Quantifying the clinical characteristics of coronavirus disease 2019 (COVID-19) of different age segments based on 60 patients

doi:10.21203/rs.3.rs-20112/v1

Download PDF

Research article

Quantifying the clinical characteristics of coronavirus disease 2019 (COVID-19) of different age segments based on 60 patients

https://doi.org/10.21203/rs.3.rs-20112/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this older preprint version

Read the latest preprint version →

Background: To observe the clinical characteristics of the novel coronavirus pneumonia of different age segments infected with novel coronavirus disease 2019 (COVID-19), to increase awareness of the clinical features of COVID-19, and improve diagnosis and treatment. Methods: By 15 February 2020, 60 patients diagnosed with COVID-19 had been admitted our hospital. We prospectively analyzed the clinical features of different age segments infected with COVID-19, including epidemiological, clinical, laboratory, and radiological characteristics, and treatment, clinical outcomes, and prognosis of this part of patients.

Results: We included 29 male and 31 female (median age = 46.18 years old (18–97). Fifty-five (91.7%) patients had a clear epidemiological contact history. The average incubation period is 7.92 days. The most common clinical manifestations are fever (85%) and cough (75). Peripheral white blood cell counts were mostly normal at admission, 7 days, and 14 days, with no difference in patients of different ages. The lymphocyte count was in the normal range on admission, but decreased after 7 days of disease treatment, especially in patients > 65 years old; the lymphocyte count increased again after 14 days. The lymphocyte count in >65-year-old patients was less than that in the <40 and 40–65 years old groups after 7 and 14 days, respectively. At admission, the CD4 T lymphocyte count was within the normal; however, after 14 days the CD4 T lymphocyte count was 723.46 ± 243.82/ml, 640.00 ± 242.30/ml, and 399.88 ± 256.16/ml in the three age segments, respectively. The > 65 years old group had higher levels of lactate dehydrogenase (269.83 ± 73.36 vs. 208.52 ± 35.67 and 243.83 ± 76.66) after 14 days. Imaging revealed more lesions in the 40–65 and > 65 years old groups. The days after the nucleic acid detection turned negative in the three age groups were : 9.19 ± 3.93 (<40), 10.04 ± 4.10 (40–65), and 13.57 ± 2.76 (>65).

Conclusion: Patients with COVID-19 pneumonia generally had an epidemiological history. Older patients showed more extensive lesions upon admission, more severe illness, slower recovery of immune function, the longer viral nucleic acid persistence.

Infectious Diseases

coronavirus disease 2019

COVID-19

clinical characteristics

lung

age

Recently, a novel coronavirus has emerged from Wuhan, a city in central China that has an estimated population of about 10 million and is a major transportation hub. Within a few weeks, the novel coronavirus, tentatively named as coronavirus disease 2019 (COVID-19), was announced by the World Health Organization ^[1]. Unfortunately, COVID-19 threatens not only China, but also has spread internationally through travelers. Coronavirus is a large family of RNA viruses that can be transmitted through droplets or contact, and may also be transmitted through the fecal-oral route, with a high incidence and rapid infection, posing a huge threat to global public health ^[2]. Nanjing is also a high-incidence city, and our hospital (Nanjing Public Health Medical Center (Jiangsu Provincial Infectious Diseases Hospital)), is a designated site for provincial infectious diseases, which has shouldered the heavy responsibility of treating such patients. Up to 10 January 2020, 60 patients diagnosed with COVID-19 had been admitted our hospital. In the present study, we prospectively collected and analyzed the epidemiological, clinical, laboratory, and radiological characteristics, and the treatment and clinical outcomes of these patients. We also stratified these data according three patient age groups (< 40 years old, 40–65 years old, and > 65 years old) to increase awareness of the clinical features of COVID-19, and to improve the diagnosis and treatment of patients.

Patients and parameters

Up to 10 January 2020, 60 patients diagnosed with COVID-19 infection were collected. We prospectively collected and analyzed the epidemiological, clinical, laboratory, and radiological characteristics, and the treatment and clinical outcomes of three patient age groups (< 40 years old, 40–65 years old, and > 65 years old) and summarized their clinical characteristics and prognosis.Ethics approval and consent to participate written consent was exempted by the institutional review boards of the Second Hospital of Nanjing as all case-based data utilized in the study are routinely collected. All data were fully anonymized before analysis. These patients have not been reported in any other submission by our team or anyone else before.

