An epidemic of acute respiratory syndrome in humans, which appeared in Wuhan, China in December 2019, was caused by a novel coronavirus (SARS-CoV-2). This disease was named as "Coronavirus Disease 2019" (COVID-19). SARS-CoV-2 was first identified as an etiological pathogen of COVID-19, belonging to the species of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV). The speed of both the geographical transmission and the sudden increase in numbers of cases is much faster than SARS and Middle East respiratory syndrome (MERS). COVID-19 is the first global pandemic caused by a coronavirus, which outbreaks in 211 countries/territories/areas. The vaccine against COVID-19, regarded as an effective prophylactic strategy for control and prevention, is being developed in about 90 institutions worldwide. The experiences and lessons encountered in the previous SARS and MERS vaccine research can be used for reference in the development of COVID-19 vaccine. The present paper hopes to provide some insights for COVID-19 vaccines researchers.
Betacoronavirus ; immunology ; Biomedical Research ; Coronavirus Infections ; epidemiology ; immunology ; prevention & control ; virology ; Humans ; Internationality ; Middle East Respiratory Syndrome Coronavirus ; immunology ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; immunology ; prevention & control ; virology ; SARS Virus ; immunology ; Severe Acute Respiratory Syndrome ; immunology ; Viral Vaccines ; immunology

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

OBJECTIVES: To explore the significance of coagulation and immune function indicators in clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19). METHODS: All patients with COVID-19 diagnosed and treated in First People's Hospital of Yueyang from January to March 2020 were enrolled. The general data of patients were collected. The patients were assigned into a light group (=20), an ordinary group (=33), a severe group (=23), and a critically severe group (=7) according to the severity of the disease. Coagulation and immune function indicators of each group were compared, and the relevance of coagulation and immune function indicators was analyzed. RESULTS: The age of COVID-19 patients in Yueyang City was mainly between 45 and 65 years old. There was a significant difference in the coagulation function and immune-related indicators in each group of patients (all <0.05). CONCLUSIONS There are some abnormalities in coagulation and immune function in patients with COVID-19, which possess significance for clinical diagnosis and treatment of the disease.
Aged ; Betacoronavirus ; Blood Coagulation ; China ; Coronavirus Infections ; diagnosis ; immunology ; Humans ; Immune System ; physiopathology ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; immunology

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

The COVID-19 pandemic is still raging across the world. Everyday thousands of infected people lost their lives. What is worse, there is no specific medicine and we do not know when the end of the pandemic will come. The nearest global pandemic is the 1918 influenza, which caused about 50 million deaths and partly terminate the World War Ⅰ. We believe that no matter the virus H1N1 for the 1918 influenza or 2019-nCoV for COVID-19, they are essentially the same and the final cause of death is sepsis. The definition and diagnostic/management criteria of sepsis have been modified several times but the mortality rate has not been improved until date. Over decades, researchers focus either on the immunosuppression or on the excessive inflammatory response following trauma or body exposure to harmful stimuli. But the immune response is very complex with various regulating factors involved in, such as neurotransmitter, endocrine hormone, etc. Sepsis is not a kind of disease, instead a misbalance of the body following infection, trauma or other harmful stimulation. Therefore we should re-think sepsis comprehensively with the concept of systemic biology, i.e. inflammationomics.
Betacoronavirus ; Coronavirus Infections ; complications ; epidemiology ; immunology ; Humans ; Immune Tolerance ; Inflammation ; complications ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; complications ; epidemiology ; immunology ; Pandemics ; Pneumonia, Viral ; complications ; epidemiology ; immunology ; Sepsis ; etiology

Antibodies, Viral ; blood ; Betacoronavirus ; immunology ; Coronavirus Infections ; diagnosis ; Gold Colloid ; chemistry ; Humans ; Immunoassay ; methods ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Pandemics ; Pneumonia, Viral ; diagnosis ; Reagent Kits, Diagnostic

OBJECTIVE: To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19). METHODS: Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed. RESULTS: The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab. CONCLUSIONS For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.
Antibodies, Monoclonal, Humanized ; administration & dosage ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; blood ; immunology ; therapy ; Cytokine Release Syndrome ; therapy ; Humans ; Pandemics ; Plasma Exchange ; standards ; Pneumonia, Viral ; blood ; immunology ; therapy ; Prothrombin Time ; Treatment Outcome

OBJECTIVE: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. METHODS: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3T, CD4 T, CD8 T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. RESULTS: On D1 of admission, the numbers of peripheral blood CD3 T, CD4 T, CD8 T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3 T, CD8 T and CD4 T cells gradually recovered and showed a linear growth trend (linear fitting equation: =18.59+109.4, <0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. CONCLUSIONS In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.
Betacoronavirus ; isolation & purification ; Cell Count ; Coronavirus Infections ; diagnosis ; drug therapy ; immunology ; physiopathology ; Critical Illness ; Cytokines ; blood ; Female ; Humans ; Methylprednisolone ; administration & dosage ; adverse effects ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; immunology ; physiopathology ; T-Lymphocyte Subsets ; drug effects ; Treatment Outcome

The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins. Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response. Human highly pathogenic coronaviruses are hosted by humans and vertebrates. Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes. This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses.
Animals ; Betacoronavirus ; physiology ; Coronavirus Infections ; immunology ; transmission ; virology ; Humans ; Middle East Respiratory Syndrome Coronavirus ; physiology ; Pandemics ; Pneumonia, Viral ; immunology ; transmission ; virology ; SARS Virus ; physiology ; Virus Replication ; physiology

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult