Abstract
Background
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States.
Methods
We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death.
Results
We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older.
Conclusions
Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.
Introduction
The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), has infected nearly 2 million patients worldwide, with over 100,000 deaths [1]. As of April 12, 2020, more than 550,000 patients have been diagnosed with COVID-19 in the United States (US) alone, with over 20,000 deaths. The US is already the leading country by number of people infected and is just behind – and soon to take over – Italy in the total number of deaths. Most of the research on COVID-19 has been published on patients in China, while a few describe populations in Europe [2]. Importantly, significant differences have been noted in the clinical and demographic features of COVID-19 patients in different regions of the world [3]. To date, there have been only three reports on COVID-19 patients in the US, two describing nursing home and senior facilities, and a third describing critically ill patients, all from Seattle, Washington [4], [5], [6]. Therefore, we aimed to study the clinical features and characteristics of all patients hospitalized with SARS-CoV2 infection, whether critically ill or stable, at our community hospital, in a mid-sized city in the Midwest region of the US.
Materials and methods
Study oversight
This retrospective study was designed by the principal investigator (S.A.). It was approved by the Institutional Review Board of UnityPoint Health and was done in compliance with the World Medical Association Declaration of Helsinki. Written informed consent was waived as this was a chart review study and the protocol was approved under an expedited review due to the urgent need to collect and report data. Data were collected and analyzed by two authors (S.A. and N.T.G.) who vouch for accuracy and completeness of data and for adherence of study to protocol. The other authors did not have access to raw data and provided essential support with interpretation of findings, drafting of manuscript, and revising the manuscript for critical intellectual content.
Data source
We queried our electronic medical record (EMR) database to search for all patients with a laboratory-confirmed diagnosis of COVID-19 seen at our health system until April 4, 2020. Nasal and pharyngeal swab specimens were collected either in the emergency room (ER) or during hospitalization, and a confirmed case of COVID-19 was defined as positive result on high-throughput sequencing or real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay, carried out according to a validated protocol. All patients who were hospitalized for COVID-19 were included. There were no exclusion criteria due to limited expected sample size.
We recorded data on symptoms at initial presentation from the ER or admitting history and physical notes. We then collected data on past medical history and comorbidities from the notes and chart review. Vital signs on admission were extracted from ER notes and EMR query. Fever was defined as forehead temperature >38°C (>100.4 F), and hypoxemia was defined as pulse oximetry reading from finger oximeter <90%. Hypotension was defined as mean arterial pressure (MAP) <65 mmHg and tachycardia was defined as heart rate (HR) >100 beats per minute (bpm). All laboratory values on the day of admission and during hospitalization were collected from the EMR. Laboratory values studied included complete blood counts, blood chemistry including renal and liver function, C-reactive protein (CRP), pro-brain natriuretic peptide (pro-BNP), creatinine kinase (CK), and cardiac troponin T (cTnT). Details of radiologic examinations – chest X-ray (CXR) and/or computed tomography (CT) scanning of the chest – were then extracted. The patients were deemed to have abnormal radiologic findings if mentioned in the report from the radiologist. Data were entered into a computer database and cross-checked twice.
Study outcomes
The primary composite endpoint was severe illness defined as the need for mechanical ventilation, use of inotrope support, intensive care unit (ICU) admission, or death. Secondary endpoints were development of acute respiratory distress syndrome (ARDS), acute renal failure, acute cardiac injury, and length of stay. Patients were deemed to have ARDS based on a clinical diagnosis by an attending pulmonologist. Acute renal injury was defined as an increase in serum creatinine >26.5 μmol/L (>0.3 mg/dL) or more than 30% increase in serum creatinine. Acute cardiac injury was defined as an increase in high-sensitivity cTnT above the 99th percentile value or suggestive changes in echocardiogram.
Statistical analysis
Continuous variables were expressed as median and range. Categorical variables were analyzed as counts and percentages. Fisher’s exact test was used to compare categorical variables, and the Mann-Whitney U test was used to compare continuous variables. A p-value <0.05 was considered statistically significant. No imputation was made for missing data. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) statistical software (IBM, Armonk, NY, USA).