Statistical Analysis

Classification variables are expressed as frequencies or percentages. For normally distributed data, measurements were expressed as the mean ± SD, and significance is detected using the chi squared or Fisher’s exact test. The quantified variables of parameters are expressed as mean ± SD, and the significance was tested using a t-test. P < 0.05 was considered statistically significant in all statistical analyses. SPSS statistical software (Macintosh version 26.0, IBM, Armonk, NY, USA) were used for the statistical analysis.

The 60 patients were diagnosed with COVID-19 infection using real-time reverse transcription (RT)-PCR and were admitted to our hospital. All patients satisfied the probable fifth edition COVID-19 criteria recommended by the World Health Organization. The study included 29 male and 31 female patients, whose median age was 46.18 (range: 18–97) years old. Forty (66.67%) of these patients had no underlying disease. The other 20 patients had underlying disease: Eight suffered from diabetes, six suffered from chronic obstructive pulmonary disease (COPD), and six suffered from hypertension. Fifty-five (91.7%) patients had a clear epidemiological contact history, including a recent trip to Wuhan and close contact with patients with pneumonia, which included 36 patients in 6 family clusters. The average incubation period was 7.92 days. The most common clinical manifestations were fever (85%) and cough (75%), followed by chest tightness (36.7%) and sore throat (33.3%). The laboratory test results showed that the peripheral white blood cell counts were mostly normal at admission, 7 days, and 14 days, with no difference in patients of different ages. The lymphocyte count was within the normal range on admission, but decreased after 7 days of treatment, with a significant decline(p = 0.0292)in 65 years old group. The lymphocyte count increased again after 14 days of treatment; however, but the lymphocyte count in the 65 years old group was less than that in the < 40 years old and 40–65 years old groups after 7 and 14 days of treatments, respectively. The total CD4 T lymphocyte count was in the normal range on admission and after 14 days of treatment; however, in the older patients group (> 65 years old), the CD4 T lymphocyte count was significantly lower than that in the young and middle-aged patients (723.46 ± 243.82, 640.00 ± 242.30, 399.88 ± 256.16/ml) in the < 40

years old, 40–65 years old, and > 65 years old groups, respectively). Patients aged > 65 years old had higher levels of lactate dehydrogenase (LDH)(269.83 ± 73.36 vs. 208.52 ± 35.67 and 243.83 ± 76.66 in the other two groups) after 14 days of treatments. Arterial blood gas analysis showed lower scores among the 40–65 years old and the > 65 years old groups than in the < 40 years old group. The imaging distribution on admission showed more lesions in the 40–65 years old and < 65 years old groups compared with those in the < 40 years old group. The overall number of days until nucleic acid detection turned negative was 10.11 days: 9.19 ± 3.93 (< 40 years old), 10.04 ± 4.10 (40–65 years old), and 13.57 ± 2.76 (< 65 years old). The overall clinical manifestation and laboratory results of the patients are described in Table 1.

