The US Centers for Disease Control and Prevention (CDC), the Georgia Department of Public Health (DPH), and 3 hospital networks within Georgia partnered to review patient medical records at 8 Georgia hospitals. Seven hospitals were in metropolitan Atlanta, and 1 was in southern Georgia; they comprised academic medical centers, a public teaching hospital, and community hospitals; all provided tertiary care.

Hospitals provided lists of patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test who were admitted during March 1–March 30, 2020 (n = 698). Clinicians reviewed electronic medical records on a convenience sample of sequentially identified adults aged ≥18 years from each hospital’s patient list [19]. We conducted as many initial chart abstractions as possible through April 20 (n = 305). Transfers between participating hospitals and multiple admissions of the same patient (10 patients had a single readmission, and 1 had 2 readmissions) were analyzed as a single hospitalization.

Because some patients were still hospitalized at the time of initial data abstraction, all patient records were re-examined on May 8 to assess outcomes. Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the CDC [20, 21]. Medical records were examined for clinical, laboratory, and radiologic data, and audits were performed on all chart abstractions to correct data missingness and identify implausible values. This investigation was determined by the CDC and DPH to be public health surveillance [22].

Admission vital signs and laboratory values were abstracted for all patients. For serial vital signs and laboratory data, patients were stratified by phenotype, and we plotted the daily average among patients by stratum, inversely weighting observations by the number of observations per patient per day. Wilcoxon rank-sum tests were used to evaluate differences in distributions.

Analyses and visualizations were conducted using R software, version 3.6.2 (Vienna, Austria).

Baseline characteristics of patients have been previously described. Among 305 patients, the median age (interquartile range [IQR]) was 60 (46–69) years, 51% were female, and 83% were non-Hispanic Black. One hundred nineteen patients (39%) were admitted to the intensive care unit (ICU), 92 (30%) received invasive mechanical ventilation (IMV), and 51 (17%) died. Two hundred eighty-seven (94%) were initially admitted for confirmed or suspected COVID-19. Among 18 patients not originally admitted with suspected COVID-19, SARS-CoV-2 was detected by RT-PCR at median hospital day 2; 7 were diagnosed ≥5 days after admission (range, 5–38 days).

Among the subset of 287 patients whose initial reason for admission was COVID-19, the median time from symptom onset to admission (IQR) was 7 (4.0–9.0) days. While most presented with fever or respiratory symptoms (Figure 1), there were 10 (3%) patients who did not present with fever, cough, or shortness of breath. Of these 10, 7 developed a fever within 2 days of admission, and 5, all of whom were >70 years old, presented with new or worsened altered mental status. After febrile respiratory syndromes, syndromes involving myalgia, fatigue, or gastrointestinal symptoms were the most common. Diarrhea occurred in 75 (26%) patients, usually in combination with fever or respiratory symptoms. Nineteen (7%) patients presented with altered mental status (median age [range], 79 [62–95] years).

Median length of stay (LOS) (IQR) was 7.5 (4.0–14.0) days for patients discharged alive and 11.0 (7.5–18.0) days for patients who died. Among ICU patients (n = 119), the median duration of ICU stay (IQR) was 8.0 (5.0–12.50) days (Figure 2). ICU admission occurred at a median (IQR) of hospital day 3.0 (2.0–4.0), with IMV initiation at a median (IQR) of hospital day 3.5 (2.0–5.0) and vasopressor initiation at median (IQR) hospital day 5.0 (3.0–8.0). The median duration of IMV (IQR) was 9.0 (5.0–12.0) days. Among 119 ICU patients, 13 (11%) underwent prone positioning while ventilated, 6 (5%) received a tracheostomy, and 2 (2%) received extracorporeal membrane oxygenation.

In addition to supportive therapy, hydroxychloroquine was administered to 117 (38%) patients, of whom 37 did not require intensive care. Corticosteroids were initiated in 17% of patients. Eight patients received lopinavir/ritonavir, and none received tocilizumab. No patients received immunomodulatory therapies (eg, interleukin [IL]-1 inhibitors and IL-6 blockers). Antibiotics covering common community-acquired pathogens were administered to 95% within 48 hours after admission (99% of ICU patients); 51% received antibiotics after 48 hours, mostly as an escalation of empiric antibiotics. Data on anticoagulation use were not available for analysis.

AKI was diagnosed by the treating clinician in 124 (41%) patients; 22 (7%) required renal replacement therapy (RRT) during hospitalization (Table 1). VTEs were documented in 17 (6%) patients, including 11% of ICU patients; arterial thrombotic events (stroke, peripheral artery thrombosis, or acute coronary syndrome) were seen in 7 (2%) patients. Among patients admitted to the ICU, 69 (58%) had a diagnosis of shock; of these, 58 (84%) died.

