COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old: A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China. (preprint)

Objective: This study attempted to explore the difference of clinical characteristics in H1N1 influenza infection and SARS-CoV-2 Omicron infection in people younger than 65 years old, in order to better identify the two diseases. Methods: A total of 127 H1N1 influenza patients diagnosed from May 2009 to July 2009 and 3265 patients diagnosed and identified as SARS-CoV-2 Omicron BA.2 variant from March 2022 to May 2022 were admitted in this study. Through the 1 : 2 match based on age (The difference is less than 2 years), gender and underlying diseases115 patients with H1N1 infection and 230 patients with SARS-CoV-2 Omicron BA.2 infection (referred to as H1N1 group and Omicron group) were included in the statistics. The clinical manifestations of H1N1 group were compared with those of Omicron group. Logistic regression was performed to analyze the possible independent risk factors of H1N1 group and Omicron group. And multiple linear regression was used to analyze the factors for time for nucleic acid negativization (NAN) . Results: The median age of the two groups was 21 [11,26] years. Compared with the H1N1 group, the Omicron group had lower white blood cell count and CRP levels, less fever, nasal congestion, sore throat, cough, sputum and headache, while more olfactory loss, muscle soreness and LDH abnormalities. The Omicron group used less antibiotics and antiviral drugs, and the NAN time was longer (17 [ 14,20] VS 4 [ 3,5], P < 0.001). After logistic regression, it was found that fever, cough, headache, and increased white blood cell count were more correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more correlated with the Omicron group. After analyzing the factors of NAN time, it was found that fever (B 1.529, 95 % CI [0.149,2.909], P = 0.030) significantly predicted longer NAN time in Omicron patients. Conclusion: This study comprehensively evaluated the similarities and differences in clinical characteristics between SARS-CoV-2 Omicron infection and 2009 H1N1 influenza infection, which is of great significance for a better understanding for these diseases.

The effects of vaccination on the disease severity and factors for viral clearance and hospitalization in Omicron-infected patients :A retrospective observational cohort study from recent regional outbreaks in China (preprint)

ABSTRACT Object It remains unelucidated regarding the effects of vaccination on disease severity and factors for viral clearance and hospitalization in omicron-infected patients. Methods The clinical manifestations of 3,265 Omicron-infected patients (BA.2 variant; the Omicron group) were compared with those of 226 Delta-infected patients (the Delta group).A Multi-class logistic regression model was employed to analyze the impacts of vaccination doses and intervals on disease severity; a logistic regression model to evaluate the risk factors for hospitalization; R 4.1.2 data analysis to investigate the factors for time for nucleic acid negativization (NAN). Results Compared with the Delta group, the Omicron group reported a fast transmission, mild symptoms, and lower severity incidence, and a significant inverse correlation of vaccination dose with clinical severity (OR: 0.803, 95%CI: 0.742-0.868, p<0.001). Of the 7 or 5 categories of vaccination status, the risk of severity significantly decreased only at ≥21 days after three doses (OR: 0.618, 95% CI: 0.475-0.803, p<0.001; OR: 0.627, 95% CI: 0.482-0.815, p<0.001, respectively). The Omicron group also reported underlying illness as an independent factor for hospitalization, sore throat as a protective factor, and much shorter time for NAN [15 (12,19) vs. 16 (12,22), p<0.05]. NAN was associated positively with age, female gender, fever, cough, and disease severity, but negatively with vaccination doses. Conclusion Booster vaccination should be advocated for COVID-19 pandemic-related control and prevention policies and adequate precautions should be taken for patients with underlying conditions.

A need of COVID19 vaccination for children aged <12 years: Comparative evidence from the clinical characteristics in patients during a recent Delta surge (B.1.617.2) (preprint)

Objective: To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics in unvaccinated children aged < 12 y with vaccinated patients aged > 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods: A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Realtime PCR positive and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged > 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared;the effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results: The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged; 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84(1.32,2.71)x 10^9/L vs. 1.31(0.94,1.85)x 10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28(3.31,8.13) vs. 9.10(4.37,15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13(0.00,0.09) vs. 0.12(0.03,0.41), p<0.05; 0.02(0.00,0.14) vs. 1.94(0.54,6.40), p <0.05; 5.46(2.41,9.26) vs. 73.63 (54.63,86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Conclusion: Children aged < 12y may be critical hidden spreaders, which indicates an urgent need of vaccination for this particular population.

Successful Treatment of Convalescent Plasma Therapy in Three Patients With Severe SARS-CoV-2 Infection in Fuzhou, China (preprint)

