Search

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4+ and CD8+ T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8+ T cells. However, these mice established fewer CD8+ tissue-resident memory T (TRM) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8+ T cells and slows viral RNA clearance but promotes CD8+ TRM cell establishment.

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), the pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding has not been well characterized., Methods: In our study, 652 patients in Wuhan Designated Hospital were recruited, and their clinical and laboratory findings were extracted and analyzed., Results: The median duration of SARS-CoV-2 RNA detection was 23 days [interquartile range (IQR), 18 days] from symptom onset. Compared to patients with early viral RNA clearance (<23 days after illness onset), we found that patients with late viral RNA clearance (≥23 days) had a higher proportion of clinical features, as follows: symptoms, including fever, dry cough, and sputum production; comorbidities, including hypertension, chronic kidney disease, uremia, chronic liver disease, anemia, hyperlipidemia, and bilateral lung involvement; complications, such as liver injury; delayed admission to hospital; laboratory parameters at baseline, including higher eosinophils, uric acid, cholesterol, triglycerides, and lower hemoglobin; and less treatment with arbidol, chloroquine, or any antivirals. After generalized linear regression, prolonged SARS-CoV-2 RNA shedding was independently associated with younger age; delayed admission to hospital; symptoms including fever, shivering, and sputum production; comorbidities including hypertension, diabetes, cardiovascular disease, anemia, hyperlipidemia, uremia, and lung involvement; and higher alanine aminotransferase (ALT), uric acid, and cholesterol levels at baseline., Conclusions: In conclusion, the factors mentioned above are associated with the negative conversion of SARS-CoV-2 RNA. A deeper insight into virological dynamics will be helpful for establishing patient discharge and quarantine release criteria., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-445). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Severe COVID-19 is associated with a hyperinflammatory state, and corticosteroid therapy may be effective. We review the recent literature and discuss the appropriate dose and duration of corticosteroid therapy. Low-dose corticosteroid therapy is often used to treat COVID-19. However, several doses of methylprednisolone (or prednisolone) have been attempted, ranging from about 40 mg/day to 2 mg/kg/day. Doses may need to be adjusted depending on severity. Corticosteroid therapy is generally administered for a short period over several days. However, COVID-19-induced respiratory failure is often prolonged, so longer administration may be considered. Careful monitoring for complications due to corticosteroid therapy is vital., (2020, National Center for Global Health and Medicine.)

Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4+ and CD8+ T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8+ T cells. However, these mice established fewer CD8+ tissue-resident memory T (TRM) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8+ T cells and slows viral RNA clearance but promotes CD8+ TRM cell establishment. [ABSTRACT FROM AUTHOR]