Lupine Publishers | Current Trends on Biotechnology & Microbiology
Abstract
This article discusses the value research data in Guan’s
paper published on medRxiv, February 9, 2020. In terms of experimental data,
the preprinted paper is by far the largest sample number of 2019-new
coronavirus (SARS-CoV-2) infected patients. Including 552 hospitals from 31
provinces in China as of January 29, 2020, a total of 1,099 cases. Laboratory
evaluations include multiple blood cell counts, blood chemistry, coagulation
tests, liver and kidney function, electrolytes, C-reactive protein,
Keywords: Reference range; 2019-nCoV, SARS-CoV-2, 2019-nCoV
ARD, COVID-19
Introduction
Professor Guan et al. [1] recently published an article
“clinical characteristics of 2019 novel coronavirus infection in china”. It is
a preprinted version of medRxiv on BMJ publishing platform. The authors of the
article covered all frontline anti-epidemic frontlines including Guangzhou
Institute of Respiratory Disease, Wuhan Jinyintan Hospital, Institute of
Hematology, Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology, The Central Hospital of Wuhan, Huanggang Central
Hospital, Department of Medicine and Therapeutics, et al. The Chinese
University of Hong Kong. In this retrospective study, the authors extracted the
data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD (COVID-19) from
552 hospitals in 31 provinces/ provincial municipalities through January 29th,
2020. So far, it is the largest number of cases collected, the clinical
characteristics of the patients with the most complete distribution, and the
most comprehensive Chinese experience of SARS-CoV-2 treatment are released to
the world.
In the preprinted paper, the authors found that fever
occurred in only 43.8% of patients with 2019-nCoV ARD (COVID-19) but developed
in 87.9% following hospitalization. Demographic data showed a median age of
47.0 years (IQR, 35.0-58.0 years). 2.09% were healthcare workers. The median
incubation period was 3.0 days (range, 0 to24.0). Patients who underwent chest
computed tomography on admission, 76.4% manifested as pneumonia. There are
normal radiological manifestations in some infected patients. In addition, the
researchers obtained a series of laboratory findings, such as 82.1% and 36.2%
of patients had lymphopenia and thrombocytopenia, respectively. Overall,
leukopenia was observed in 33.7% of patients. Most patients demonstrated
elevated levels of C-reactive protein, rare increases in D-dimer levels, and so
on. The standards used by the authors in analyzing laboratory data do not meet
the standards of the People’s Republic of China’s health industry (WS/T
405-2012). We will take this article “Clinical Characteristics of New
Coronavirus Infections in China 2019”as an example to explore the reference
scope of laboratory test.
Methods and Results
The report delineated 1,099 patients with 2019-nCoV ARD
(COVID-19) from 552 hospitals in 31 provinces/province-level municipalities.
Cases were diagnosed based on the WHO interim guidance [2]. Patients were
classified into severe and non-serious 2019-nCoV ARD (COVID-19) based on the
guideline of the American Thoracic Society and Infectious Disease Society of
America [3]. Radiologic and laboratory findings was also based on the grouping
of severe and non-severe case patients. Table 1 showed lymphopenia was observed
in 82.1% of patients on admission (79.3% in nonsevere cases; 95.5% in severe
cases), and thrombocytopenia in 36.2% (31.6% in non-severe cases; severe cases
57.7%). Overall, leukopenia was observed in 33.7% of patients (28.1% in
nonsevere cases; 61.1% in severe cases).
Hemoglobin (Hb) showed almost no significant decrease. There
are significant differences of Hb level between non-serious cases and severe
cases. It should be noted that only 978 of the 1099 cases provided complete
blood routine test data, while the data of absolute value of lymphocytes and
platelet counts were less than 978 cases. This indicating that there is no
uniform requirement for the integrity of test data.
Most patients (60.7%) demonstrated elevated levels of
C-reactive protein levels (56.4% in non-severe cases; 81.5% in severe cases),
rare increases in alanine aminotransferase, aspartate aminotransferase,
creatine kinase, and D-dimer. The authors only provided 560 cases of the
D-dimer detection value, in which 46.4% patients manifest the increase tendency
(43.2% in non-severe cases; 59.6% in severe cases). Severe cases had more
prominent laboratory abnormalities (i.e., leukopenia, lymphopenia, thrombocytopenia,
elevated C-reactive protein levels) as compared with non-severe cases (all
P<0.05).
Discussion
In terms of experimental data, the preprinted paper is by
far the largest sample number of 2019-new coronavirus (SARS-CoV-2) infected
patients. We noticed that the author analyzed laboratory data, especially blood
routine test data, and reached conclusions such as leukopenia, lymphopenia,
thrombocytopenia, and elevated C-reactive protein in COVID-19 patients
according to certain criteria, which is not conform to the standards of the
People’s Republic of China’s health industry document WS/T405-2012.
