Edited by: Ata Murat Kaynar, University of Pittsburgh, United States
Reviewed by: Mauricio Machado, Faculty of Medicine of São José Do Rio Preto, Brazil; Andre M. Japiassu, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Brazil
This article was submitted to Intensive Care Medicine and Anesthesiology, a section of the journal Frontiers in Medicine
†These authors have contributed equally to this work
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Information about severe cases of 2019 novel coronavirus disease (COVID-19) infection is scarce. The aim of this study was to report the clinical characteristics and outcomes of severe and critical patients with confirmed COVID-19 infection in Wenzhou city. In this single-centered, retrospective cohort study, we consecutively enrolled 37 RT-PCR confirmed positive severe or critical patients from January 28 to February 16, 2020 in a tertiary hospital. Outcomes were followed up until 28-day mortality. Fifteen severe and 22 critical adult patients with the COVID-19 infection were included. Twenty-six (68.4%) were men. Echocardiography data results suggest that normal or increased cardiac output and diastolic dysfunction are the most common manifestations. Compared with severe patients, critical patients were older, more likely to exhibit low platelet counts and high blood urea nitrogen, and were in hospital for longer. Most patients had organ dysfunction during hospitalization, including 11 (29.7%) with ARDS, 8 (21.6%) with acute kidney injury, 17 (45.9%) with acute cardiac injury, and 33 (89.2%) with acute liver dysfunction. Eighteen (48.6%) patients were treated with high-flow ventilation, 9 (13.8%) with non-invasive ventilation, 10 (15.4%) with invasive mechanical ventilation, 7 (18.9%) with prone position ventilation, 6 (16.2%) with extracorporeal membrane oxygenation (ECMO), and 3 (8.1%) with renal replacement therapy. Only 1 (2.7%) patient had died in the 28-day follow up in our study. All patients had bilateral infiltrates on their chest CT scan. Twenty-one (32.3%) patients presented ground glass opacity (GGO) with critical patients more localized in the periphery and the center. The mortality of critical patients with the COVID-19 infection is low in our study. Cardiac function was enhanced in the early stage and less likely to develop into acute cardiac injury, but most patients suffered with acute liver injury. The CT imaging presentations of COVID-19 in critical patients were more likely with consolidation and bilateral lung involvement.
Since December 2019, the outbreak of the novel coronavirus that originated in Wuhan has spread to more than 100 countries in Asia, Europe, North America, and the Middle East, and has become a global threat to human health. In February 2020, the World Health Organization designated the disease COVID-19 (
By February 17, 2020, there were 504 confirmed cases reported according to a government announcement in Wenzhou. Yang.et al presented the clinical characteristics and chest CT scan manifestations of most of the mild patients in Wenzhou, but did not report the severe COVID-19 characteristics (
For this single-centered, retrospective cohort study, we recruited adult inpatients (≥18 years old) admitted to The First Affiliated Hospital of Wenzhou Medical University, the only designated hospital in Wenzhou for patients with a severe or critical COVID-19 infection. The patients were consecutively enrolled from January 28 to February 16. Diagnosed with COVID-19 according to a laboratory reverse transcription polymerase chain reaction (RT-PCR) test, all these adult patients were confirmed as having the COVID-19 infection. The study was approved by The First Affiliated Hospital of Wenzhou Medical University Ethics Committee.
We retrospectively collected the medical records which included epidemiological, demographic, symptoms, laboratory results, complications, outcome, and treatment data. We collected the admission data of these patients. Laboratory confirmation of COVID-19 was done by real-time RT-PCR methods.
The data on age, sex, exposure history, comorbidity (hypertension, diabetes cardiovascular disease, chronic kidney disease, chronic liver disease, cerebrovascular disease, hematological diseases), symptoms from onset to hospital admission (fever, cough, expectoration, dyspnea, muscle pain, headache, sore throat, chill, diarrhea, fatigue), laboratory results on admission (hemoglobin, white blood cell count, neutrophil count, lymphocyte count, monocyte count, platelet, d-dimer, creatine kinase, creatine kinase–mb, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, hypersensitive troponin I, procalcitonin, brain natriuretic peptide, lactate, albumin, total cholesterol, cytokine levels, T lymphocyte cell subsets), treatment [Glucocorticoid therapy, Immunoglobulin therapy, Thymosin, Thaliduan, Antibiotic treatment, Antiviral treatment, Oxygen Treatment, Prone Position Ventilation, Continuous renal replacement therapy (CRRT)], clinical outcome [Sepsis, Septic Shock, Acute respiratory distress syndrome (ARDS), Acute cardiac injury, Acute kidney injury, Acute liver injury, Secondary infection, Acidosis, Prognosis], and radiological and echocardiography data and as well as living status were collected. The Acute Physiology and Chronic Health Evaluation II (APACHEII) and SOFA score system were used to assess pneumonia severity.
