ABSTRACT
Background: The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, it remains unclear whether immune responses following natural infection can be sustained or potentially prove critical for long-term immune protection against SARS-CoV-2 reinfection. Here, we systematically mapped the phenotypic landscape of SARS-CoV-2-specific immune responses in peripheral blood samples of 4 healthy donors and 13 convalescent patients with COVID-19, including moderate and severe cases, by single-cell RNA sequencing. Results: : The relative percentage of the CD8+ effector memory subset was increased in both convalescent moderate and severe cases, but NKT-CD160 and maginal zone B clusters were decreased. Innate immune responses were attenuated reflected by decreased expression of genes involved in interferon-gamma, leukocyte migration and neutrophil mediated immune response in convalescent COVID-19 patients. Functions of T cell were strengthened in convalescent COVID-19 patients by clear endorsement of increased expression of genes involved in biological processes of regulation of T cell activation, differentiation and cell-cell adhesion. In addition, T cell mediated immune responses were enhanced with remarkable clonal expansions of TCR and increased transition of CD4+ effector memory and CD8+ effector-GNLY in severe subjects. B cell immune responses displayed sophisticated and dual functions during convalescence of COVID-19, providing a novel mechanism that B cell activation was observed especially in moderate while humoral immune response was weakened. Interestingly, HLA class I genes displayed downregulation while HLA class II genes upregulation in both T and B cell subsets in convalescent individuals. Notably, some unique IGV genes in severe patients may facilitate the design of vaccines. Conclusions: : Our collective dataset showed that innate immunity was declined but SARS-CoV-2-specific T cell responses were retained even strengthened whereas sophisticated and dual functions of B cells, including declined humoral immunity were presented at several months following infections, which provided insights into evaluation of possibility of reinfection of exposed individuals with COVID-19 and facilitation to design of effective therapeutics and vaccines.
Subject(s)
COVID-19ABSTRACT
Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, oncologists face new challenges and they need to adjust their cancer management strategies as soon as possible to reduce the risk of SARS-CoV-2 infection and tumor recurrence. However, data on cancer patients with SARS-CoV-2 infection remains scarce. Methods: We performed a retrospective study of 223 cancer patients with SARS-CoV-2 from 26 hospitals in Hubei, China. An individualized nomogram was constructed based on multivariable Cox analysis. Considering the convenience of the nomogram application, an online tool was also created by shiny app. C-index, calibration curves and decision curve analysis (DCA) were performed to verify the prediction performance and clinical application of the nomogram.Results: Among cancer patients with SARS-CoV-2, there were significant differences in clinical characteristics between survivors and non-survivors, and lung cancer patients had similar short-time survival with other cancer patients. Male, dyspnea, elevated PCT, increased heart rate, elevated D-dimers, decreased platelets and so on were risk factors for these patients. Furthermore, good prediction performance of the online tool (dynamic nomogram: https://covid-19-prediction-tool.shinyapps.io/DynNomapp/). was also fully demonstrated with the C-index of 0.841 (95% CI: 0.782 - 0.900) in the development cohort and 0.780 (95% CI: 0.678-0.882) in the validation cohort. Conclusion: Overall, cancer patients with SARS-CoV-2 had unique clinical features, and the established online tool could guide clinicians to predict the prognosis of patients and to develop more rational treatment strategies for cancer patients during the COVID-19 epidemic.
Subject(s)
COVID-19ABSTRACT
Background: Cancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and Participants: Data of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. Results: A total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. Conclusions: This is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.
Subject(s)
Critical Illness , Neoplasms , Virus Diseases , Death , COVID-19ABSTRACT
Background Since December 2019, a novel corona virus disease named COVID-19 outbreak in Wuhan, China and spread worldwide then. Active prevention and control measures have been carried out in China, such as vigorous publicity, active screening and rapid isolation. As the major epidemic area, the passages in and out of Wuhan were temporarily closed since January 23. We aimed to demonstrate the effectiveness of rigorous measures by comparing the characteristics of patients hospitalized before and after implementation of vital measures. Methods Clinical data of patients admitted to hospital with COVID-19 during January 17-23 (Phase I) and February 3-9 (Phase II) were collected and compared. The cut-off date for follow-up was March 13, 2020. Results Of 176 patients with COVID-19, 97 were admitted in Phase I (43 [44.3%] male; mean age: 47.7), and 79 were in Phase II (33 [41.8%] male; mean age: 50.1). The proportions of severe cases were 21.6% and 10.1% respectively. Fewer patients had comorbidities (13 [16.5%] vs. 7 [7.2%]) and more asymptomatic patients were in Phase II (27.8% vs. 13.9%). Patients in Phase II had less fever (53.2% vs. 70.1%), cough (34.2% vs. 52.6%) and myalgia (11.4% vs.28.9%), while more diarrhea (11.4% vs. 2.1%). Lymphopenia and elevated CRP, as well as eosinopenia and elevated SAA were common in two groups, but all of that were significantly better in Phase II. More patients in Phase II preformed normal CT image on admission (10 [12.7%] vs. 7 [7.2%]). And lower CT scores (3 [2-4] vs. 2 [1-3]) were observed in Phase II. Up to cut-off date, average response time on CT image were 11.2 and 8.1 days in Phase I and II respectively. Shorter average hospitalized days were in Phase II (18.9 vs. 23.3 days). Four patients (4.1%) in Phase I and two (2.5%) in Phase II died. Conclusions Various actions (including vigorous publicity, active screening and rapid isolation) prompted more early patients with COVID-19 found, diagnosed and remedied, leading to good prognosis. Call for pretty attention to the epidemics of COVID-19 and timely measures around the world.
Subject(s)
Diarrhea , Fever , Myalgia , COVID-19 , LymphopeniaABSTRACT
Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.
Subject(s)
Coronavirus Infections , Emergencies , COVID-19ABSTRACT
Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.