t really have an early intubation strategy here when that data was collected. Our ICUs were overwhelmed and many patients were on the floors with tachypnea on both NC and NRB to keep sats >90% for several days before getting intubated. We were not using HFNC or NIV at all when this data was collected.
Thanks for everything you do I learn so much from your posts.