Sepsis and septic shock were diagnosed according to sepsis-3.0 definition (
Continuous variables were presented as medians (IQR) or mean (SD) and compared with the Mann–Whitney
By February 16, 2020, 37 severe or critical patients had been admitted to The First Affiliated Hospital of Wenzhou Medical University with confirmed COVID-19 pneumonia, of whom, 15 (40.5%) severe and 22 (59.5%) critical. The mean age was 57 years (21–93), 14 (21.5%) patients were older than 60 years old. Twenty-six (68.4%) patients were men. Ten (26.3%) patients recently visited Wuhan or Hubei, and 13 (34.2%) had contact with Wuhan residents, 4 (10.5%) had been exposed to a confirmed case, 11 (28.9%) patients had no definite causes. The most common chronic diseases were hypertension [14(36.8%)] and diabetes [8(21.1%)]. Twenty-two patients had increased serum levels of aspartate aminotransferase. All of the 37 patients had bilateral infiltrates on their chest CT scan. The most common symptoms were fever (100%), cough (78.4%), and expectoration (43.2%). The median APACHE II score and SOFA score of all patients were 8.0 (4.5–10.5) and 1 (0–3) (detail in
Baseline characteristics of patients infected with COVID-19.
Age, median (IQR), year | 55 (48–68) | 54 (48–60) | 56 (47–73) | 0.132 |
>60 year | 14 (21.5%) | 3 (20.0%) | 10 (45.5%) | 0.111 |
Male gender, |
26 (68.4%) | 11 (73.3%) | 15 (76.2%) | 0.736 |
hospital-stay, mean (SD), d | 30.4 (14.7) | 25.1 (15.8) | 31.9 (11.1) | 0.134 |
Recently visited Wuhan or hubei | 10 (26.3%) | 4 (26.7%) | 6 (27.3%) | 0.967 |
Contact with Wuhan residents | 13 (34.2%) | 7 (46.7%) | 6 (27.3%) | 0.225 |
Exposure to patients |
4 (10.5%) | 1 (6.7%) | 3 (13.6%) | 0.503 |
No definite causes | 11 (28.9%) | 4 (26.7%) | 7 (31.9%) | 0.875 |
Hypertension | 14 (36.8%) | 6 (40.0%) | 8 (36.4%) | 0.823 |
Diabetes | 8 (21.1%) | 3 (20%) | 5 (36.4%) | 0.843 |
Cardiovascular disease | 1 (2.6%) | 0 | 1 (2.6%) | – |
Chronic kidney disease | 1 (2.6%) | 0 | 1 (2.6%) | – |
Chronic liver disease | 1 (2.6%) | 0 | 1 (4.5%) | – |
Cerebrovascular disease | 1 (2.6%) | 0 | 1 (2.6%) | – |
Hematological diseases | 1 (2.6%) | 0 | 1 (2.6%) | – |
Fever | 37 (100%) | 15 (100%) | 22 (100%) | – |
Cough | 29 (78.4%) | 11 (73.3%) | 18 (81.8%) | 0.835 |
Expectoration | 16 (43.2%) | 6 (40%) | 10 (45.5%) | 0.742 |
Dyspnea | 8 (21.6%) | 2 (13.3%) | 6 (27.3%) | 0.545 |
Muscle pain | 4 (10.8%) | 2 (13.3%) | 2 (9.1%) | 1.000 |
Headache | 2 (5.4%) | 2 (13.3%) | 0 (0%) | 0.158 |
Sore throat | 4 (10.8%) | 3 (20%) | 1 (4.5%) | 0.344 |
Chill | 8 (21.6%) | 5 (33.3%) | 3 (13.6%) | 0.307 |
Diarrhea | 2 (5.4%) | 1 (6.7%) | 1 (4.5%) | 1.000 |
Fatigue | 7 (18.9%) | 2 (13.3%) | 5 (22.7%) | 0.773 |
APACHEII, median (IQR) | 8 (4.5–10.5) | 7 (4–9) | 10 (6–13) | 0.042 |
SOFA, median (IQR) | 1 (0–3) | 0 (0–2) | 2 (1–3) | 0.012 |
Most patients had organ dysfunction during hospitalization, including 11 (29.7%) with ARDS, 8 (21.6%) with acute kidney injury, 17 (45.9%) with acute cardiac injury, and 33 (89.2%) with acute liver dysfunction. Only 3 patients (8.1%) had hypersensitive troponin I increased on admission. Eighteen (48.6%) patients were treated with high-flow ventilation, 9 (13.8%) with non-invasive ventilation, 10 (15.4%) with invasive mechanical ventilation, 7 (18.9%) with prone position ventilation, 6 (16.2%) with extracorporeal membrane oxygenation (ECMO), 3 (8.1%) with renal replacement therapy. 37 (100%) received antibacterial agents and antiviral treatment, 21 (56.8%) patients received glucocorticoids. Thymosin was treated in 21 (56.8%) of the patients. Thaliana was treated in 15 (40.5%) of the patients (Details in
Laboratory findings of patients infected with COVID-19 on admission to ICU.
