Both Simulation and Sequencing Data Reveal Multiple SARS-CoV-2 Variants Coinfection in COVID-19 Pandemic (preprint)

SARS-CoV-2 is a single-stranded RNA betacoronavirus with a high mutation rate. The rapidly emerged SARS-CoV-2 variants could increase the transmissibility, aggravate the severity, and even fade the vaccine protection. Although the coinfections of SARS-CoV-2 with other respiratory pathogens have been reported, whether multiple SARS-CoV-2 variants coinfection exists remains controversial. This study collected 12,986 and 4,113 SARS-CoV-2 genomes from the GISAID database on May 11, 2020 (GISAID20May11) and April 1, 2021 (GISAID21Apr1), respectively. With the single-nucleotide variants (SNV) and network clique analysis, we constructed the single-nucleotide polymorphism (SNP) coexistence networks and noted the SNP number of the maximal clique as the coinfection index. The coinfection indices of GISAID20May11 and GISAID21Apr1 datasets were 16 and 34, respectively. Simulating the transmission routes and the mutation accumulations, we discovered the linear relationship between the coinfection index and the coinfected variant number. Based on the linear relationship, we deduced that the COVID-19 cases in the GISAID20May11 and GISAID21Apr1 datasets were coinfected with 2.20 and 3.42 SARS-CoV-2 variants on average. Additionally, we performed Nanopore sequencing on 42 COVID-19 patients to explore the virus mutational characteristics. We found the heterozygous SNPs in 41 COVID-19 cases, which support the coinfection of SARS-CoV-2 variants and challenge the accuracy of phylogenetic analysis. In conclusion, our findings reported the coinfection of SARS-CoV-2 variants in COVID-19 patients, demonstrated the increased coinfected variants number in the epidemic, and provided clues for the prolonged viral shedding and severe symptoms in some cases.

Epidemiology Characteristic and Co-infection Pattern of Pathogens in Patients With Respiratory Tract Infection in Southern China, 2018-2020. (preprint)

Background: Respiratory tract infections (RTIs) is the highest prevalent disease and southern china has a wide spectrum of respiratory pathogen. The aim of this work was to renew the epidemiology characteristics of respiratory pathogens found in children and adults with RTIs from 2018 to 2020 in southern China. Methods: In this work, a total of 134,552 nasopharyngeal or throat swabs (patients from 407 hospitals) were analyzed, and fourteen respiratory viruses (Influenza A virus, influenza B virus, parainfluenza viruses, respiratory syncytial virus, adenovirus, human rhinovirus, human metapneumovirus, human Coronavirus, human bocavirus, enterovirus, cytomegalovirus, herpes simplex virus, mycoplasma pneumoniae and chlamydia pneumoniae) were detected using PCR/RT-PCR. Result: The most common respiratory pathogens in southern china were ADV (16.19%), RSV (15.48%), RHV (11.51%), IAV (10.93%), MP (8.95%), EBV (8.70%), PIV (7.67%), IBV (5.44%), with IAV and ADV as the most prevalent pathogens in adults (11.68%) and children (17.10%) respectively. In detail, ADV (16.30%) and RSV (18.93%) are most common in 0-4 years old, with IAV (16.68%), ADV (20.36%) in 5-14 years old, with EBV (7.48%, 8.74%), IAV (15.43, 9.76%) in 15-49y, 50-64y and IAV (7.37%), IBV (2.43%) in 65-105y. Over three years witnessed an increase in PDR of PIV in 0-4y, 5-14y and 65-105y, and RHV in 5-14y and 15-49y. In month distribution, the positive detection rate of pathogens in adults were generally lower than that in children except for EBV and majority of pathogens has shown a sharp decline in 2020. In Upper RTIs, 77.27% (17/ 22) of co-infected patients had infection to ADV, with poly-infection to ADV and RHV the highest (8/22). In Lower RTIs, the ADV infected patients showed that its co-infection rate to MP, PIV, RHV or RSV were 19.51% (48/246), 15.45% (38/246), 14.63% (36/246) and 14.63% (36/246) respectively. Only IAV, IBV and EBV were detected in co-infection patients with lower RTIs. Conclusion: IAV and ADV were the most important respiratory pathogen in adults and children respectively in southern Chin and cross-reactivity might exist between ADV, RHV, PIV and MP. These should be taken into consideration when they formulate the strategies for co-infection avoidance in patients.