Viral coinfections were uncommon (n = 10); the most common viral coinfection was with influenza (n = 8 [3%], 275/305 were tested). Bacterial coinfections, defined as positive culture with corresponding antibacterial treatment, were identified in 32 (11%) patients. Among 74 patients tested for either pathogen, no urine Legionella or Streptococcus pneumoniae antigen tests were positive. Seven patients had documented hospital-acquired or ventilator-associated pneumonia. Eight (3%) patients had bacteremia; the most common pathogens were coagulase-negative Staphylococcus species (Supplementary Table 1).

The partitioning around medoids analysis grouped patients into 6 patterns (clusters A–F, Figure 3). Mortality was highest in cluster A (49%, n = 53) compared with other clusters (<20%). Proportions of IMV (89%), shock (81%), and AKI (87%) were also highest in cluster A. This cluster had the highest median age (67 years), the highest prevalence of cardiovascular disease (64%), and was predominantly male (60%). Cluster A patients had elevated median peak CRP, LDH, CPK, D-dimer, PTT, AST, ALT, and creatinine compared with the cohort (Supplementary Figure 1). The median nadir absolute lymphocyte count for this cluster was relatively low (0.72 cells/mm³).

Clusters B (n = 34) and C (n = 39) had a high prevalence of AKI (>70%) and similar mortality rates (19% and 18%, respectively). Cluster B was distinguished by high prevalence of diabetes (79%) and diarrhea as a presenting symptom (79%), and cluster C patients had a high prevalence of chills (69%). There were 2 clusters (D, n = 29, and E, n = 61) that were predominantly female. These clusters differed by comorbidities: Cluster D had higher prevalence of diabetes, chronic lung disease, and severe obesity (BMI ≥40). Cluster E had the lowest prevalence of mechanical ventilation (5%).

Cluster F (n = 71) patients were the youngest (median age, 43 years) and had few comorbidities. There were few complications reported in these patients relative to the cohort. While 15% of these patients required mechanical ventilation, this cluster had the lowest mortality rate (1%).

Treatment and co-infections by cluster are shown in Supplementary Table 2. Antibiotic use overall was >90% among all clusters, although continued antibiotic use >48 hours after admission was higher among cluster A patients (87%) than others (range, 33%–41%). Cluster A had the highest proportions of hydroxycloroquine (69.8%) and azithromycin (83.0%) use. The proportions of patients receiving corticosteroids and remdesivir were not distinctively different in cluster A. The highest proportions of bacterial co-infections were seen in clusters A (26.4%) and D (17.2%); all patients with ventilator-associated pneumonia were in cluster A, accounting for 5.7% of this group.

Serial vital signs and laboratory data were available for 240 (81%) patients admitted to 5 of the hospitals. The value distribution and number of observations per patient stratified by LOS are shown in Supplementary Table 3. Differences in laboratory values and vital signs were observed in patients with the severe cluster A phenotype compared with the rest of the cohort (Figure 4). Patients in cluster A had a higher heart rate, respiratory rate, and temperature and lower mean arterial pressure (MAP) compared with patients in other clusters. While CRP was most elevated at approximately hospital day 7 in all patients, those in cluster A had higher mean CRP values throughout the hospital course compared with those in other clusters (207 vs 116 mg/L; P < .001). Mean creatinine and BUN were also more elevated in cluster A throughout the hospital course (creatinine 2.3 vs 1.5 mg/dL; P < .001). D-dimer was higher among cluster A patients in the first days of hospitalization. While mean WBC count was higher in cluster A patients (10.8 vs 6.9 × 10⁹/L; P < .001), median nadir absolute lymphocyte count was lower compared with patients in other phenotype clusters (0.71 vs .95 × 10⁹/L; P = .009). AST and ALT were elevated in cluster A patients, particularly at the beginning of the hospital course and during the second week of hospitalization, and there was a 2:1 ratio in average values of AST to ALT. Alkaline phosphatase was similar between cluster A and other clusters until the second week of hospitalization, when cluster A patients had more elevated values compared with the rest of the cohort.

Final outcomes were known for 297 (97%) patients. Eleven patients were readmitted to the same hospital system during the data collection period; 6 were readmitted with worsening COVID-19 symptoms, 3 with complaints likely unrelated to COVID-19, and in 2 patients cause of readmission was not available. Among 51 patients (17%) with a recorded cause of death, the primary event leading to death was respiratory failure in 26 (51%) and multiorgan system failure or shock in 13 (26%). Among patients who received IMV, mortality was 44%.

Among 246 patients discharged alive, 205 (83%) were discharged to their prehospital level of care, and 38 (15%) were discharged to a higher level of care than their prehospital baseline (eg, someone who was previously independent at home being discharged home with new services or to a rehabilitation facility) (Supplementary Table 4). There were 37 (12%) patients with new oxygen requirements upon discharge. Three patients were discharged for prolonged mechanical ventilation weaning to long-term acute care facilities, 4 were discharged with a tracheostomy, and 6 were discharged with new RRT needs.