The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.
Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; immunology ; pathogenicity ; Coronavirus Infections ; diagnosis ; prevention & control ; therapy ; virology ; Humans ; Middle East Respiratory Syndrome Coronavirus ; drug effects ; immunology ; pathogenicity ; Pandemics ; prevention & control ; Pneumonia, Viral ; diagnosis ; prevention & control ; therapy ; virology ; SARS Virus ; drug effects ; immunology ; pathogenicity ; Severe Acute Respiratory Syndrome ; diagnosis ; prevention & control ; therapy ; virology ; Viral Vaccines

Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.
Antibodies, Viral/*immunology ; Blotting, Western ; Coronavirus 229E, Human/*immunology ; Coronavirus OC43, Human/*immunology ; Cross Reactions ; Humans ; Nucleocapsid Proteins/genetics/*immunology ; Recombinant Proteins/immunology ; SARS Virus/genetics/*immunology ; Severe Acute Respiratory Syndrome/diagnosis/*immunology

Adult ; Antibodies, Viral ; blood ; China ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS Virus ; immunology ; isolation & purification ; Severe Acute Respiratory Syndrome ; blood ; diagnosis ; virology ; Time Factors

OBJECTIVETo identify patients with SARS coronavirus infection who have only mild symptoms.

METHODEnzyme-linked immunosorbent assay was employed to detect serum antibody against SARS coronavirus in the lysate of whole SARS coronavirus from 19 SARS patients and 200 medical staff members without obvious SARS symptoms after possible exposure to the virus during routine medical practice.

RESULTSSerum IgG antibody against SARS coronavirus was detected in all the 19 SARS patients, and among the 200 staff members, 20 (10%) were found positive for the antibody but with no obvious or only mild symptoms.

CONCLUSIONSerum IgG antibody against SARS coronavirus is positive in a small proportion (around 10%) of the medical staff members exposed to the virus in our hospital, but may not cause obvious symptoms, suggesting SARS coronavirus infection might in some cases have mild or even no clinical manifestations.

Adult ; Antibodies, Viral ; blood ; Female ; Humans ; Immunoglobulin G ; blood ; Infectious Disease Transmission, Patient-to-Professional ; Male ; Medical Staff, Hospital ; SARS Virus ; immunology ; isolation & purification ; Severe Acute Respiratory Syndrome ; diagnosis ; immunology ; transmission

INTRODUCTIONSingapore was one of 29 countries worldwide affected by severe acute respiratory syndrome (SARS) in 2003.

MATERIALS AND METHODSThere were 238 cases identified during the outbreak. We performed a retrospective analysis of the clinical and laboratory data of 234 patients admitted to Tan Tock Seng Hospital and Singapore General Hospital.

RESULTSThe mean age of patients was 21 years, 31.6% of patients were males and 41.8% were healthcare workers. At presentation, the common symptoms were fever, myalgia, cough and headache; rhinorrhoea was uncommon. On admission, 21% had leukopenia, 18% had thrombocytopaenia, 29% had hyponatraemia, 31% had hypokalaemia, 21% had transaminitis. Polymerase chain reaction (PCR) testing of respiratory and stool samples provided the best yield at the end of the first week of illness. Thirty-two patients were initially not recognised as probable SARS and were reclassified when the serology test results were available. The chief reasons for not identifying these patients early were persistently normal chest X-rays (68.8%), very mild presentation (43.8%) and the presence of a concomitant illness (12.5%). Overall, 12% of the patients were probable SARS with atypical presentations. Overall mortality was 11.8%.

CONCLUSIONPatients infected with the SARS coronavirus had a wide clinical presentation with non-specific symptoms.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral ; analysis ; Child ; Child, Preschool ; DNA, Viral ; analysis ; Diagnosis, Differential ; Female ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; genetics ; immunology ; Severe Acute Respiratory Syndrome ; diagnosis ; epidemiology ; virology ; Severity of Illness Index ; Singapore ; epidemiology

OBJECTIVETo identify the etiologic agents from children who had been clinically diagnosed as severe acute respiratory syndrome (SARS) during the epidemic in Beijing and to characterize the transmissibility of SARS from those children to others.