Table 1

Baseline characteristics, laboratory findings, imaging features, and the progress of patients with COVID-19 in different age segments.
Groups	Cotends	All patients (n = 60)	40 years olds	40–65 years olds	65 years olds	p
Sex	..	Male 29,Female 31	14(51.85)	12(48.00)	3(37.76)	0.8778
Symptoms -No./total No. (%)	Fever	51༏60(85.0)	19(73.08)	23(92.00)	8(100.00)	0.1092
	Cough	45༏60(75.0)	16(61.54)	22(88.00)	7(87.50)	0.0616
	Chest tightness	22༏60(36.7)	4(15.38)	14(56.00)	4(50.00)	0.0181
	Sore throat	20༏60(33.3)	10(38.46)	9(36.00)	1(12.50)	0.3818
Incubation period	..	7.92days	7.82 ± 3.29	7.74 ± 3.08	9.00 ± 3.94	0.7272
Leukocyte(× 10⁹/L)(range 3.69–9.16༉	Before treatment	4.48 ± 1.41	4.52 ± 1.34	4.34 ± 1.66	4.78 ± 0.72	0.7432
	After 7 days of treatment	4.18 ± 1.40	4.29 ± 1.39	4.21 ± 1.51	3.74 ± 1.16	0.6221
	After 14 days of treatment	5.70 ± 2.45	4.99 ± 1.51	6.30 ± 3.02	6.10 ± 2.69	0.1447
Lymphocyte(× 10⁹/L)(range 0.80-4.00༉	Before treatment	1.34 ± 0.59	1.50 ± 0.45	1.26 ± 0.71	1.06 ± 0.44	0.1228
	After 7 days of treatment	1.14 ± 0.52	1.31 ± 0.48	1.08 ± 0.56	0.78 ± 0.28	0.0292
	After 14 days of treatment	1.48 ± 0.51	1.65 ± 0.34	1.47 ± 0.59	0.97 ± 0.37	0.0029
CD4(༏ul)༈range 414–1123༉	Before treatment	537.34 ± 312.16	611.23 ± 308.61	513.40 ± 322.38	372.00 ± 239.42	0.1463
CD4(༏ul)༈range 414–1123༉	After 14 days of treatment	644.29 ± 262.82	723.46 ± 243.82	640.00 ± 242.30	399.88 ± 256.16	0.0075
LDH	Before treatment	247.90 ± 89.46	233.77 ± 81.03	251.56 ± 91.14	282.38 ± 110.65	0.3978
	After 7 days of treatment	256.56 ± 79.50	235.00 ± 44.44	262.37 ± 97.89	296.00 ± 78.03	0.2001
	After 14 days of treatment	231.45 ± 64.25	208.52 ± 35.67	243.83 ± 76.66	269.83 ± 73.36	0.0496
PaO2	Before treatment	105.41 ± 34.58	127.58 ± 46.21	98.11 ± 22.48	86.14 ± 15.94	0.0198
	After 7 days of treatment	88.08 ± 26.01	126.75 ± 38.91	83.23 ± 12.63	75.00 ± 16.41	0.0148
	After 14 days of treatment	95.95 ± 33.37	138.00 ± 43.55	93.36 ± 22.03	79.67 ± 33.28	0.0335
Number of affected lobes on admission	1–2 lung fields	19/60(31.7)	15(78.9)	4/60(21.1)	0(0)	< 0.0001
	2–4 lung fields	21/60(35.0)	10(47.6)	11/60(53.4)	0(0)
	4–6 lung fields	20/60(33.3)	2(10.0)	10(50.0)	8(100.00)
Days of the nucleic acid detection turned negative	..	10.11	9.19 ± 3.93	10.04 ± 4.10	13.57 ± 2.76	0.0373

In the present study, we report the analysis of a cohort of 60 patients with laboratoryconfirmed COVID-19 infection. There were no differences between the male and female patients. Fever was the most common symptom (85%), followed by cough without sputum, chest tightness, and sore throat, which were consistent with current reports concerning COVID-19 pneumonia ^[2–4]. These clinical features are similar to other respiratory infections, making it difficult to identify COVID-19 because most patients presented with upper respiratory tract signs and symptoms, such as fever, dry cough, and dyspnea. Most patients (55 (91.7%)) had a clear epidemiological contact history, including recent travel to Wuhan or close contact patients with COVID-19 infection. Among these patients, which included 36 patients in 6 family clusters, most manifested as one confirmed patient in the family, with others being diagnosed subsequently, including some asymptomatic patients. This showed strong disease infectiousness.

and the importance of isolation ^[5]. Most patients had no underlying disease, suggesting no significant correlation between this disease and the patient’s underlying disease. Older patients had longer incubations periods and tended to develop more severe disease, indicating that the older the patients, the worse their condition becomes. Analysis of the peripheral white blood cell counts indicated that white blood cells have no obvious involvement in, or correlation with, the immune process of the disease; however, it is also possible that the patients in this group are all imported patients with relatively mild illness ^[6]. Earlier studies have shown that lymphopenia is a typical laboratory abnormality observed during highly pathogenic coronavirus infections, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) infections^[7], and is believed to be associated with disease severity. Recent studies have also reported decreases in the lymphocyte counts in the peripheral blood and increases in serum inflammatory cytokine levels in COVID-19 patients. Other reports showed that the degree of CD4 T lymphopenia is higher in patients with severe COVID-19 disease than in mild cases, and is associated with disease severity ^[7–9]. The CD4 T lymphocyte count was significantly lower in elderly patients than in middle-aged and young patients, which might be related to the virus attacking the target organ at the early stage, whereas in the later period, it starts to attack the body's immune system and causes to T lymphocyte apoptosis or bone marrow suppression, which is more obvious in middle-aged and elderly patients ^[10–12].

