key: cord-1036308-imidgnng authors: Hu, Rui; Han, Chaofei; Pei, Shiyao; Yin, Mingzhu; Chen, Xiang title: Procalcitonin levels in COVID-19 patients date: 2020-06-10 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.106051 sha: 9e1ed69fa47c120076129f08d1d8af947cdd4506 doc_id: 1036308 cord_uid: imidgnng Coronavirus disease 2019 (COVID-19) is turning into a pandemic. Here, we analyzed 95 patients infected with SARS-CoV-2. Sixty-two moderate patients, 21 severe patients and 12 critical patients (6 patients died) were included in our study. Our results showed that the mean serum levels of procalcitonin in severe patients were over 4 times higher than those in moderate patients, and they were over 8 times higher in critical patients than in moderate patients. For the discharged patients, both high-normal procalcitonin levels and abnormal procalcitonin levels decreased during recovery. However, in the death cases, the serum levels of procalcitonin increased as the disease worsened. We demonstrate that procalcitonin may be an indicator of severity and may contribute to determining the severity of patients infected with COVID-19; moreover, serial procalcitonin measurements may be useful in predicting prognosis. Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout more than 200 countries, areas or territories [1] . SARS-CoV-2, as a novel positive-sense RNA virus, has 79% homology with severe acute respiratory syndrome (SARS-CoV) and 50% homology with Middle East respiratory syndrome (MERS-CoV) [2] , but it is far more infectious than both. As of May 24, 2020, a total of 5 103 006 people were confirmed to have the disease, and approximately 333 401 deaths occurred [1] . COVID-19 has become a pandemic. Procalcitonin (PCT) is the 116-amino acid precursor of the hormone calcitonin. Recently, several studies reported that evaluated PCT is positively associated with the severity of COVID-19 [3] [4] [5] [6] . A Page 3 meta-analysis also demonstrated that procalcitonin values are related to an approximately 5-fold higher risk of severe SARS-CoV-2 infection [7] . To improve the diagnosis in order to distinguish between severe/critical patients and moderate patients with COVID-19 and to better predict prognosis, we aimed to investigate the role of the changes in procalcitonin (PCT) values here. This retrospective cohort study initially enrolled a total of 95 patients who met the inclusion criteria from January 30 to March 17, 2020, from the Wuhan Union and Tongji hospitals of Huazhong University of Science and Technology. The inclusion criteria were as follows. All patients were adults (men and non-pregnant women). All the patients were laboratory confirmed cases in our study. The diagnostic criteria of COVID-19 were based on the New Coronavirus Pneumonia Prevention and Control Program (6th edition) published by the National Health Commission of China [8] . Written informed consent was waived by the Ethics Commission of the designated hospital due to the emergency of COVID-19. According to the New Coronavirus Pneumonia Prevention and Control program (6th edition) [8] , COVID-19 is classified into four types: mild, moderate, severe, and critical pneumonia. Mild pneumonia means asymptomatic infection or mild clinical symptoms without abnormal chest imaging findings. Moderate pneumonia is defined as having both clinical symptoms and abnormal chest imaging findings. Patients are diagnosed as having severe pneumonia when the disease progresses to meet any of the following conditions: (1) significantly increased respiration rate (RR) of ≥ 30/min; (2) oxygen Page 4 saturation ≤ 93% in the resting state; or (3) PaO2/FiO2 ≤ 300 mmHg (1 mmHg = 0.133 kPa). Critical pneumonia occurs when the disease progresses rapidly with any of the following conditions: (1) respiratory failure, which requires mechanical ventilation; (2) shock; or (3) other organ failures in need of intensive care unit (ICU) monitoring and treatment. Fever was defined when the axillary temperature was equal to or above 37.5°C. Hospital stay was described as the length. Bacterial infection was defined according to the clinical symptoms, increased white blood counts, PCT levels, and CRP levels or positive results of bacterial culture. We obtained demographic, clinical and laboratory data from electronic medical records with a data collection form. Chemiluminescence was used to measure PCT. Continuous variables with a normal distribution are expressed as the mean ± standard deviation (SD) and were compared with analysis of variance (ANOVA). Continuous data with skewed distributions were compared with the Wilcoxon rank sum test. Categorical variables are summarized as counts (percentages). All analyses were performed with SPSS software, version 23. A P value less than 0.05 was considered statistically significant. A total of 95 patients (39 males and 56 females) infected with COVID-19 were included in our study. According to their severity of pneumonia when they were admitted to the hospital, they were classified into 3 groups including the moderate (n=62), severe (n=21) and critical (n=12) groups. The total mean age was 57.6±14.6 years. The mean age was 54.0±14.9 years in the moderate group, 65.0±9.8 years in the severe group and 62.3±13.8 years in the critical group. 