METHODSOne hundred and seventy-seven serum specimens were collected during the period of June to August, 2003 from children and adults who had been clinically diagnosed as SARS and who closely contacted with those diagnosed as SARS during SARS epidemic in Beijing. Serum specimens were also collected from 49 children from Anhui province which was non-epidemic region and 93 healthy kindergarten children without history of contacting with SARS patients in Beijing during SARS epidemic. Serum specimens collected from 90 healthy kindergarten children in Beijing in September 2002 were included in the study. All the 409 serum specimens were tested for specific antibodies against SARS-associated coronavirus (SARS-CoV) by different methods including ELISA for specific IgM and IgG, whole antibodies against SARS-CoV, IFA for specific IgM and IgG against SARS-CoV, and Western-blot for IgG to expressed N protein from SARS-CoV.

RESULTSThe positive rates of specific IgG and whole antibodies against SARS-CoV ranged from 39.1% to 43.5% in the children who had been clinically diagnosed as SARS, zero in children and 6.0% to 9.0% in adults who had closely contacted with the clinically diagnosed SARS children. Among those clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 57.1% to 71.4%. In children and adults who closely contacted with these clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 0 to 9.7% and 4.4% to 7.1%, respectively. None of the serum specimens collected from healthy children before and during epidemic in Beijing and children from non-epidemic region was positive when IFA methods and ELISA with Beier kits were used for detection, but some were positive when ELISA with the diagnostic kit from other source was applied.

CONCLUSIONThe positive rates of specific IgG and whole antibodies against SARS-CoV in children who had been clinically diagnosed as SARS were around 40%, which is much lower than the positive rate in clinically diagnosed adult SARS patients, indicating that a large proportion of those "SARS" children were infected with respiratory viruses other than SARS-CoV during SARS epidemic in Beijing. Some of the children who closely contacted with children and adults SARS patients showed positive SARS-CoV antibodies, suggesting that asymptomatic infections may occur. The value of some approved diagnostic kit at least in children for SARS etiological diagnosis needs to be analyzed further.

Adult ; Antibodies, Viral ; blood ; Blotting, Western ; Case-Control Studies ; Child ; China ; epidemiology ; Contact Tracing ; Disease Outbreaks ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; SARS Virus ; immunology ; isolation & purification ; Severe Acute Respiratory Syndrome ; blood ; diagnosis ; epidemiology ; virology

OBJECTIVETo clone and express nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus, and to evaluate its antigenicity and application value in the development of serological diagnostic test for SARS.

METHODSSARS-associated coronavirus N protein gene was amplified from its genomic RNA by reverse transcript nested polymerase chain reaction (RT-nested-PCR) and cloned into pBAD/Thio-TOPO prokaryotic expression vector. The recombinant N fusion protein was expressed and purified, and its antigenicity and specificity was analyzed by Western Blot, to establish the recombinant N protein-based ELISA for detection of IgG antibodies to SARS-associated coronavirus, and SARS-associated coronavirus lysates-based ELISA was compared parallelly.

RESULTSThe recombinant expression vector produced high level of the N fusion protein after induction, and that protein was purified successfully by affinity chromatography and displayed higher antigenicity and specificity as compared with whole virus lysates.

CONCLUSIONThe recombinant SARS-associated coronavirus N protein possessed better antigenicity and specificity and could be employed to establish a new, sensitive, and specific ELISA for SARS diagnosis.

Antibodies, Viral ; blood ; Blotting, Western ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Genome, Viral ; Humans ; Immunoglobulin G ; blood ; Nucleocapsid Proteins ; genetics ; immunology ; metabolism ; RNA, Viral ; genetics ; Recombinant Proteins ; isolation & purification ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; genetics ; immunology ; isolation & purification ; metabolism ; Severe Acute Respiratory Syndrome ; blood ; diagnosis ; virology

OBJECTIVETo compare the sensitivity and specificity of four kits for detection of anti-severe acute respiratory syndrome (SARS)-CoV IgG in sera of SARS patients.

METHODSAnti-SARS-CoV IgG was detected in 99 serial sera from 18 SARS patients and in 123 negative reference sera, using two enzyme linked immunosorbent assays (EIA No. A and No. B) and two indirect immunofluorescence assays (Australian IFA and Euroimmun IFA).

