A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-e ects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n=1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 109/L, 95% CI 0.83–1.03 109/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay.
The current reports of COVID-19 focus on the respiratory system, however, intestinal infections caused by SARS-CoV-2 are also worthy of attention. This paper reported persistence of intestinal SARS-CoV-2 infection leads to re-admission after pneumonia resolved in three cases with COVID-19.
Cytotoxic CD8(+) T lymphocytes (CTLs) play an important role in antiviral immunity. Several human HLA-A*0201 restricted CTL epitopes of severe acute respiratory syndrome (SARS) spike (S) protein have been identified in HLA-A*0201 transgenic (Tg) mice, but the mechanisms and properties of immune responses are still not well understood. In this study, HLA-A*0201 Tg mice were primed intramuscularly with SARS S DNA and boosted subcutaneously with HLA-A*0201 restricted peptides. The lymphocytes from draining lymph nodes, spleens and lungs were stimulated with the cognate peptides. Three different methods (ELISA, ELISPOT and FACS) were used to evaluate the immune responses during short and long periods of time after immunization. Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface. IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes. The phenotype of the CD8(+) T cells was characterized based on the expression of IFN-γ. Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low). Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection. We provide novel information in cellular immune responses of SARS S antigen-specific CD8(+) T cells, which are important in the development of vaccine against SARS-CoV infection.
The induction of antigen specific memory CD8(+) T cells in vivo is very important to new vaccines against infectious diseases. In the present study, we aimed to evaluate the immune responses of peptide-specific CD8(+) T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants. Furthermore, the generation, distribution and phenotype of long-lasting peptide-specific memory CD8(+) T cells were assessed by ELISA, ELISPOT and flow cytometry. Our results showed that antigen specific CD8(+) T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes. Furthermore, the frequency of peptide-specific CD8(+) T cells was dramatically increased after both prime and boost immunization with peptides plus CpG ODN, whereas slight enhancements were induced following boost vaccination with peptides plus PolyI:C or R848. SARS-CoV S peptide-specific IFN-γ(+)CD8(+) T cells were distributed throughout the lymphoid and non-lymphoid tissues. Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8(+) T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB(+) and CD62L(-) and possessed long-term survival ability in vivo. Taken together, our results implied that HLA-A*0201 restricted SARS-CoV S epitopes plus CpG ODN might be the superior candidates for SARS vaccine.
Abstract The world is experiencing one of the most difficult moments in history with COVID‐19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found. Antibody drugs have never been absent in epidemics such as SARS, MERS, HIV, Ebola, and so on in the past two decades. At present, while research on the SARS‐CoV‐2 vaccine is in full swing, antibody drugs are also receiving widespread attention. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Here, we summarize the therapeutic antibodies against SARS‐CoV‐2, as well as the research using ACE2 recombinant protein or ACE2‐Ig fusion protein. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Due to the rapid progress in the field of therapeutic antibodies for COVID‐19 treatment, we summarized the neutralizing antibody drugs and fusion protein drugs that have attracted high attention at present, discussed the existing problems in the current application of antibodies drugs for COVID‐19, and prospected the future research direction in this field.
AbstractThe RNA-dependent RNA polymerase (RdRp) of SARS coronavirus (SARS-CoV) is essential for viral replication and a potential target for anti-SARS drugs. We report here the cloning, expression, and purification of the N-terminal GST-fused SARS-CoV RdRp and its polymerase catalytic domain in Escherichia coli. During purification, the full-length GST-RdRp was found to cleave into three main fragments: an N-terminal p12 fragment, a middle p30 fragment, and a C-terminal p64 fragment comprising the catalytic domain, presumably due to bacterial proteases. Biochemical assays show that the full-length GST-RdRp has RdRp activity and the p64 and p12 fragments form a complex that exhibits comparable RdRp activity, whereas the GST-p64 protein has no activity, suggesting that the p12 domain is required for polymerase activity possibly via involvement in template-primer binding. Nonnucleoside HIV-1 RT inhibitors are shown to have no evident inhibitory effect on SARS-CoV RdRp activity. This work provides a basis for biochemical and structural studies of SARS-CoV RdRp and for development of anti-SARS drugs.
Abstract. Background:. With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time. Methods:. We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7). Results:. Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively. Conclusions:. Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.
Publisher: Springer Science and Business Media LLC
SARS coronavirus is an RNA virus whose replication is error-prone, which provides possibility for escape of host defenses, and even leads to evolution of new viral strains during the passage or the transmission. Lots of variations have been detected among different SARS-CoV strains. And a study on these variations is helpful for development of efficient vaccine. Moreover, the test of nucleic acid characterization and genetic stability of SARS-CoV is important in the research of inactivated vaccine. The whole genome sequences of two SARS coronavirus strains after passage in Vero cell culture were determined and were compared with those of early passages, respectively. Results showed that both SARS coronavirus strains have high genetic stability, although nearly 10 generations were passed. Four nucleotide variations were observed between the second passage and the 11th passage of Sino1 strain for identification of SARS inactivated vaccine. Moreover, only one nucleotide was different between the third passage and the 10th passage of Sino3 strain for SARS inactivated vaccine. Therefore, this study suggested it was possible to develop inactivated vaccine against SARS-CoV in the future.