1.1%] ). There was no history of other diseases in these patients. The clinical symptoms on admission of the patients in the three groups were compared in Table S1 . The most common symptoms at onset of illness were fever (68/95, 71.6%), cough (54/95, 56.8%), and dyspnea (48/95, 50.5%); less common symptoms were fatigue (32/95, 33.7%), expectoration (26/95, 27.4%), nausea (14/95, 14.7%), myalgia (14/95,14.7%), vomiting (11/95, 11.6%), diarrhea (9/95, 9.5%) , dizziness (7/95, 7.4%), sore throat (5/95, 5.3%), headache (3/95, 3.2%), and abdominal pain (2/95, 2.1%). The mean length of hospital stay was 16.8±8.8 days. Laboratory data within 3 days of admission demonstrated that the mean serum levels of PCT were 0.05±0.05 ng/mL (n=62) in the moderate group, 0.23±0.26 ng/mL (n=21) in the severe group and 0.44±0.54 ng/mL (n=12) in the critical group ( Figure 1A ). The total serum levels of procalcitonin increased as the disease worsened (P<0.05). Thirty-eight patients (32 discharged cases and 6 deaths) had serial procalcitonin values measured (within 3 days of admission, during the hospital stay, and within 7 days before hospital discharge) (Figure 1 B and D) . The results of the 32 discharged patients showed that the serum levels of procalcitonin decreased during recovery, and there was a significant difference between the levels within 3 days of admission and within 7 days before hospital discharge (Figure 1 B) . Among them, the procalcitonin levels of 14 patients were more than 0.1 ng/mL within 3 days of admission, which decreased significantly during recovery (Figure 1 C) . Interestingly, we found that most (5/6, 83 .3%) of the second PCT values measured in the death cases decreased slightly after the patients were admitted and received treatment. However, the third PCT values measured all increased significantly again (6/6, 100%) ( Figure 1D ). Then, it continuously increased as the disease worsened in the cases of death (P<0.05, Figure 1D ). The white blood cell count was normal in 66 cases (71%), decreased in 16 cases (17.2%), and increased in 11 cases (11.8%); the neutrophil count was decreased in 10 cases (11.5%) and increased in 19 cases 20.4%); other laboratory findings are shown in Table S2 . In addition, moderate patients, severe patients and critical patients were administered antiviral therapy, glucocorticoid therapy and oxygen therapy. Here, we report a total of 95 patients with laboratory-confirmed SARS-CoV-2 infection in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Sixty-two moderate patients, 21 severe patients and 12 critical patients were included in our study. Six (6.3%, all were critical patients) of the 95 patients in this cohort died. Procalcitonin, which is the 116-amino acid precursor of the hormone calcitonin, is normally synthesized and released by thyroid parafollicular C cells. However, it can also be synthesized in many extrathyroid tissues during bacterial infections, which is mediated by increased concentrations of tumor necrosis factor alpha and interleukin 6 [9] . Recently, several studies reported that evaluated PCT is positively associated with the severity of COVID-19 [3] [4] [5] [6] . A meta-analysis also demonstrated that procalcitonin values are related to an approximately 5-fold higher risk of severe SARS-CoV-2 infection [7] . Our study further classified severe infections into severe patients and critical patients. Our results showed that the mean serum levels of procalcitonin in severe patients were approximately 4 times higher than those in moderate patients, and they were approximately 8 times higher in critical Page 7 patients than in moderate patients. The PCT levels seemed to be severity-dependent and may be associated with bacterial coinfection, as the coinfection rate was close to the rate of procalcitonin increase in patients with moderate severity (approximately 10%). Notably, the coinfection rates were only 20% and 50% in severe and critical patients, but the rates of procalcitonin increase were 50% and 80%, respectively. In addition, a recent study hypothesized that the progressive increase in procalcitonin levels may predict a worse prognosis [10] . We included a total of 38 patients who had serially measured procalcitonin values. Thirty-two of them were discharged from the hospital, and 6 of them died. For the discharged patients, both high-normal procalcitonin levels and abnormal procalcitonin levels decreased during recovery. However, for the death cases, the serum levels of procalcitonin increased as the disease worsened. Our results showed that serial procalcitonin measurement can predict the prognosis of COVID-19 patients. In conclusion, our study demonstrates that PCT may be an indicator of severity and may contribute to determining the severity of patients infected with COVID-19. In addition, serial procalcitonin measurements may be useful in predicting prognosis. Additional investigation is needed to further illustrate the mechanisms by which increased PCT is synthesized and released in patients infected with COVID-19. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report -124 Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Clinical features of patients infected with 2019 novel coronavirus in Wuhan Clinical Characteristics of Coronavirus Disease 2019 in China Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis The notice of launching guideline on diagnosis and treatment of the novel coronavirus pneumonia Procalcitonin for diagnosing and monitoring bacterial infections: for or against Laboratory abnormalities in patients with COVID-2019 infection Procalcitonin values of patients infected with COVID-19. (A) Procalcitonin values of different type of patients infected with COVID-19, n=95, all quantification graphs represent mean ± SD and compared with analysis of variance (ANOVA) Serial procalcitonin measured value of patients infected with COVID-19, n=32 (high-normal and abnormal procalcitonin values), tested by Wilcoxon rank sum test. ****P < 0.0001;(C) Serial procalcitonin measured value of patients infected with COVID-19 from the cases of discharged patients (procalcitonin >0.1 ng/mL), n=14, tested by Wilcoxon rank sum test Serial procalcitonin measured value of patients infected with COVID-19 from the cases of the death, n=6, tested by Wilcoxon rank sum test The authors would like to thank the doctors, nurses, and medical students who helped with data collection.