As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to detoriating clinical conditions such as, cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute phase reactants and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals.In the majority of the patients, a one-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing anti-viral T cell and antibody immunity. The IgM, IgA and IgG type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place.High viral-load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of with contribute to a poor prognosis. Elevated levels of acute phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome and novel approachs to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.
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Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management.
Coronavirus disease 2019 (COVID-19), a newly emerged respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become pandemic. Most patients with COVID-19 exhibit mild to moderate symptoms, but approximately 15% progress to severe pneumonia and about 5% eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure1,2. The mainstay of clinical treatment consists of symptomatic management and oxygen therapy, with mechanical ventilation for patients with respiratory failure. Although several antiviral drugs, including the nucleotide analogue remdesivir, are being actively tested, none has been specifically approved for COVID-19. In addition to vaccine development and approaches that directly target the virus or block viral entry, treatments that address the immunopathology of the infection have become a major focus.
Coronavirus disease 2019 (COVID-19), a newly emerged respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become pandemic. Most patients with COVID-19 exhibit mild to moderate symptoms, but approximately 15% progress to severe pneumonia and about 5% eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure1,2. The mainstay of clinical treatment consists of symptomatic management and oxygen therapy, with mechanical ventilation for patients with respiratory failure. Although several antiviral drugs, including the nucleotide analogue remdesivir, are being actively tested, none has been specifically approved for COVID-19. In addition to vaccine development and approaches that directly target the virus or block viral entry, treatments that address the immunopathology of the infection have become a major focus.
Another approach to alleviate COVID-19-related immunopathology involves mesenchymal stem cells (MSCs), which exert anti-inflammatory and anti-apoptotic effects, can repair pulmonary epithelial cell damage and promote alveolar fluid clearance. Encouraged by preclinical and clinical studies that confirmed their safety and efficacy in non-COVID-19-related pathologies, clinical trials of MSC-based therapy in patients with severe COVID-19 have been initiated in China and two trials are currently ongoing.
To further help our fight against COVID-19, prognostic biomarkers need to be identified for patients at high risk of developing ARDS or multiple organ failure. Age (above 50 years) has emerged as one independent risk factor for severe disease, raising concerns about the feasibility of generating a potent vaccine to induce efficient cellular and humoral responses in this population. In addition, it appears that patients with COVID-19 and hypertension or diabetes are more likely to develop severe disease. Delineating the mechanisms behind these chronic diseases for worsening disease outcome, as well as a better understanding of SARS-COV-2 immune-escape mechanisms, may provide clues for the clinical management of the severe cases.
It is of utmost importance that successful standardized treatment protocols for severe cases are recommended globally to fight the COVID-19 pandemic. The combined use of anti-inflammatory and antiviral drugs may be more effective than using either modality alone. Based on in vitro evidence for inhibiting SARS-CoV-2 replication and blocking SARS-CoV-2 infection-induced pro-inflammatory cytokine production10, a Chinese traditional medicine has demonstrated clinical efficacy (Nanshan Zhong, personal communication).
Another, so-far under-investigated pathogenic factor that may affect therapeutic outcome involves stress-induced disorders of the neuroendocrine–immune crosstalk. It is well known that cytokines released in the context of innate immune responses to viral infections can induce the neuroendocrine system to release glucocorticoids and other peptides, which can impair immune responses. Infectious SARS-CoV-2 viral particles have been isolated from respiratory, faecal and urine samples. Whether SARS-CoV-2 can infect the central nervous system, facilitating the release of inflammation-induced pathological neuroendocrine mediators that impact on respiratory function and ARDS pathogenesis, warrants investigation
To further help our fight against COVID-19, prognostic biomarkers need to be identified for patients at high risk of developing ARDS or multiple organ failure. Age (above 50 years) has emerged as one independent risk factor for severe disease, raising concerns about the feasibility of generating a potent vaccine to induce efficient cellular and humoral responses in this population. In addition, it appears that patients with COVID-19 and hypertension or diabetes are more likely to develop severe disease. Delineating the mechanisms behind these chronic diseases for worsening disease outcome, as well as a better understanding of SARS-COV-2 immune-escape mechanisms, may provide clues for the clinical management of the severe cases.
It is of utmost importance that successful standardized treatment protocols for severe cases are recommended globally to fight the COVID-19 pandemic. The combined use of anti-inflammatory and antiviral drugs may be more effective than using either modality alone. Based on in vitro evidence for inhibiting SARS-CoV-2 replication and blocking SARS-CoV-2 infection-induced pro-inflammatory cytokine production10, a Chinese traditional medicine has demonstrated clinical efficacy (Nanshan Zhong, personal communication).
Another, so-far under-investigated pathogenic factor that may affect therapeutic outcome involves stress-induced disorders of the neuroendocrine–immune crosstalk. It is well known that cytokines released in the context of innate immune responses to viral infections can induce the neuroendocrine system to release glucocorticoids and other peptides, which can impair immune responses. Infectious SARS-CoV-2 viral particles have been isolated from respiratory, faecal and urine samples. Whether SARS-CoV-2 can infect the central nervous system, facilitating the release of inflammation-induced pathological neuroendocrine mediators that impact on respiratory function and ARDS pathogenesis, warrants investigation
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