For example, the leukopenia defined in the article is based
on less than 4.0×109/L; the lymphocyte reduction is based on less than
1.5×109/L; the thrombocytopenia is based on less than 150×109/L; and the
C-reactive protein level is based on be equal or greater than 10mg/L was
abnormal (Table 1).
Lupinepublishers-openaccess-Agriculture
Plus-minus values are means ± SD. Lymphopenia denoted the
lymphocyte count of less than 1,500 per cubic millimeter. Thrombocytopenia
denoted the platelet count of less than 150,000 per cubic millimeter. PaO2:FiO2
was defined as the ratio of the partial pressure of arterial oxygen to the
fraction of inspired oxygen.
P values denoted the comparison between mild-moderate cases
and severe cases.
As for D-dimer, the author took greater than or be equal
0.5mg/L as the standard for abnormal. However, the different hospitals in
China, the difference in methods and reagents used, it is generally considered
that the reference interval is less than 0.3mg/L or less than 0.5mg/L. The
article uniformly took be equal or greater than 0.5mg/L as the standard for abnormal
elevation. Obviously, the 552 hospitals as the participating units are unlikely
to use exactly the same methods and reagents.
Lupinepublishers-openaccess-Agriculture
The China national industry standard blood routine test
reference range was released in 2012, and it has been nearly eight years. The
following table lists the reference range for the analysis of venous blood in
the Chinese adult population for instrumental detection methods (Table 2).The
preprinted article did not adopt this health industry standard, which shows
that the criterion has not been accepted and recognized by Chinese clinicians.
It is a very important topic whether national industry standards, especially
reference ranges, are recognized by the majority of Chinese clinicians.
Reference range is the basis for clinicians diagnosing diseases.
In view of the fact that the research object is Chinese, we
suggest that researchers should try to adopt the domestic recommended standards
instead of using the previous concepts and foreign standards. If domestic
industry standards are used in this article, their statistical results and
proportions may be quite different. In particular, the absolute value of lymphocytes
should be significantly different, which may lead to large differences in
conclusions. As we all know, the new coronavirus epidemic recently occurred in
Wuhan city, Hubei Province, China has spread to other parts of China and
abroad. As an acute respiratory infectious disease, the disease has been
included in the Class B infectious diseases stipulated in the Law of the
People’s Republic of China on the Prevention and Control of Infectious Diseases
and is managed as a Class A infectious disease. The National Health Committee
of the People’s Republic of China has continuously revised the “Diagnosis and
Treatment Program for Pneumonia of New Coronavirus Infection”, which is
currently in its fifth edition on a trial basis. The guidelines point out that
the diagnosis of suspected cases of COVID-19 should be combined with a
comprehensive analysis of epidemiological history and clinical manifestations.
The clinical manifestations include
1. Fever and / or respiratory symptoms
2. The imaging characteristics of pneumonia described above
(abbreviated in this article)
3. The total number of white blood cells is normal or
decreased in the early stage of onset, or the lymphocyte count is decreased.
Any case with epidemiological history that meets any two of
the clinical manifestations can be determined as a suspected case. Once a
misdiagnosis occurs due to a misjudgment of the reference value range, it is
likely to cause severe unforeseen consequences.
The biochemical test results involved in the preprint
version of the article also did not adopt domestic standards, and the
determination of many biochemical indicators is also related to gender, which
are issues that clinicians should pay attention to. If the author team includes
medical laboratory experts, I believe that the aforementioned laboratory data
and reference ranges, and methodological flaw may be avoided. As stated by the
authors, some cases had incomplete documentation of the exposure history,
symptoms and laboratory testing given the variation in the structure of
electronic database among different participating site and the urgent timeline
for data extraction. Some cases were diagnosed in out-patient settings where
medical information was briefly documented, and incomplete laboratory testing
was applied.
On the other hand, in clinical laboratory practice, we
recommend that laboratory technician communicate with clinicians to
scientifically explain the clinical significance and reference range of
laboratory data. Only in this way, a new reference range can be adopted and
applicated in the hospital. Secondly, whether it is fully adopted or partially
adopted, it depends on how technicians connect closely with the clinician and
perform corresponding verification. The national industry standard is only a
recommended standard, not a mandatory standard. Clinicians are generally
rigorous when selecting a standard for disease diagnosis. The preprint article
illustrates exactly this problem. When clinicians judge the test data, they
have not adopted our health industry standards as the judgment standard. It is
a typical example of the disconnection between laboratory and clinical. This is
a problem worthy of laboratory physician’s reflection and deep thought.
For more Lupine Publishers
Current Trends on Biotechnology & Microbiology Journal Articles:
https://lupine-biotechnology-microbiology.blogspot.com