RESULTSAnti-SARS-CoV IgG was not detected in sera collected from SARS patients at the first week after onset by any of the four kits, however, it was detectable in sera obtained at the second week of illness by EIA No. B, and two IFA, but not by EIA No. A, with the positive rates of 57.1% (4/7), 57.1% (4/7) and 42.9% (3/7), respectively. The anti-SARS-CoV IgG was first determined in sera on the 9th day by Euroimmun IFA, 12th day by EIA No. B, 13th day by Australian IFA, and 16th day by EIA No. A. The positive rates of antibody on the 3rd week after onset were 84.2% (16/19), 94.7% (18/19), 78.9% (15/19) and 52.6% (10/19) respectively. They were identical since the 4th week after the disease onset. Through detection of 123 negative reference sera, the specificity of EIA No. A and two IFA was 100%, with exception of 94.9% for EIA No. B.

CONCLUSIONThe sensitivity and specificity of the two IFAs were relatively higher than that of the two EIAs. The quality of the two homemade EIAs should be improved.

Antibodies, Viral ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoglobulin G ; blood ; Male ; Reagent Kits, Diagnostic ; SARS Virus ; immunology ; isolation & purification ; Sensitivity and Specificity ; Severe Acute Respiratory Syndrome ; diagnosis ; immunology ; virology

OBJECTIVETo investigate the significance of detecting specific serum IgG antibodies in clinical diagnosis of SARS as well as affecting factors.

METHODSEnzyme-linked immunoassay kit for SARS coronavirus antibodies developed by HuaDa Biological Company was applied to detect specific serum IgG from SARS patients and the production of SARS specific antibodies among patients of different age groups, sex and with or without steroid treatment were statistically compared.

RESULTSOut of 121 patients studied, 71.1% were SARS specific IgG positive. Patients younger than 15 years, between 15 to 59 years, older than 59 years had positive rates of 60.0%, 70.2%, and 85.7%, respectively with no statistically significance (P=0.766); patients with or without steroid treatment showed positive rates of 70.6% and 72.4%, respectively (P=0.84); patients exhibiting either severe or light syndromes showed positive rates of 78.1% and 67.4%, respectively (P=0.493); both male and female patients showed the same positive rate of 71.1%.

CONCLUSIONThe sensitivity of the SARS specific IgG kit utilized needs to be further improved. The production of SARS IgG is not notably correlated with sex, age, seriousness of symptoms, and steroid treatment.

Adolescent ; Adult ; Aged ; Antibodies, Viral ; blood ; Child ; Female ; Humans ; Immunoglobulin G ; immunology ; Male ; Middle Aged ; SARS Virus ; immunology ; Sensitivity and Specificity ; Severe Acute Respiratory Syndrome ; diagnosis ; immunology

BACKGROUNDTo clarify the difference and significance of T-lymphocyte subsets in differential diagnosis between severe acute respiratory syndrome SARS) and common atypical pneumonia.

METHODSTotally 100 patients hospitalized in Beijing Ditan Hospital since March to June 2003 with clinical diagnosis of SARS were involved in this study. These patients courses of disease were over 3 weeks. These patients were divided into two groups, SARS group and common atypical pneumonia group (non-SARS group). The counts of CD3+, CD4+ and CD8+ T-lymphocyte of two groups were systematically recorded and analyzed.

RESULTSSixty-five of the patients were confirmed to have common type of SARS, including 26 males and 39 females, 50 cases received methylprednisolone treatment. Thirty-five cases had common atypical pneumonia (non-SARS), 21 were males while 14 were females, 20 cases received methylprednisolone treatment. All the cases of two groups were cured in the end. The SARS patients T-lymphocyte counts decreased first and then increased. Before 15 days of disease course, mean CD3+, CD4+, CD8+ T-lymphocyte counts of SARS patients were decreased apparently (694+/-568/microl, 441+/-356/microl, 309+/-462/microl). After 15th day of disease course, the counts gradually returned to normal CD3+, CD4+, CD8+ T-lymphocyte counts of non-SARS patients were normal. Compared with patients of the same group who were not treated with glucocorticoids, T-lymphocyte counts of non-SARS patients treated with glucocorticoids had no obvious difference. But glucocorticoids had some effect on SARS patients recovery of cellular immune function, i.e., it delayed the recovery by about 6 days.

CONCLUSIONWith or without treatment with glucocorticoids,the lowered CD3+, CD4+, CD8+ T-lymphocyte counts in the early stage are of very important significance in differential diagnosis between severe acute respiratory syndrome and common atypical pneumonia.

Adult ; Diagnosis, Differential ; Female ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Pneumonia ; diagnosis ; immunology ; Severe Acute Respiratory Syndrome ; diagnosis ; immunology ; T-Lymphocyte Subsets ; immunology