Chest high-resolution computed tomography (HRCT) is an important screening tool for COVID-19 because of its high sensitivity and convenience. The imaging manifestations of the new coronavirus pneumonia are similar to those of common viral pneumonia, but also have their own imaging characteristics. The most common manifestations of new coronavirus pneumonia in the early stage are patchy ground glass opacities, mainly distributed in the sub-pleural area ^[13–15]. At disease onset, the number of affected lobes on admission in elderly patients was higher (Fig. 1a–b), and the disease progressed faster than it did in young patients after 7 days of treatment (Fig. 1c–d). In our study, the lesions mainly involved 1–2 lung fields and 2–4 lung fields, with a higher number of lesions in the lungs of older patients.

COVID-19 could be considered as a distinct coronavirus from SARS, which was probably transmitted from bats or another host after developing the ability to infect humans ^[16]. The genome of COVID-19 has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV ^{[17, 18]}. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral, and vaccination strategies for this emerging infection. The sequence of 2019 nCoV receptor binding domain (RBD), including its receptor-binding motif (RBM) that directly contacts angiotensin I converting enzyme 2 (ACE2), is similar to that of SARS-CoV, strongly suggesting that COVID-19 uses ACE2 as its receptor ^[19]. Recently, this disease has been employed as an anti-HIV treatment and has been combined with interferon to treat disease. Most patients with COVID-19 in our hospital received Abidol or Lopinavir antiviral therapy or intravenous methylprednisolone in some severe patients. In our study, the average number of days after the nucleic acid detection turned negative after treatment was 10.11, with the oldest patients taking the longest to test negative for viral nucleic acids. However, the number days of nucleic acid turn egative in older patients was significantly longer than that in the middle-aged and young patients (10.04 ± 4.10, 9.19 ± 3.93). Indicating that the older the patient, the longer the treatment cycle.

The purpose of this study was to observe the clinical characteristics of the novel coronavirus pneumonia and to participate in controlling the outbreak by effective countermeasures. This analysis has limitations. First, this clinical research involved a relatively small number of cases. Second, the data analyzed in this study were from the early phase of the outbreak and we lack follow-up data on long-term prognosis and complications. Next, our team will continue to follow up these patients in terms of their prognosis and long-term complications.

The patents with coronavirus disease 2019 pneumonia in this study generally had an epidemiological history. The most common clinical manifestations are fever and cough without sputum. Older patients had more extensive the lesions upon admission, a higher proportion of severe illness, slower recovery of immune function, and a longer number of days nucleic acid turn egative after treatment .

COVID-19: coronavirus disease 2019; COPD: chronic obstructive pulmonary disease; LDH: lactate dehydrogenase; SARS-CoV: severe acute respiratory syndrome coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; HRCT: high-resolution computed tomography ;RBD: receptor binding domain; RBM: receptor-binding motif; ACE2: angiotensin I converting enzyme 2

Acknowledgements

Not applicable.

Authors’ contributions

WWG conducted the literature review and wrote the draft. YZ and YXY conceived the study and revised the manuscript. All authors have read and approved the manuscript.

Funding

The authors received no specific funding for this work.

Ethics approval and consent to participate

Ethics approval and consent to participate written consent was exempted by the institutional review boards of the Second Hospital of Nanjing as all case-based data utilized in the study are routinely collected. All data were fully anonymized before analysis.

Consent to publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

Data relating to this study are contained and presented in this document. Other materials are available from the corresponding authors on reasonable request.

Authors' Information

Wei-Wei Gao, Department of Tuberculosis, Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China, Physician, Email: [email protected], Mobile Number: 15251856076.

