Immunological findings in a group of individuals who were non-responders to standard two-dose SARS-CoV-2 vaccines (preprint)

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic. The virus has infected more than 505 million people and caused more than 6 million deaths. However, data on non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of the study is to comprehensively compare the immunological characteristics of non-responders to SARS-CoV-2 vaccines in the 18-59 years with that in the 60 years and older using internationally recognized cutoff values. Participants included 627 individuals who received physical examinations and volunteered to participate in COVID-19 vaccination from the general population. The main outcome was an effective seroconversion characterized by anti-SARS-CoV-2 spike IgG level of at least 4-fold increase from baseline. Profiling of naive immune cells was analyzed prior to vaccination to demonstrate baseline immunity. Outcomes of effective seroconversion in the 18-59 years with that in the 60 years and older were compared. The quantitative level of the anti-spike IgG was significantly lower in the 60 years and older and in men among the 18-59 years. There were 7.5% of non-responders among the 18-59 years and 11.7% of non-responders in the 60 years and older using the 4-fold increase parameter. The effective seroconversion rate was significantly related to the level of certain immune cells before vaccination, such as CD4 cells, CD8 cells and B cells and the age. An individual with a titer of anti-SARS-CoV-2 spike IgG that is below 50 BAU/mL might be considered a non-responder between 14-90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended for non-responders as soon as possible to reduce disease severity and mortality.

Interpretation of non-responders to SARS-CoV-2 vaccines using WHO International Standard (preprint)

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with more than 485 millions infected. Questions about non-responders to SARS-CoV-2 vaccines remain unaddressed. Here, we report data from people after administering the complete dose of SARS-CoV-2 vaccines using the World Health Organization International Standard for anti-SARS-CoV-2 immunoglobulin. Our study showed that immune cells such as CD4 cells, CD8 cells, and B cells and anti-spike immunoglobulin G levels were significantly reduced in the elderly. There were 7.5% non-responders among the 18–59 yr group and 11.7% in the ≥60 yr group. A titer of anti-SARS-CoV-2 spike immunoglobulin G is blew 50 BAU/mL to be considered as non-responders at intervals of 30 to 90 days after the last vaccine dose. Booster vaccination may be recommended for non-responders to reduce the disease severity and mortality.

Improving Google Flu Trends for COVID-19 Estimates Using Weibo Posts

While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (p < 0.01) to 0.86 (p < 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.

Clinical research COVID-19 disease: novel clinical manifestations and therapeutic exploration

Introduction: This study aims to provide further clarifications on some new clinical characteristics of COVID-19 recently discovered by our research group. Material and methods: In this single-centred, retrospective study, we collected all confirmed cases of COVID-19 diagnosed in Dazhou, Sichuan, China from January 23 to February 25, 2020. All the cases were either imported from Wuhan or transmitted in family clusters. We analysed general information on all patients. Meanwhile, the contents of lactic acid, Fib-C, and D-dimer in the serum of patients were detected.

SARS-CoV-2-specific T cell immunity in mild hypertensive patients with COVID-19 in China (preprint)

Background: Coronavirus disease 2019 (COVID-19) pandemic leads to severe illness, life-threatening complications, and death, especially in high-risk groups such as elderly people and individuals with hypertension or diabetes. It has been shown that SARS-CoV-2-specific T cell immunity is important for the patient recovery from COVID-19. However, there are no reports about SARS-CoV-2-specific T cell immunity in hypertensive patients with COVID-19.Results: In this work, through the study of a cohort of 76 mild cases of hypertensive patients with COVID-19 and 572 hypertensive patients without COVID-19, we discovered that SARS-CoV-2 infection in hypertensive patients is characterized by T lymphopenia during the acute phase and the high frequency of CD4+CD25+, CD4+CD45RO+, and CD8+CD28+ T cells in the recovery phase. We also showed that strong SARS-CoV-2-specific CD4+IFNg+ T cell responses are associated with high SARS-CoV-2-specific antibody titers in hypertensive patients with COVID-19.Conclusions: The subsets of T cells including CD4+CD25+, CD4+CD45RO+, and CD8+CD28+ could be valuable biomarkers for the estimation of the progression of hypertensive patients with COVID-19. The hypertensive patients with COVID-19 exhibits T lymphopenia during the acute phase and have proper immune function during the recovery phase. This study may provide valuable insights for the monitoring and treatment of hypertensive patients with COVID-19.

Loss expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19 (preprint)

The dynamic immunological characteristics of COVID-19 patients are essential for clinicians to understand the disease progression. Our data showed that the immune system and function have gradually remodeled and declined with age from 16-91 years old in 25,239 healthy controls. Analyzing the relationship between the number of lymphocytes and age showed that lymphocytes and subsets tended to decline with age significantly, whereas, the number of natural killer cells tended to increase with age significantly. SARS-CoV-2 specific immunity has declined with age in fatal cases. Furthermore, SARS-CoV-2 specific immunity is associated with survival time in fatal cases. The loss expansion of SARS-CoV-2 specific immunity could be expanded in vitro. A concurrent decline in SARS-CoV-2 specific cellular and humoral immunity and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings have provided a basis for further analysis of SARS-CoV-2 specific immunity and understanding the pathogenesis of fatal COVID-19 patients.

Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population (preprint)

Background In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population. Methods Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020. Results The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n = 44), severe or critical patients (n = 25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; P < 0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Conclusions In this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.

Mortality of COVID-19 is Associated with Cellular Immune Function Compared to Immune Function in Chinese Han Population (preprint)

In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in Chinese Han population is limited. Our objective is to describe the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in the Chinese Han population. In this case series of 752 patients, the full spectrum of cases is described. Fever was present in 86-90% of the patients. The second most common symptom was cough (49.1-51.0%), fatigue (25.2-27.1%), sputum (20.0-23.1%), and headache (9.8-11.1%). the mortality rate is 4.6% in Wuhan, 1.9% in Beijing, and 0.9% in Shanghai. Our findings showed that the levels of lymphocytes were 0.8(IQR, 0.6-1.1)109/L in Wuhan, 1.0(IQR, 0.7-1.4)109/L in Beijing, and 1.1 (IQR, 0.8-1.5) 109/L in Shanghai before admission to hospitals, respectively, indicating that cellular immune function might relate to the mortality. Based on the reference ranges of normal Chinese Han population and the data of the critically ill patients we have observed, it is recommended that reference ranges of people at high risk of COVID-19 infection are CD3+ lymphocytes below 900 cells/mm3, CD4+ lymphocytes below 500 cells/mm3, and CD8+ lymphocytes below 300 cells/mm3.