Characterization of severe and critical COVID-19 infected individuals outside of Wuhan, China (preprint)

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible among people，and the critical cases are still tough to treat, even leading to death. METHODS We retrospectively collected the clinical data of all the critical patients admitted to the Three Gorges Hospital(Chongqing, China) from Jan 20, 2020 to Feb 16, 2020 , whom were divided into improved group and worsen group. At last, we analyzed and compared the differences in laboratory indexes and length of hospital stay of the two groups. RESULT 46 cases were enrolled in the study. Comorbid conditions were present in 25 cases (54.3%). Most cases had symptoms, such as fever, cough, sputum, shortness of breath and dyspnea. The worsen group had a higher APACHE II score of 14(range from 5 to 23) than improved group(5, range from 3 to 7)(p<0.05). 32(69.6%) cases had low level lymphocyte counts (<1.0×109/L), including 8(66.7%) worsen group patients and 24(70.6%) improved group patients. The worsen group was 14.3(range from 8.21 to 18) with the ratio of neutrophil counts to lymphocyte counts, higher than that in improved group((7.33, range from 4.71 to 14.35)(p<0.05). There were faster respiratory frequencies in worsen group(23, range from 20 to 24.75) (p<0.05). And the worsen group had a lower OI(156.5, range from 74.25 to 233) than the other group(206, range from 177.5 to 242.75)(p<0.05). CONCLUSIONS Initial lower lymphocytes and higher APACHE II scores might be relative to the poor prognosis. And most of severe or critical patients had underlying diseases.

Characteristics of Lymphocyte Subsets and Cytokine Profiles of Patients With COVID-19 (preprint)

Background: Abnormalities of lymphocyte subsets and cytokine profiles have been observed in most patients with coronavirus disease (COVID-19). Here, we explore the role of lymphocyte subsets and cytokines at hospital admission in predicting the severity of COVID-19. Methods: : This study included 214 patients with COVID-19 who were treated at Three Gorges Hospital Affiliated with Chongqing University from January 19, 2020 to April 30, 2020. Patients were divided into the non-intensive care unit (ICU) (mild/moderate) group and the ICU (severe/critical) group, according to the severity of the disease. Clinical and laboratory data, including peripheral lymphocyte subsets and cytokines, were analyzed and compared. Logistic regression was used to analyze the predictive factors for ICU admission. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of selected indicators for the severity of COVID-19. Results: : Of the 214 patients enrolled, 161 were non-ICU patients and 53 were ICU patients. At hospital admission, lymphopenia was observed in nearly all of the ICU patients (96.2%) and 84.5% of the non-ICU patients. The absolute number of lymphocytes, CD3 + T cells, CD4 + T cells, CD8 + T cells, CD19 + B cells, and natural killer (NK) cells was lower in the ICU group (659.00 × 10 6 /L, 417.00 × 10 6 /L, 261.00 × 10 6 /L, 140.00 × 10 6 /L, 109.00 × 10 6 /L, 102.00 × 10 6 /L, respectively) than in the non-ICU group (1063.00 × 10 9 /L, 717.00 × 10 6 /L, 432.00 × 10 6 /L, 271.00 × 10 6 /L, 133.00 × 10 6 /L, 143.00 × 10 6 /L, respectively). Interleukin (IL)-6 was significantly higher in the ICU patients than in the non-ICU patients (18.08 pg/mL vs. 3.13 pg/mL). Multivariate logistic regression analysis showed that age (odds ratio: 1.067 [1.034–1.101]), diabetes mellitus (odds ratio: 9.154 [2.710–30.926]), CD3 + T cells (odds ratio: 0.996 [0.994–0.997]), and IL-6 (odds ratio: 1.006 [1.000–1.013]) were independent predictors for the development of severe disease. ROC curve analysis showed that the area under the ROC curve (AUC) of CD3 + T cells and IL-6 was 0.806 (0.737–0.874) and 0.785 (0.705–0.864), respectively, and the cutoff values were 510.5 × 10 6 /L (sensitivity, 71.7%; specificity, 79.5%) and 6.58 pg/mL (77.4%, 74.5%), respectively. There were no statistical differences among all tested indicators of lymphocyte subsets and cytokines between the severe group ( n = 38) and the critical group ( n = 15) at hospital admission or ICU admission. Conclusions: : The levels of lymphocyte subsets decreased and the level of IL-6 increased significantly in the ICU patients compared with the non-ICU patients. Therefore, the number of CD3 + T cells and the level of IL-6 at hospital admission may serve as powerful factors for identifying patients who will have severe disease.

Index and First-Generation Cases in a COVID-19 Outbreak — Jilin Province, China, 2021

What is already known on this topic? Contact tracing and testing with isolated medical care of identified cases is a key strategy for interrupting chains of transmission of COVID-19 and reducing mortality associated with COVID-19. At the early phases of the COVID-19 pandemic, due to test capacity limitations, case finding often started from suspected cases. What is added by this report? The index patient infected 74 individuals who were close contacts that were identified through contact tracing, and exposed individuals were monitored in quarantine with daily polymerase chain reaction (PCR) testing. All individuals were asymptomatic initially, but all PCR-positive individuals eventually developed symptoms. Infectivity was documented up to 8 days before being confirmed as a symptomatic case, approximately 4 days before turning PCR positive. What are the implications for public health practice? During an outbreak, we suggest tracing close contacts from both PCR-positive individuals and suspected cases, rather than from suspected cases alone. Due to the long period of infectivity before turning PCR positive or developing symptoms, close contacts that had contact with a newly PCR positive case within 4 days should be judged as at risk of being infected;close contacts that had contact within 8 days of a newly symptomatic case should be judged as at risk being infected.

Characteristics of Lymphocyte Subsets and Cytokine Profiles of Patients with Coronavirus Disease 2019 (preprint)

Background: To explore the changes in lymphocyte subsets and cytokine profiles in patients with coronavirus disease 2019 (COVID-19) and their relationship with disease severity. Methods: This study included 228 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 1, 2020 to February 20, 2020. The characteristics of lymphocyte subsets and cytokine profiles of severe and mild COVID-19 patients were compared. Of the 228 patients enrolled, 48 were severe patients and 180 were mild patients. Results: Lymphocyte counts, absolute number of total T lymphocytes, CD4+T cells, CD8+T cells, and total B lymphocytes were significantly lower in severe patients (0.8×109/L, 424.5×106/L, 266×106/L, 145.5×106/L, 109.5×106/L, respectively) than in mild patients (1.2×109/L, 721×106/L, 439.5×106/L, 281.5×106/L, 135×106/L, respectively). A multivariate logistic regression analysis showed that age, C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for developing into severe condition. The lymphocyte subsets decreased and cytokine profiles increased more significantly in severe patients than in mild patients. Conclusions: CRP, NLR, and age may serve as powerful factors for early identification of severe patients.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial (preprint)

Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein (preprint)

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.