Yi Zeng, Department of Tuberculosis, Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China, Master, Chief Physician, Email: [email protected].Mobile Number: 13601586598.

Zhiliang Hu,Department of infectious Disease ,Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Doctor,AssociateChief Physician, Email:[email protected].

Yun Chi,Department of infectious Disease ,Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Master，Chief Physician,Email:[email protected].

Yishan Zheng,Department of Intensive Medicine,Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Doctor,Chief Physician,Email:[email protected].

Chunmei Hu,Department of Tuberculosis, Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Doctor,AssociateChief Physician,Email:[email protected].

Yongxiang Yi,Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Doctor,AssociateChief Physician,[email protected].

Xia Zhang,University of Chinese Medicine, The Second Hospital of Nanjing, Nanjing Municipal Public Health Medical Center, Nanjing, Jiangsu 210003, P.R. China,Chief Physician,Email:[email protected].

World Health Organization. Situation report-23, Novel Coronavirus（COVID-19）, 12 February, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.
Zhang MQ, Wang XH, Chen YL, et al. Clinical features of coronavirus disease 2019 pneumonia in the early stage from a fever clinic in Beijing.[J].Zhonghua Jie He He Hu Xi Za Zhi; 2020; 43(0): p. 013.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with coronavirus disease 2019 in Wuhan, China: Lancet. 2020; S0140-6736(20)30183-5.
N Chen, M Zhou, X Dong, et al. Epidemiological and clinical characteristics of 99 cases of coronavirus disease 2019 pneumonia in Wuhan, China: a descriptive study. [published online ahead of print, 2020 Jan 29]. Lancet.
Huang R, Xia J, Chen Y, et al. A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China: [J]. Lancet Infect Dis; 2020. doi: 10.1016/S1473_3099(20)30147_X.
Li YX, Wu W, Yang T, et al. Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19[J]. Zhonghua Nei Ke Za Zhi; 2020. 59(0):e003.
Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients[J]. medRxiv, 2020.
Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With coronavirus disease 2019-Infected Pneumonia in Wuhan, China. JAMA; 2020. 2020-02-07.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of coronavirus disease 2019 pneumonia in Wuhan, China: a descriptive study. LANCET; 2020.2020-01-30.
Chen J, Subbarao K, The Immunobiology of SARS [J]. Annu Rev Immunol.2007;25:443-72.
Bermejo-Martin JF, Almansa R, Menéndez R, et al. Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection: Lymphopenia in severe COVID-19 infection[J]. J Infect.2020;doi: 10.1016/j.jinf.2020.02.029.
Torres A, Ceccato A, Ferrer M, et al. Effect of Corticosteroids on C-Reactive Protein in Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response: The Effect of Lymphopenia [J]. J Clin Med.2019;8(9):doi：10.3390/jcm8091461.
Pan Y, Guan H, Zhou S, et al. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (COVID-19): a study of 63 patients in Wuhan, China[J]. Eur Radiol.2020; https://doi.org/10.1007/s00330-020-06731-x.
Zhou S, Wang Y, Zhu T, et al. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China[J]. AJR Am J Roentgenol.2020; 1-8，doi: 10.2214/AJR.20.22975.
Wu J, Wu X, Zeng W, et al. Chest CT Findings in Patients with Corona Virus Disease 2019 and its Relationship with Clinical Features[J]. Invest Radiol.2020;doi：10.1097/RLI.0000000000000670.
Benvenuto D, Giovannetti M, Ciccozzi A, et al. The 2019-new coronavirus epidemic: evidence for virus evolution[J]. J Med Virol.2020.
Jasper FC, Kin HK, Zheng Z, et al. Genomic characterization of the 2019 novel humanpathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes & Infections. 2020; 9:1, 221-236, doi: 10.1080/22221751.2020.1719902.
Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 2020; https://doi.org/10.1002/jmv.25681.
Wan Y, Shang J, Graham R, et al. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS[J]. J Virol.2020.

Download PDF

Version 1

posted

You are reading this older preprint version

Read the latest preprint version →

Quantifying the clinical characteristics of coronavirus disease 2019 (COVID-19) of different age segments based on 60 patients

Status:

Version 1

Abstract

Figures

Background

Methods

Patients and parameters

Statistical Analysis

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Status:

Version 1