Background Up to now, there is no specific treatment for coronavirus disease 2019 (COVID-19) yet except for general supportive care. Hence, it will be critical to find a new strategy for COVID-19. The study is to explore whether convalescent plasma transfusion may be beneficial in the treatment of severe patients with COVID-19.Methods This is a retrospective analysis of three severe patients with laboratory-confirmed COVID-19 and admitted in Fuzhou pulmonary hospital of Fujian province from February 18th, to May 15th,who met the following criteria: (1) within 3 weeks of symptom onset；laboratory confirmed cases or who had viremia conformed by clinical experts；（2）Severe patients with rapidly progress or the early stage of critically ill patients or who required plasma therapy were comprehensively evaluated by clinical experts. The data of clinical manifestations and the progresses of disease monitored by blood-gas analysis, biochemical tests, routine examine, radiological exam were abstracted and then analysis the changes before and after convalescent plasma transfusion. Results All three patients (one male and two females; age range, 57-65years) were treated with convalescent plasma during the study. Two patients had underlying chronic diseases, including diabetes and hypertension. The most common symptoms were fever (three cases, 3/3) and cough (two cases, 2/3). All patients were treated with a combination of two antiviral drugs (lopinaviritonavir or arbidol combined with IFN-ɑ), whereas none of the patients were given glucocorticoids. Following plasma transfusion, the symptoms of the whole group improved to some degree, mainly manifested as reducing in coughing and body temperature normalized. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.97 × 109/L vs. 1.08 × 109/L) and decreased IL-6 (41.34 pg/ml vs. 13.83 pg/ml). The density of bilateral infiltration on CT imaging showed varying degrees of absorption within 7days. Throat swab nucleic acid test of most patients became negative for the novel coronavirus within 3 days after the transfusion. No adverse effects and severe complications were observed. Conclusions In this preliminary uncontrolled case series of 3severe patients with COVID-19, convalescent plasma could be as a promising therapy for COVID-19 without corticosteroids and no serious adverse reactions associated with the transfusion of convalescent plasma were observed, which would improve the clinical outcomes following by improvement in their clinical status. Using the convalescent plasma at the early stage(less than 10 days) of disease could be more effective. Anticoagulation is necessary for severe patients with COVID-19 given the state of hypercoagulability. However, given the small sample size and limited study design, naturally these results should be taken with a grain of salt until replicated by other further investigation in larger well-controlled trials.

Evaluation on the Diagnostic Efficiency of Different Methods in Detecting COVID-19. (preprint)

Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19.Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. EPlex: pooled sensitivity was 0.94; specificity 1.0; PLR 90.91; NLR 0.07; DOR 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity 0.98; PLR 42.46; NLR 0.02; DOR 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity 0.97; PLR 26.67; NLR 0.01; DOR 3100.93; AUC=0.9970, Q*=0.9800. Cobas®: pooled sensitivity was 0.99; specificity 0.96; PLR 37.82; NLR 0.02; DOR 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity 0.99; PLR 36.22; NLR 0.04; DOR 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity 0.97; PLR 27.44; NLR 0.01; DOR 3488.15; AUC=0.9977, Q*=0.9829.Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas®, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.

Evaluation on the diagnostic efficiency of different methods in detecting COVID-19. (preprint)

Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19 to provide preliminary evidence on choosing favourable method for COVID-19 detection. Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. The results showed no significant threshold exist. EPlex: pooled sensitivity was 0.94; specificity was 1.0; PLR was 90.91; NLR was 0.07; DOR was 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity was 0.98; PLR was 42.46; NLR was 0.02; DOR was 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity was 0.97; PLR was 26.67; NLR was 0.01; DOR was 3100.93; AUC=0.9970, Q*=0.9800. Cobas: pooled sensitivity was 0.99; specificity was 0.96; PLR was 37.82; NLR was 0.02; DOR was 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity was 0.99; PLR was 36.22; NLR was 0.04; DOR was 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity was 0.97; PLR was 27.44; NLR was 0.01; DOR was 3488.15; AUC=0.9977, Q*=0.9829. Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.

The Chest CT Features of Coronavirus Disease 2019 (COVID-19) in China: A Meta-analysis of 19 Trials (preprint)

ObjectiveThis study aimed to summarize the characteristics of chest CT imaging in Chinese patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine. MethodsPubMed, Embase and Web of Science databases were thoroughly searched to identified relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R software version i386 4.0.0. Random-effects models were employed to calculate pooled mean differences. Results19 trials incorporating 1332 cases were included in the study. The results demonstrated that the incidence of ground-glass opacities (GGO) was 0.79, consolidation was 0.34; mixed GGO and consolidation was 0.46; air bronchogram sign was 0.41; crazy paving pattern was 0.32; interlobular septal thickening was 0.55; reticulation was 0.30; bronchial wall thickening was 0.24; vascular enlargement was 0.74. subpleural linear opacity was 0.28; intrathoracic lymph node enlargement was 0.03; pleural effusions was 0.03. The distribution in lung: the incidence of central was 0.05; peripheral was 0.74; peripheral involving central was 0.38; diffuse was 0.19; unifocal involvement was 0.09; multifocal involvement was 0.57; unilateral was 0.16; bilateral was 0.83; The incidence of lobes involved (>2) was 0.70; lobes involved ([less double equals]2) was 0.35. ConclusionGGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19. Peripheral, bilateral, involved lobes >2 might be the features of COVID-19 in the distribution aspect. Therefore, based on the aboved features of COVID-19 in chest CT imaging, it might be a promising means for identifying COVID-19.

Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19 (preprint)

Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed a distinct feature of adaptive immunity in severely affected patients, the coincidence of impaired cellular and enhanced humoral immune responses, suggesting that dysregulated adaptive immune responses advanced severe COVID-19. Excessive activation and exhaustion were observed in CD8 T effector cells, which might contribute to the lymphopenia. Interestingly, expression of Prothymosin alpha (PTMA), the proprotein of Tα1, was significantly increased in a group of CD8 T memory stem cells, but not in excessively activated T cells. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.