Covid-19 in Critically Ill Patients in the Seattle Region — Case Series

We included patients with laboratory-confirmed Covid-19 infection who were admitted to nine hospital ICUs in the Seattle region between February 24 and March 9, 2020. A confirmed case of Covid-19 was defined by a positive result on a reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay of a specimen collected on a nasopharyngeal swab. Only laboratory-confirmed cases were included.

Twenty-four adults (18 years of age or older) were identified from nine hospitals, including three University of Washington (UW) Medicine Hospitals (Harborview Medical Center, UW Medical Center–Montlake, and Northwest campuses), the Virginia Mason Medical Center, and the Swedish Hospitals (First Hill and Cherry Hill). This group represents six of the eight adult acute care hospitals in the city of Seattle; hospitals connected to these systems in suburbs outside Seattle (UW–Valley Medical Center, Swedish–Issaquah, and Swedish–Edmonds) were also included in the group of nine. Pregnant women, prisoners, and children (those younger than 18 years of age) were excluded from the study. The UW institutional review board approved this study with the reliance agreement (also known as an authorization agreement) of other local medical centers. The institutional review board at Swedish Medical Center also independently approved the study. Informed consent was waived, and researchers analyzed only deidentified (anonymized) data.

Data from each institution’s electronic medical record was obtained through a research form in Research Electronic Data Capture software (REDCap, Vanderbilt University). We obtained demographic data, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during ICU admission. All laboratory tests and radiologic assessments, including plain chest radiography and computed tomography of the chest, were performed at the discretion of the treating physician.

Coexisting conditions were ascertained from physician documentation. Patient data were censored at the time of data cutoff, which occurred on March 23, 2020. Acute respiratory distress syndrome (ARDS) was defined as acute-onset hypoxemia (the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen [Pao₂:Fio₂], <300) with bilateral pulmonary opacities on chest imaging that were not fully explained by congestive heart failure or other forms of volume overload.¹⁰

Clinical specimens for Covid-19 diagnostic testing were obtained in accordance with Centers for Disease Control and Prevention (CDC) guidelines. Initially, all clinical specimens were tested with the assay developed by the CDC, targeting the N1 and N2 genes,¹¹ which was run at the Washington Department of Health State Public Health Laboratory. On March 2, UW began using an assay developed by the UW School of Medicine clinical virology laboratory (see the Methods section in the Supplementary Appendix, available with the full text of this article at NEJM.org). The assay is based on the World Health Organization standard, and it targets the SARS-CoV-2 E gene and RdRp gene.¹² If both targets are detected, the assay is reported as positive; if one target is detected, the assay is reported as inconclusive and is later confirmed reflexively by the real-time RT-PCR assay developed by the CDC at the Washington State Public Health Laboratory.

Descriptive statistics were used to summarize the data; results are reported as medians and interquartile ranges or means and standard deviations, as appropriate. Categorical variables were summarized as counts and percentages. No imputation was made for missing data. Analysis was performed with Stata 15.1 software (StataCorp).

During the period from February 24 through March 9, we identified 24 critically ill patients with confirmed Covid-19 infection at the nine hospitals surveyed. This number included all patients admitted to the ICU under the care of an intensivist at any time during the hospital stay. The demographic and clinical characteristics of the patients are shown in Table 1. The mean (±SD) age of the patients was 64±18 years (range, 23 to 97); 63% were men. The mean duration of symptoms before hospital admission was 7±4 days. None of the patients had recently traveled to a country with known transmission, such as China, South Korea, Iran, or Italy. A slight majority of patients (13 [54%]) had had recent contact with a person known to have been ill, but whether the sick contacts were infected with SARS-CoV-2 was not known because of the limited availability of testing at the time. Sixteen patients (67%) were admitted from home, and 6 patients (25%) were admitted from a skilled nursing facility. The most common symptoms on admission to the hospital were shortness of breath and cough, each of which occurred in 21 patients (88%). Documented fever was present in 12 patients (50%) on presentation at the hospital. Patient-level data are available in the Supplementary Appendix.

Chronic medical conditions were common in this critically ill population. Fourteen patients (58%) had diabetes mellitus and 5 (21%) had chronic kidney disease; 3 patients (14%) had asthma, and all 3 had recently received, as an outpatient, systemic glucocorticoids for a presumed asthma exacerbation before becoming critically ill. Five patients (22%) were current or former smokers and 1 patient (4%) had chronic obstructive pulmonary disease; 8 patients (33%) had more than one coexisting condition.

