BACKGROUND: The coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown. METHODS: The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS: A total of 65 SARS-CoV-2–positive patients were classified as having mild ( n = 30), severe ( n = 20), and extremely severe ( n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4 ⁺ T cells, CD8 ⁺ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4 ⁺ and CD8 ⁺ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ–producing CD8 ⁺ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ–producing CD4 ⁺ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSION: The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4 ⁺ and CD8 ⁺ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection. FUNDING: This work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).

Liposomes carrying MBD2 siRNA protect mice against BLM-induced lung injury and fibrosis by targeting macrophage M2 program.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with a poor prognosis. Although many factors have been identified that possibly trigger or aggravate IPF, such as viral infection, the exact cause of IPF remains unclear. Until now, there has been no systematic review to assess the role of viral infection in IPF quantitatively. This meta-analysis aims to present a collective view on the relationship between viral infection and IPF. We searched studies reporting the effect of viral infection on IPF in the PubMed, Embase, Cochrane Library, Web of Science, and Wiley Online Library databases. We calculated ORs with 95% CIs to assess the risk of virus in IPF. We also estimated statistical heterogeneity by using I² and Cochran Q tests and publication bias by using the funnel plot, Begg test, Egger test, and trim-and-fill methods. Regression, sensitivity, and subgroup analyses were performed to assess the effects of confounding factors, such as sex and age. We analyzed 20 case-control studies from 10 countries with 1,287 participants. The pooled OR of all viruses indicated that viral infection could increase the risk of IPF significantly (OR, 3.48; 95% CI, 1.61-7.52; P = .001), but not that of exacerbation of IPF (OR, 0.99; 95% CI, 0.47-2.12; P = .988). All analyzed viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8), were associated with a significant elevation in the risk of IPF, except human herpesvirus 6 (HHV-6). The presence of persistent or chronic, but not acute, viral infections, including EBV, CMV, HHV-7, and HHV-8, significantly increases the risk of developing IPF, but not exacerbation of IPF. These findings imply that viral infection could be a potential risk factor for IPF.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

In December 2019, an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) infection occurred in Wuhan, and rapidly spread to worldwide, which has attracted many people's concerns about the patients. However, studies on the infection status of medical personnel is still lacking. A total of 54 cases of SARS‐Cov‐2 infected medical staff from Tongji Hospital between 7 January and 11 February 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. From 7 January to 11 February 2020, 54 medical staff of Tongji Hospital were hospitalized due to coronavirus disease 2019 (COVID‐19). Most of them were from other clinical departments (72.2%) rather than emergency department (3.7%) or medical technology departments (18.5%). Among the 54 patients with COVID‐19, the distribution of age had a significant difference between non‐severe type and severe/critical cases (median age: 47 years vs 38 years; P = .0015). However, there was no statistical difference in terms of gender distribution and the first symptoms between theses two groups. Furthermore, we observed that the lesion regions in SARS‐Cov‐2 infected lungs with severe‐/critical‐type of medical staff were more likely to exhibit lesions in the right upper lobe (31.7% vs 0%; P = .028) and right lung (61% vs 18.2%; P = .012). Based on our findings with medical staff infection data, we suggest training for all hospital staff to prevent infection and preparation of sufficient protection and disinfection materials.

Following acute infection, individuals with coronavirus disease 2019 (COVID-19) may still shed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative and positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people (65 years old, median age) with a history of mild infection. Infectious SARS-CoV-2 RNA was isolated from the respiratory tract (sputum), where high viral RNA and protein levels were found. Real-time polymerase chain reaction experiments showed that the viral load in long-term carriers was significantly lower (median cycle threshold [Ct] = 32) than in patients with acute infection (median Ct = 27). All nine full-length genomes of samples obtained in March–April 2020 matched early viral clades circulating in January–February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.