Rapid Screening Diagnosis of SARS-COV-2 Infection With IgM-igG Combined Antibody Test Using Peripheral Blood (preprint)

Background Rapid and convenient screening for identification of SARS-CoV-2 infected individuals are key to prevent and control this pandemic.Methods The peripheral blood samples were collected from coronavirus disease 2019 (COVID-19) patients and asymptomatic carriers to evaluate the test characteristics of the IgM-IgG combined assay for SARS-CoV-2 compared to that of serum samples and enzyme-linked immuno sorbent assay (ELISA). Close contacts, healthcare workers and workforces were recruited and screened using this assay.Results The sensitivity of the rapid IgM-IgG combined antibody test for SARS-CoV-2 using peripheral blood (sued as a POCT) was 97.0% and the specificity was 99.2%, which was consistent with the result obtained using serum sample (consistency is about 100%). Furthermore, this POCT assay also can detect IgM and IgG antibodies of SARS-CoV‐2 in asymptomatic carriers, with 19 of the 20 RT-PCR confirmed asymptomatic carriers testing positive. Therefore, this POCT assay was used for population screening of SARS-CoV-2 infection diagnosis. First, it found 4 positive close contacts among the 10 cases, and there were three IgM positive cases and one IgG positive case among them. It is worth noting that the IgM positive cases also tested positive for the nucleic acid of the SARS-CoV-2. Second, there was one IgM positive assay among the 63 healthcare workers, but RT-PCR of SARS CoV-2 was negative. Third, for workforces screening, there were no positive cases.Conclusions The IgM-IgG combined antibody test of SARS-CoV-2 can be used as a POCT for rapid screening of SARS-CoV-2 infection.

Comparison of clinical characteristics and risk factors in hospitalized patients with SARS-CoV-2, MERS-CoV, and SARS-CoV infection (preprint)

Herein, we compared the risk factors, clinical presentation of patients hospitalized with SARS-CoV-2, SARS-CoV, or MERS-CoV infection. Our data sources include PubMed, Embase, CNKI, and Ovid/Medline. The proportion of male patients with COVID-19 was higher than who with SARS but lower than who with MERS (p<0.001). More patients with COVID-19 had coexisting chronic medical conditions than those with SARS (p<0.001) but fewer than those with MERS (p<0.001), and the prevalence of hypertension (17%) and smoking history (14%) was higher than in patients with SARS (p<0.001). Furthermore, the symptom of fever (53%), hemoptysis (1%), diarrhea (4%) and vomiting (3%) of COVID-19 were significantly lower than that in patients with SARS or MERS. The level of ALT and AST in COVID-19 was significantly lower (p<0.001), however, thrombocytopenia, high LDH were common. Summary, male, smoking history and hypertension were the most common risk factors for hospitalization with COVID-19; and the clinical feature was less severe in COVID-19.

CovProfile: profiling the viral genome and gene expressions of SARS-COV2 (preprint)

The SARS-CoV-2 virus has infected more than one million people worldwide to date. Knowing its genome and gene expressions is essential to understand the virus mechanism. Here, we propose a computational tool CovProfile to detect the viral genomic variations as well as viral gene expressions from the sequences obtained from Nanopore devices. We applied CovProfile to 11 samples, each from a terminally ill patient, and discovered that all the patients are infected by multiple viral strains, which might affect the reliability of phylogenetic analysis. Moreover, the expression of viral genes ORF1ab gene, S gene, M gene, and N gene are high among most of the samples. While performing the tests, we noticed a consistent abundance of transcript segments of MUC5B, presumably from the host, across all the samples.

Comparison of clinical characteristics and risk factors in hospitalized patients with SARS-CoV-2, MERS-CoV, and SARS-CoV infection (preprint)

Herein, we compared the risk factors, clinical presentation of patients hospitalized with SARS-CoV-2, SARS-CoV, or MERS-CoV infection. The proportion of male patients with COVID-19 was higher than who with SARS but lower than who with MERS (p<0.001). More patients with COVID-19 had coexisting chronic medical conditions than those with SARS (p<0.001) but fewer than those with MERS (p<0.001), and the prevalence of hypertension (17%) and smoking history (14%) was higher than in patients with SARS (p<0.001). Furthermore,the symptom of fever (53%), hemoptysis (1%), diarrhea (4%) and vomiting (3%) of COVID-19 were significantly lower than that in patients with SARS or MERS. The level of ALT and AST in COVID-19 was significantly lower (p<0.001), however, thrombocytopenia, high LDH were common. Summary, male, smoking history and hypertension were the most common risk factors for hospitalization with COVID-19; and the clinical feature was less severe in COVID-19.