I. Personalized, Collaborative and Multidisciplinary Management
FAHZU is a designated hospital for COVID-19 patients, especially severe and critically ill individuals
whose condition changes rapidly, often with multiple organs infected and requiring the support
from the multidisciplinary team (MDT). Since the outbreak, FAHZU established an expert team
composed of doctors from the Departments of Infectious Diseases, Respiratory Medicine, ICU,
Laboratory Medicine, Radiology, Ultrasound, Pharmacy, Traditional Chinese Medicine, Psychology,
Respiratory Therapy, Rehabilitation, Nutrition, Nursing, etc. A comprehensive multidisciplinary
diagnosis and treatment mechanism has been established in which doctors both inside and outside
the isolation wards can discuss patients'conditions every day via video conference. This allows for
them to determine scientific, integrated and customized treatment strategies for every severe and
critically ill patient.
Sound decision-making is the key to MDT discussion. During the discussion, experts from different
departments focus on issues from their specialized fields as well as critical issues to diagnoses and
treatment. The final treatment solution is determined by experienced experts through various
discussions of different opinions and advice.
Systematic analysis is at the core of MDT discussion. Elderly patients with underlying health
conditions are prone to becoming critically ill. While closely monitoring the progression of COVID-19,
the patient's basic status, complications and daily examination results should be analyzed
comprehensively to see how the disease will progress. It is necessary to intervene in advance to stop
the disease from deteriorating and to take proactive measures such as antivirals, oxygen therapy,
and nutritional support.
The goal of MDT discussion is to achieve personalized treatment. The treatment plan should be
adjusted to each person when considering the differences among individuals, courses of disease,
and patient types.
Our experience is that MDT collaboration can greatly improve the effectiveness of the diagnosis and
treatment of COVID-19.
II. Etiology and Inflammation Indicators
Detection of SARS-CoV-2 Nucleic Acid
1.1 Specimen Collection
Appropriate specimens, collection methodds and collection timing are important to
improve detection sensitivity. Specimen types include: upper airway specimens
(pharyngeal swabs, nasal swabs, nasopharyngeal secretions), lower airway specimens
(sputum, airway secretions, bronchoalveolar lavage fluid), blood, feces, urine and
conjunctiva[ secretions. Sputum and other lower respiratory tract specimens have a
high positive rate of nucleic acids and should be collected preferentially. SARS-CoV-2
preferentially proliferates in type II alveolar cells (AT2) and peak of viral shedding
appears 3 to 5 days after the onset of disease. Therefore, if the nucleic acid test is
negative at the beginning, samples should continue to be collected and tested on
subsequent days.
1.2 Nucleic Acid Detection
Nucleic acid testing is the preferred method for diagnosing SARS-CoV-2 infection. The
testing process according to the kit instructions is as follows: Specimens are
pre-processed, and the virus is lysed to extract nucleic acids. The three specific genes of
SARS-CoV-2, namely the Open Reading Frame la/b (ORFla/b), nucleocapsid protein
(N), and envelope protein (E) genes, are then amplified by real-time quantitative PCR
technology. The amplified genes are detected by fluorescence intensity. Criteria of
positive nucleic acid results are: ORFla/b gene is positive, and/or N gene/E gene are
positive.
The combined detection of nucleic acids from multiple types of specimens can improve
the diagnostic accuracy. Among patients with confirmed positive nucleic acid in
respiratory tract, about 30% - 40% of these patients have detected viral nucleic acid in
the blood and about 50% - 60% of patients have detected viral nucleic acid in feces.
However, the positive rate of nucleic acid testing in urine samples is quite low.
Combined testing with specimens from respiratory tract, feces, blood and other types of
specimens is helpful for improving the diagnostic sensitivity of suspected cases,
monitoring treatment efficacy and the management of post-discharge isolation
measures.
f)
Virus Isolation and Culture
Virus culture must be performed in a laboratory with qualified Biosafety Level 3 (BSL-3).
The process is briefly described as follows: Fresh samples of the patient's sputum,
feces, etc. are obtained and inoculated on Vero-E6 cells for virus culture. The cytopathic
effect (CPE) is observed after 96 hours. Detection of viral nucleic acid in the culture
medium indicates a successful culture. Virus titer measurement: After diluting the virus
stock concentration by a factor of 10 in series, the TCIDS0 is determined by the
micro-cytopathic method. Otherwise, viral viability is determined by plaque forming
unit (PFU).
E) Detection of Serum Antibody
Specific antibodies are produced after SARS-CoV-2 infection. Serum antibody
determination methods include colloidal gold immunochromatography, ELISA,
chemiluminescence immunoassay, etc. Positive serum-specific lgM, or specific lgG
antibody titer in the recovery phase ~4 times higher than that in the acute phase, can be
used as diagnostic criteria for suspected patients with negative nucleic acid detection.
During follow-up monitoring, lgM is detectable 10 days after symptom onset and lgG is
detectable 12 days after symptom onset. The viral load gradually decreases with the
increase of serum antibody levels.
C,
Detecting Indicators of Inflammatory Response
It is recommended to conduct tests of (-reactive protein, procalcitonin, ferritin,
•-dimer, total and subpopulations of lymphocytes, IL-4, IL-6, IL-10, TNF-a, INF-y and
other indicators of inflammation and immune status, which can help evaluate clinical
progress, alert severe and critical tendencies, and provide a basis for the formulation of
treatment strategies.
Most patients with C0VID-19 have a normal level of procalcitonin with significantly
increased levels of (-reactive protein. A rapid and significantly elevated (-reactive
protein level indicates a possibility of secondary infection. •-dimer levels are
significantly elevated in severe cases, which is a potential risk factor for poor prognosis.
Patients with a low total number of lymphocytes at the beginning of the disease
generally have a poor prognosis. Severe patients have a progressively decreased
number of peripheral blood lymphocytes. The expression levels of IL-6 and IL-10 in
severe patients are increased greatly. Monitoring the levels of IL-6 and IL-10 is helpful to
assess the risk of progression to a severe condition.
O Detection of Secondary Bacterial or Fungal Infections
Severe and critically ill patients are vulnerable to secondary bacterial or fungal
infections. Qualified specimens should be collected from the infection site for bacterial
or fungal culture. If secondary lung infection is suspected, sputum coughed from deep
in the lungs, tracheal aspirates, bronchoalveolar lavage fluid, and brush specimens
should be collected for culture. Timely blood culture should be performed in patients
with high fever. Blood cultures drawn from peripheral venous or catheters should be
performed in patients with suspected sepsis who had an indwelling catheter. It is
recommended that they take blood G test and GM test at least twice a week in addition
to fungal culture.
0
Laboratory Safety
Biosafety protective measures should be determined based on different risk levels of
experimental process. Personal protection should be taken in accordance with BSL-3
laboratory protection requirements for respiratory tract specimen collection, nucleic
acid detection and virus culture operations. Personal protection in accordance with
BSL-2 laboratory protection requirement should be carried out for biochemical,
immunological tests and other routine laboratory tests. Specimens should be
transported in special transport tanks and boxes that meet biosafety requirements. All
laboratory waste should be strictly autoclaved.
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