Results
Demographic and clinical characteristics
Out of 42 patients who were diagnosed with COVID-19 at our hospital system in Des Moines area, 16 (38%) were hospitalized and included in our analysis, with eight (50%) meeting our primary endpoint. The baseline characteristics of these 16 inpatients are summarized in Table 1, which shows a comparison between patients requiring and not requiring ICU support. There were no differences between groups. Mean age was 65.5 years and 12 (75%) were male. A total of eight (50%) patients were obese [body mass index (BMI) ≥30 kg/m2]. All patients were of Caucasian origin.
Demographics and baseline characteristics of patients hospitalized with COVID-19.
| Variable | All Patients (n=16) | Primary endpoint met (n=8) | Primary endpoint unmet (n=8) | p-Value |
|---|---|---|---|---|
| Age, years, median (range) | 67 (38–95) | 67 (38–70) | 68.5 (41–95) | 0.43 |
| Sex | ||||
| Female | 4 (25%) | 3 (38%) | 1 (13%) | 0.56 |
| Male | 12 (75%) | 5 (63%) | 7 (88%) | |
| Social history | ||||
| Tobacco | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1.0 |
| Substance abuse | 3 (19%) | 2 (25%) | 1 (13%) | 1.0 |
| Comorbidities | ||||
| Obesity | 8 (50%) | 5 (63%) | 3 (38%) | 0.61 |
| Hypertension | 9 (57%) | 3 (38%) | 6 (75%) | 0.31 |
| Diabetes | 5 (31%) | 2 (25%) | 3 (38%) | 1.0 |
| Coronary artery disease | 3 (19%) | 2 (25%) | 1 (13%) | 1.0 |
| Congestive heart failure | 4 (25%) | 3 (38%) | 1 (13%) | 0.56 |
| Cerebrovascular disease | 2 (13%) | 1 (13%) | 1 (13%) | 1.0 |
| Chronic kidney disease | 6 (38%) | 3 (38%) | 3 (38%) | 1.0 |
| COPD | 2 (13%) | 1 (13%) | 1 (13%) | 1.0 |
| Malignancy | 3 (19%) | 2 (25%) | 1 (13%) | 1.0 |
| Autoimmune disease | 1 (6%) | 1 (13%) | 0 (0.0) | 1.0 |
| Symptoms/signs | ||||
| History of fever | 15 (94%) | 8 (100%) | 7 (88%) | 1.0 |
| Dry cough | 14 (88%) | 7 (88%) | 7 (88%) | 1.0 |
| Dyspnea | 13 (81%) | 7 (88%) | 6 (75%) | 1.0 |
| Chest pain | 1 (6%) | 1 (13%) | 0 (0.0%) | 1.0 |
| Nausea/vomiting | 2 (13%) | 0 (0.0%) | 2 (25%) | 0.46 |
| Diarrhea | 1 (6%) | 0 (0.0%) | 1 (13%) | 1.0 |
| Lightheadedness | 3 (19%) | 1 (13%) | 2 (25%) | 1.0 |
| Fatigue | 8 (50%) | 5 (63%) | 3 (38%) | 0.61 |
| Arthralgia | 4 (25%) | 2 (25%) | 2 (25%) | 1.0 |
| Headache | 4 (25%) | 2 (25%) | 2 (25%) | 1.0 |
| Sore throat | 2 (12.5%) | 1 (13%) | 1 (13%) | 1.0 |
| Anosmia | 3 (19%) | 1 (13%) | 2 (25%) | 1.0 |
| Dysgeusia | 3 (19%) | 1 (13%) | 2 (25%) | 1.0 |
| Heart rate, median (range), bpm | 94 (59–141) | 93 (71–141) | 94 (59–123) | 0.49 |
| Fever on presentation (n) | 6 | 4 (50%) | 2 (25%) | 0.60 |
| Mean arterial pressure, median (range), mmHg | 94 (73–134) | 94 (82–134) | 93 (73–132) | 0.71 |
| Pulse oximetry %, median (range) | 92 (63–100) | 87 (65–97) | 93 (63–100) | 0.17 |
| Sick contacts | 11 (69%) | 6 (75%) | 5 (63%) | 1.0 |
Unless otherwise stated, variables are given as n (%). COPD, chronic obstructive pulmonary disease.
