Search

Background: Estimation of the fraction and contagiousness of undocumented novel coronavirus (COVID-19) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Many mild infections are typically not reported and, depending on their contagiousness, may support stealth transmission and the spread of documented infection. Methods: Here we use observations of reported infection and spread within China in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with the emerging coronavirus, including the fraction of undocumented infections and their contagiousness. Results: We estimate 86% of all infections were undocumented (95% CI: [82%-90%]) prior to the Wuhan travel shutdown (January 23, 2020). Per person, these undocumented infections were 52% as contagious as documented infections ([44%-69%]) and were the source of infection for two-thirds of documented cases. Our estimate of the reproductive number (2.23; [1.77-3.00]) aligns with earlier findings; however, after travel restrictions and control measures were imposed this number falls considerably. Conclusions: A majority of COVID-19 infections were undocumented prior to implementation of control measures on January 23, and these undocumented infections substantially contributed to virus transmission. These findings explain the rapid geographic spread of COVID-19 and indicate containment of this virus will be particularly challenging. Our findings also indicate that heightened awareness of the outbreak, increased use of personal protective measures, and travel restriction have been associated with reductions of the overall force of infection; however, it is unclear whether this reduction will be sufficient to stem the virus spread.

The HLA-DM locus encodes class II-like A and B chains and apparently regulates the antigen presentation function of conventional major histocompatibility complex (MHC) class II molecules. Here we describe the HLA-DMB mutations in three presentation defective B lymphoblastoid cells lines (B-LCL), 7.19.6, 10.6.6, and 10.78.6, which express DMB transcripts of abnormal length. Mutant 7.19.6 has a C--T point mutation that introduces a 5' splice site into exon 3 of DMB. The independently derived mutants, 10.6.6 and 10.78.6, each harbor a G--A mutation in exon 3 and also lack an identical downstream segment of RNA. Mapping of DMB intron/exon borders, using a genomic clone, revealed that the segment missing in mutants 10.6.6 and 10.78.6 represents the fourth exon of DMB; no mutations were found within exon 4 in either 10.6.6 or 10.78.6, however. In addition, the DMB gene was found to have a six exon genomic structure, typical of MHC class II B genes.