Table 2 shows the laboratory and radiologic findings in the patients on admission and during the ICU course. On admission, lymphocytopenia was common (in 75% of the patients), with a median lymphocyte count of 720 per cubic millimeter (interquartile range, 520 to 1375). Arterial lactate was 1.5 mg per deciliter or higher in 8 patients, and hepatic enzymes were 40 U per liter or higher in 9 patients. Troponin concentrations were elevated in 2 patients early in their ICU course (maximum value, 0.80 ng per deciliter).

A chest radiograph was obtained in 23 patients (96%) on ICU admission, and all the radiographs showed bilateral pulmonary opacities. No pleural effusions were seen. A computed tomographic (CT) scan of the chest was obtained in 5 patients (21%); four of the scans showed bilateral ground glass opacities, and one showed pulmonary nodules. Figure 1 provides representative images from a single patient, illustrating the rapid evolution of pulmonary opacities and the diffuse findings. A video showing the CT cross-sectional images of the chest is available at NEJM.org.

The performance of the local UW assay was similar to that of the CDC assay in comparison diagnostic testing. All patients had Covid-19 confirmed by an RT-PCR assay of a nasal swab. The UW assay returned one inconclusive result that was later confirmed as positive by the Washington State Public Health Laboratory.

Of the patients with laboratory-confirmed Covid-19, nearly all (23 patients [96%]) also had nasopharyngeal swabs sent to test for influenza and respiratory syncytial virus, and 21 patients (88%) had an extended-spectrum respiratory viral panel. None of the patients had a coinfection with another virus (see Table S1 in the Supplementary Appendix). Sputum samples from 15 patients were sent for bacterial culture, and all were negative for bacterial growth; blood samples from 20 patients were sent, and all remained negative. Bronchoscopy was performed in 4 patients. Two patients had bronchoscopy performed before diagnosis of Covid-19; bacterial and viral RT-PCR results were negative for other respiratory viruses. Two subjects had bronchoscopy performed late in the hospitalization for mucous plugging, without additional cultures.

Eighteen patients (75%) received invasive mechanical ventilation (Table 3). For patients who received mechanical ventilation, the Pao₂:Fio₂ ratios were consistent with moderate-to-severe ARDS. Pulmonary secretions were characterized as either moderate or thick and purulent in 14 patients (77%) during the first 7 days of mechanical ventilation. The median Fio₂ on day 1 of mechanical ventilation was 0.9 (interquartile range, 0.7 to 1.0), and the Fio₂ improved on day 3 to 0.6 (interquartile range, 0.5 to 0.7). The median driving pressure (the difference between plateau pressure and positive end expiratory pressure [PEEP]) on day 1 of mechanical ventilation was 13 cm of water (interquartile range, 11 to 17). During the first 3 days of mechanical ventilation, the median driving pressure was 12 to 13 cm of water. The median pulmonary compliance on day 1 was 29 ml per cm of water (interquartile range, 25 to 36). The pulmonary compliance improved during the first 3 days of mechanical ventilation, with median compliance on day 3 of 37 ml per cm of water (interquartile range, 25 to 42). Five patients (28%) were placed in a prone position, 7 (39%) received neuromuscular blockade, and 5 (28%) received inhaled pulmonary vasodilators to treat hypoxemic respiratory failure in ARDS. Tracheostomy was not completed in any of the patients.

Seventeen patients (71%) presented with concurrent hypotension requiring vasopressors, without clear evidence of secondary infection. Of these patients, 3 (18%) had transient hypotension after intubation; 14 (82%) had hypotension that was unrelated to intubation or that persisted for more than 12 hours after intubation. None of the echocardiograms completed in 9 patients (38%) showed new cardiac dysfunction. Seven patients received compassionate-use remdesivir as antiviral therapy, 1 patient received hydroxychloroquine, and 1 patient received lopinavir–ritonavir; no patient received systemic glucocorticoids or tocilizumab in the ICU.

All patients had at least 14 days of hospital follow-up. As of March 23, of the 24 patients, 12 (50%) had died, 4 (17%) had been discharged from the ICU but remained in the hospital, 3 (13%) were receiving mechanical ventilation and were still in the ICU, and 5 (21%) had been discharged from the hospital (Figure 2). A greater percentage of patients over 65 years of age had died than patients under 65 years of age (62% vs. 37%). The 12 deaths included 4 patients (17%) who had do-not-resuscitate orders in place before hospital admission for use in the event of cardiac arrest, and 6 additional patients (25%) had do-not-resuscitate orders that were instituted during their admission.

The median length of hospital stay among survivors was 17 days (interquartile range, 16 to 23), and the median length of ICU stay among survivors was 14 days (interquartile range, 4 to 17) (Table 3). The median duration of mechanical ventilation was 10 days (interquartile range, 7 to 12), and 6 patients (33%) had been extubated as of March 23, 2020. Three patients continued to receive ventilatory support, so the durations of mechanical ventilation and ICU stay are likely to be underestimates.