A history of recent fever was reported by 15 (94%) patients, whilst six (38%) patients were febrile on presentation. Cough (88%) and dyspnea (81%) were the most common symptoms. Other symptoms such as chest pain (6.3%), headache (25%), and diarrhea (6.3%) were less common. A loss of smell and taste sensations were reported by three (19%) patients. A total of six (38%) patients had chronic kidney disease and one (6%) had end-stage renal disease. Only two (13%) patients had a history of chronic obstructive pulmonary disease (COPD). For cardiovascular comorbidities, nine (56.3%) had a history of hypertension, three (19%) had a history of coronary artery disease, three (19%) had a history of congestive heart failure, and two (13%) had a history of stroke. On presentation, five (31%) patients were tachycardic, six (38%) patients were hypoxemic, and none of the patients were hypotensive.
Laboratory and radiologic findings
Laboratory findings (Table 2) on admission showed leukocytosis in three (19%) patients with lymphopenia in 12 (75%) patients; three (19%) other patients were found to be thrombocytopenic. As much as eight patients (50%) were found to have hyponatremia on admission. A total of five (33%) patients (excluding the patient with end-stage renal disease) had elevated creatinine values on admission, while six (38%) had elevated aminotransferase values. Levels of CRP were increased in all 10 patients who were tested, while lactate dehydrogenase (LDH) activity was increased in four (80%) out of the five patients in whom it was measured. CXR revealed bilateral ground glass opacities in seven (44%) patients; five (31%) patients were reported to have interstitial edema vs. atypical infection, two (13%) were normal, and one (6%) patient did not have a CXR (Figure 1A). CT scan of the chest was performed in seven (44%) patients, with all of them showing multifocal ground glass opacities (Figure 1B).
Laboratory findings of patients hospitalized with COVID-19.
| Lab test | Normal range | Total (n=16) | Primary endpoint met (n=8) | Primary endpoint unmet (n=8) | p-Value |
|---|---|---|---|---|---|
| White blood cell count, 10×109/L | 4.00–11.0 | 7.38 (3.97–35.6) | 13.46 (5.19–35.6) | 6.4 (3.97–15.62) | 0.22 |
| Lymphocyte count, 10×109/L | 1.2–4.0 | 0.86 (0.75–1.59) | 0.84 (0.75–12.7) | 0.88 (0.75–1.59) | 0.62 |
| Neutrophil count, 10×109/L | 1.5–8.0 | 5 (2.4–17.2) | 6.7 (3.6–17.2) | 3.8 (2.4–13.8) | 0.15 |
| Hemoglobin, g/L | 110–170 | 145 (102–175) | 145 (116–175) | 151 (102–167) | 1.0 |
| Platelet count, 10×109/L | 150–450 | 211.5 (100–441) | 209.5 (118–441) | 211.5 (100–300) | 0.71 |
| Serum sodium, mmol/L | 136–145 | 135 (130–143) | 137.5 (130–143) | 133.5 (131–141) | 0.56 |
| Serum potassium, mmol/L | 3.5–5.0 | 4.25 (3.5–5.0) | 4.2 (3.5–4.7) | 4.35 (3.7–5.0) | 0.49 |
| Serum creatinine, mg/dL | 0.79–1.3 | 1.22 (0.79–7.68) | 1.14 (0.92–1.99) | 1.34 (0.79–7.68) | 0.79 |
| Lactate dehydrogenase, IU/L | 140–280 | 378 (209–867) n=5 | 622.5 (378–867) n=2 | 343 (209–537) n=3 | NA |
| C-reactive protein, mg/dL, median (range) | 0–0.5 | 16.75 (6.4–45.3) n=10 | 20.1 (11–45.3) n=6 | 8.1 (6.4–24) n=4 | NA |
| Alanine aminotransferase, IU/L | <41 | 24 (12–177) | 28.5 (12–177) | 20 (12–61) | 0.49 |
| Aspartate aminotransferase, IU/L | 8–48 | 32 (16–96) | 43.5 (35–96) | 25 (16–52) | 0.04a |
| Troponin T, ng/L | <11 | 10 (<6–282) n=10 | 14 (9–282) n=6 | 8 (<6–21) n=4 | NA |
| NT-pro BNP, pg/mL | <300 | 234 (38–459) n=3 | 234 (38–459) n=3 | n/a | NA |
Data presented as median (range). Labs presented are at admission or earliest time point in hospitalization. NT-pro BNP, N-terminal pro-brain natriuretic peptide. aDenotes statistical significance.