Hemoglobin, g/L | 115–150 | 127.0 (112–142) | 128.0 (119–150) | 126.0 (109–139) | 0.202 |
White blood cell count, × 109/L | 3.5–9.5 | 7.8 (5.3–11.4) | 5.6 (4.8–8.0) | 9.3 (6.9–11.8) | 0.135 |
Neutrophil count, × 109/L | 1.8–6.3 | 6.1 (3.3–9.4) | 4.8 (2.4–7.1) | 7.0 (4.6–9.6) | 0.197 |
Lymphocyte count, × 109/L | 1.1–3.2 | 0.7 (0.5–1.0) | 0.8 (0.6–1.3) | 0.7 (0.5–1.0) | 0.449 |
Monocyte count, × 109/L | 0.1–0.6 | 0.5 (0.3–0.7) | 0.4 (0.3–0.7) | 0.5 (0.3–0.9) | 0.266 |
Platelet count, × 109/L | 125–350 | 207.0 (114–259) | 253.0 (191–289) | 179.0 (106–252) | 0.005 |
D-dimer, mg/L | 0–0.5 | 1.1 (0.7–1.7) | 1.0 (0.7–1.2) | 1.2 (0.8–1.8) | 0.329 |
Creatine kinase, U/L | 20–140 | 129.0 (63–258) | 90.0 (52–244) | 152.5 (69–355) | 0.111 |
Creatine kinase–MB, U/L | 0–16 | 9.0 (7–13.5) | 8.0 (6–10) | 11.0 (7.8–12.3) | 0.062 |
Alanine aminotransferase, U/L | 7–40 | 31.0 (21.5–61.5) | 29.0 (24–42) | 38.5 (20.8–69.5) | 0.596 |
>40, |
16 (43.2%) | 5 (33.3%) | 11 (50.0%) | 0.315 | |
Aspartate aminotransferase, U/L | 13–35 | 41.0 (30.5–59.0) | 35.0 (30–44) | 50.0 (34.2–69.0) | 0.060 |
>35, |
22 (57.9%) | 6 (40%) | 16 (72.7%) | 0.047 | |
Gamma-glutamyl transferase, U/L | 10–60 | 43.0 (26.0–96.5) | 33 (24–95) | 49.5 (26.8–101.0) | 0.284 |
>60, |
16 (43.2%) | 5 (33.3%) | 10 (45.5%) | 0.460 | |
Total bilirubin, mmol/L | 0–20 | 13.0 (9–16) | 14.0 (9–15) | 11.5 (8.0–16.3) | 0.655 |
Blood urea nitrogen, mmol/L | 2.5–6.1 | 5.0 (3.9–6.0) | 4.0 (3–5.1) | 5.24 (4.4–6.9) | 0.018 |
Creatinine, μmol/L | 46–92 | 60.0 (55–76) | 57.0 (52–63) | 64.5 (57.5–80.8) | 0.044 |
Hypersensitive | |||||
troponin I, ug/L ≥0.015, No. (%) | 0–0.015 | 3 (8.1%) | 0 | 3 (13.6%) | 0.202 |
Procalcitonin, ng/mL ≥0.05, No. (%) | <0.05 | 2 (5.4) | 1 (6.7%) | 1 (4.5%) | 0.951 |
Brain natriuretic peptide, pg/ml | 0–100 | 39.0 | 31.0 (14–58) | 64.5 (15.0–156.0) | 0.056 |
Lactate, mmol/L | 0.7–2.1 | 2.4 (1.9–3.1) | 2.8 (2.4–3.1) | 2.2 (1.7–3.0) | 0.143 |
Albumin, g/l | 31.9 (29.1–34.6) | 32.8 (30.5–34.9) | 30.5 (28.5–33.9) | 0.279 | |
Total cholesterol, mmol/l | 3.9 (3.5–4.6) | 4.4 (3.7–5.2) | 3.8 (3.4–4.4) | 0.075 | |
IL-2, pg/ml | <3.1 | 0.9 (0.6–1.1) | 0.9 (0.6–1.1) | 0.9 (0.7–1.1) | 0.357 |
IL-4, pg/ml | <3.0 | 0.8 (0.6–1.4) | 1.0 (0.5–1.4) | 0.7 (0.6–1.4) | 0.843 |
IL-6, pg/ml | <3.0 | 12.7 (3.49–80.2) | 4.9 (2.5–52.4) | 38.6 (4.6–103.1) | 0.115 |
IL-10, pg/ml | <4.1 | 5.9 (3.6–14.6) | 4.3 (3.1–7.1) | 11.4 (3.7–18.5) | 0.367 |
TNF-a, pg/ml | <3.1 | 0.2 (0.1–0.5) | 0.2 (0.1–0.5) | 0.2 (0.1–0.5) | 0.716 |
T cell(CD3+), % | 53.7–80.9 | 53.6 (42.5–66.3) | 53.6 (41.3–64.1) | 54.3 (42.5–67.9) | 0.952 |
CD4+T cell, % | 27.4–49.2 | 32.3 (27.8–40.1) | 32.2 (28–40.2) | 33.3 (27.4–40.3) | 0.962 |
CD8+T cell, % | 15.8–37.5 | 18.3 (12.5–27.1) | 18.3 (10.9–28.0) | 18.3 (13.4–24.5) | 0.910 |
B cell, % | 5.1–20.3 | 22.2 (14.2–29.4) | 20.7 (12.8–24.9) | 23.9 (14.8–40.8) | 0.167 |
NK cell, % | 6.7–30.9 | 13.9 (10.8–27.8) | 18.7 (13.8–28.5) | 12.9 (7.7–19.1) | 0.069 |
Treatments and outcomes of patients infected with COVID-19.
Glucocorticoid therapy | 21 (56.8%) | 3 (20%) | 18 (81.8%) | <0.001 |
Immunoglobulin therapy | 19 (51.4%) | 7 (46.7%) | 12 (54.5%) | 0.638 |
Thymosin | 21 (56.8%) | 4 (26.7%) | 17 (77.3%) | 0.002 |
Thaliduan | 15 (40.5%) | 4 (26.7%) | 11 (50%) | 0.156 |
Antiviral treatment | 37 | 15 | 22 | – |
Antibiotic treatment | 37 | 15 | 22 | – |
High flow | 18 (48.6%) | 0 | 18 (81.8%) | <0.001 |
NIV | 9 (13.8) | 0 | 9 (40.9%) | 0.005 |
IMV | 10 (15.4%) | 0 | 10 (45.5%) | 0.002 |
ECMO | 6 (16.2%) | 0 | 6 (27.3%) | 0.063 |
Prone Position Ventilation | 7 (18.9%) | 0 | 7 (31.8%) | 0.028 |
CRRT | 3 (8.1%) | 0 | 3 (13.0%) | – |
Sepsis | 34 (91.9%) | 12 (80%) | 22 (100%) | 0.059 |
Septic Shock | 6 (16.2%) | 0 | 6 | 0.063 |
ARDS | 11 (29.7%) | 0 | 11 (50%) | <0.001 |
Acute cardiac injury | 17 (45.9%) | 1 (6.7%) | 16 (72.7%) | <0.001 |
Acute kidney injury | 8 (21.6%) | 1 (6.7%) | 7 (31.8%) | 0.156 |
Acute liver injury | 33 (89.2%) | 12 (80.0%) | 21 (95.5%) | 0.344 |
Secondary infection | 13 (35.1%) | 1 (6.7%) | 12 (54.5%) | 0.003 |
Acidosis | 10 (27.0%) | 0 | 10 (45.5%) | 0.002 |
28-day mortality | 1 (2.7%) | 0 | 1 (4.5%) |
Among the 37 severe or critical patients with the COVID-19 infection, only 1 (2.7%) patient died, after 14 days. Compared with severe patients, critical patients were older [52.4 (21–81) vs. 60.1 (39–93)], and had high APACHE II [7 (4–9) vs. 10 (6–13)], and SOFA scores [0 (0–2) vs. 2 (1–3)]. Of the 22 critical patients, 13 (59.1%) patients were discharged, 8 (36.4%) patients remained in hospital (Details in
The radiological and echocardiography data on admission are summarized in
Radiological and echocardiography data of patients infected with COVID-19.