(A) CXR and (B) CT scan findings in one of the patients infected with COVID-19.
Clinical outcomes
None of the patients were lost to follow-up. Eleven patients were discharged in a stable condition from the hospital. The primary composite endpoint occurred in eight (50%) patients, with all needing ICU admission, five of whom necessitating intubation and mechanical ventilation. Three patients (19%) died from the illness (Table 3). Two patients were currently admitted while writing this report. Of the three patients who died, two refused further escalation of care and chose comfort care, and the third patient was given comfort care by his family. All three patients were more than 70 years old.
Complications and treatments of patients hospitalized with COVID-19.
| Total (n=16) | Primary endpoint met (n=8) | Primary endpoint unmet (n=8) | p-Value | |
|---|---|---|---|---|
| Complications | ||||
| Pneumonia | 12 (75%) | 8 (100%) | 4 (50%) | 0.45 |
| ARDS | 5 (31%) | 5 (63%) | 0 (0.0%) | 0.02a |
| Shock | 8 (50%) | 6 (75%) | 2 (25%) | 0.13 |
| Acute coronary syndrome | 4 (25%) | 4 (50%) | 0 (0.0%) | 0.07 |
| Arrhythmia | 1 (6%) | 1 (13%) | 0 (0.0%) | 1.0 |
| New-onset heart failure | 2 (13%) | 2 (25%) | 0 (0.0%) | 0.46 |
| AKI | 11 (69%) | 8 (100%) | 3 (38%) | 0.02a |
| Liver injury | 6 (38%) | 5 (63%) | 1 (13%) | 0.11 |
| Treatments | ||||
| Hydroxychloroquine | 11 (69%) | 8 (100%) | 3 (38%) | 0.02a |
| Azithromycin | 7 (44%) | 6 (75%) | 1 (13%) | 0.04a |
| Steroids | 3 (19%) | 3 (38%) | 0 (0.0%) | 0.2 |
| Invasive ventilation | 5 (31%) | 5 (63%) | 0 (0.0%) | 0.02a |
| Length of stay, days | 2 (1–12) | 6 (2–12)b | 2 (1–7) | 0.03a |
aDenotes a significant result. bn=6, two patients currently admitted. AKI, acute kidney injury; ARDS, acute respiratory distress syndrome.
ARDS was diagnosed in eight (50%) of the patients. Acute renal failure occurred in 11 (69%) patients, while six (38%) patients had elevation in aminotransferase values. A total of eight (50%) patients required vasopressor support due to shock. Acute cardiac injury occurred in three (19%) patients. Echocardiogram was performed in only three (19%) patients; one patient had a drop in left ventricular ejection fraction (LVEF) from 70% to 50%, the second patient had a drop in LVEF from 65% to 45%, and the third patient had normal LVEF 65%. None of the patients required coronary angiography.
Treatment and complications
Most patients received treatment with hydroxychloroquine (HCQ; 69%), and half of the patients received vitamin C. Azithromycin was given to 43% of the patients and few were treated with glucocorticoids (19%). Out of those who died, all three patients got HCQ and two received azithromycin. Infectious disease consultation was sought in seven patients, while cardiac consultation was sought in one patient who developed chest pain and ST-changes. This patient with chest pain was found to have atypical symptoms, had a borderline high-sensitivity cTnT value (21 ng/L), and was discharged in stable condition on day 4. This patient was on treatment with HCQ and azithromycin when chest pain occurred. Median length of stay was 2 (range 1–12) days for patients. Out of the two currently admitted, one patient is currently on mechanical ventilation, and has developed Clostridium difficile infection and ventilator-associated pneumonia.