GGO | 21 (32.3%) | 11 (66.7%) | 10 (45.5%) |
consolidation | 1 (1.5%) | 0 | 1 (4.5%) |
mixed | 15 (23.1%) | 4 (27.6%) | 11 (50.0%) |
Peripheral | 15 (40.5%) | 9 (60.0%) | 6 (27.3%) |
Central and peripheral | 22 (59.5%) | 6 (40.0%) | 16 (72.7%) |
Pleural effusion | 3 (4.6%) | 2 (13.3%) | 1 (4.5%) |
Echocardiography, |
30 | 10 | 20 |
cardiac output, CO L/min | 6.0 (1.6) | 6.6 (1.6) | 5.7 (1.5) |
stroke volume, SV ml | 75.4 (16.7) | 79.6 (18.7) | 73.4 (15.6) |
Ejection fraction, EF % | 63.5 (4.8) | 66.0 (3.5) | 62.3 (5.0) |
Diastolic dysfunction | 17 (56.7%) | 7 (70%) | 10 (50%) |
pulmonary hypertension | 2 (6.7%) | 0 | 2 (10%) |
Left atrial enlargement | 17 (56.7%) | 5 (50%) | 12 (60%) |
Mitral regurgitation | 7 (23.3%) | 0 | 7 (35%) |
Tricuspid regurgitation | 4 (13.3%) | 0 | 4 (20%) |
This retrospective cohort study presented severe and critical patients' clinical characteristics and outcomes in Wenzhou city who were hospitalized with the COVID-19 infection. In this study, we found higher age, and higher SOFA and APACHE II scores on admission were associated with disease severity. Additionally, elevated levels of Blood urea nitrogen, decreased levels of platelet were more common in critical COVID-19 patients. To our best knowledge, this retrospective cohort study is the first report to compare severe and critical patients from one city with COVID-19 outside Wuhan.
Comparing our data with those published from Wuhan, we found that patients in Wenzhou city had a milder infection (
Liver complications, including elevated levels of ALT, AST, or bilirubin are common in patients with sepsis. Several large-scale case studies have reported the clinical features of patients with COVID-19 (
Based on previous studies, nearly 17% of patients had acute cardiac injury, with a high sensitive cardiac troponin I increase or abnormalities seen in electrocardiography and echocardiography (
The APACHEII and SOFA scores reflect the state and degree of illness severity and multi-organ dysfunction, respectively, the SOFA score is also a good diagnostic marker for sepsis (
Our study has some limitations. Firstly, several patients in our study still remain in the hospital, the final outcome is not complete, but those patients have survived longer than 28 days. Secondly, several patients were transferred from other medical institutions and may have received effective intervention before being transferred, this hospital admission may not be their first admission. Thirdly, only 37 patients were included, our conclusion might be limited by the sample size.
The mortality of critically ill patients with COVID-19 is low in our study. Cardiac function was enhanced in the early stage and therefore less likely to develop into acute cardiac injury, but most patients suffered with acute liver injury. The CT imaging presentations of COVID-19 in critical patients were mostly patchy ground glass opacities in the peripheral areas under the pleura, and more likely with consolidation, and bilateral lung involvement.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The study was approved by the First Affiliated Hospital of Wenzhou Medical University Ethics Committee.
J-YP: design of the study. S-ZQ and WH: collection of data. L-m: data management. C-l and Z-f: analysis. S-ZQ: wrote the paper. J-YP: critical revision of the article. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.