Statistical analysis showed patients who had the primary endpoint met were more likely to have associated diagnosis of ARDS (p=0.02) and acute kidney injury (AKI) (p=0.02). They were also more likely to be treated with HCQ (p=0.02) and azithromycin (p=0.04). Median length of stay was significantly higher in patients who met the primary endpoint (6 vs. 2 days, p=0.03).
Discussion
To the best of our knowledge, this is the first study of clinical characteristics of hospitalized patients infected with SARS-CoV2 from a mid-sized city in the US, and from the Midwest where the disease has not reached its peak yet. Out of the 16 hospitalized patients, half of them required mechanical ventilation or admission to ICU. The mortality rate was 19% in the overall cohort; all the patients who died were above 70 years of age, with a mean age of 81 years. In patients above 70 years of age, the mortality rate was 60%.
Among the three patients who died, two had significant comorbidities. One patient had a history of hypertension, coronary artery disease, and congestive heart failure. The other patient had history of stroke, congestive heart failure, hypertension, diabetes, and cancer. The third patient had no comorbidities. As all three patients chose comfort measures and refused resuscitation, it may provide some insight into patient and provider attitude, especially among those who are older and infected with SARS-CoV2.
Our study has several implications. Most of the studies published in the literature have reported characteristics of patients infected with SARS-CoV2 living in China or Italy. There have been few reports from Washington State in the US, but mostly limited to seniors in assisted living centers and one on critically ill patients only. Our report sheds light on the characteristics of all patients hospitalized with SARS-CoV2 in a city which is not population dense, thus allowing for more easily implemented social distancing. Comparison of the characteristics of hospitalized patients with COVID-19 across the US is urgently needed. As differences in factors influencing outcomes have been observed between global populations [3], we hypothesize that factors such as pollution, social economic variables, genetics, ultraviolet (UV) exposure, population co-morbidities, and health status and infrastructure availability may all impact observed COVID-19 morbidity and mortality across different regions [3], [7]. To enable better clinical awareness and allocation of medical resources, understanding differences between patient characteristics across different regions is required. As there are no reports to date in the literature that describes the clinical features of hospitalized patients infected with COVID-19 in the US, especially outside of major metropolitan areas, our study will hopefully encourage other hospitals to publish their experiences, not only from major university hospitals but also from smaller and middle-sized community institutions. The findings of lymphocytopenia, thrombocytopenia, and abnormal renal function are similar to those reported recently in the literature in patients with SARS-CoV2 infection [8].
Our study has several important limitations. The biggest limitation of our study is the very small sample size. Hence, drawing meaningful inferences from our study is not advisable. However, as noted before, this is the first study of this nature to the best of our knowledge from the US and hence data can be important for policymakers. The situation is rapidly evolving in our city and state and we believe these results could change as more patients are hospitalized and more literature on treatments is reported. This was a retrospective study, and no exclusion criteria were applied. Hence, risk of selection bias cannot be excluded. The small number of patients inhibits detection of statistical differences between patients with and without severe disease, as such p-values should be interpreted cautiously. Lastly, all the patients in our cohort were Caucasian, which is in part reflective of the demographics of Iowa’s overall population which is 90% Caucasian; thus, our findings should not be extrapolated to other ethnicities. We also only studied patients who were hospitalized and cannot report if there are differences in characteristics and outcomes for patients who are being quarantined at home. Large prospective multi-ethnic studies are needed to further build on our data and provide insights into this ongoing pandemic in the US.
Conclusions
We present first reported data on all hospitalized patients in a community hospital in a mid-sized city in the Midwest region of the US infected with SARS-CoV2. Fever, cough, and dyspnea were the most common presenting symptoms. AKI occurred in a majority of patients and half of the hospitalized patients needed admission to ICU.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: Authors state no conflict of interest.
Informed consent: Written informed consent was waived as this was a chart review study and the protocol was approved under an expedited review due to the urgent need to collect and report data.
Ethical approval: It was approved by the Institutional Review Board of UnityPoint Health and was done in compliance with the World Medical Association Declaration of Helsinki.
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