Highlights d 1.6 million tests identified 1,388 SARS-CoV-2 infections in Guangdong by 19 March d Virus genomes can be recovered using a variety of sequencing approaches d Analyses reveal multiple viral importations with limited local transmission d Effective control measures helped reduce and eliminate chains of viral transmission

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Highlights: 1) 1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020; 2) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. 3) Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. 4) Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary: COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.

Objectives To understand persistence of the virus in body fluids and immune response of infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus disease 2019 (COVID-19). Methods We determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction (rRT-PCR), serum antibodies of IgA, IgG and IgM by enzyme linked immunosorbent assay (ELISA), and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China. Results We found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3×10 6 vs 6.4×10 4 , p<0.05; 7∼8w) and throat (6.9×10 6 vs 2.9×10 5 , p<0.05; 4∼5w), while comparable in sputum samples (5.5×10 6 vs 0.9×10 6 , p<0.05; 4∼5w). Viraemia was rarely detected (2.8%, n=1/35). We detected early seroconversion of IgA and IgG at 1 st week after illness onset (day 5, 5.7%, n=2/35). Neutralizing antibodies were produced in the second week, and observed in all 35 included cases after 3 rd week illness onset. The levels of neutralizing antibodies correlated with IgG (r s =0.85, p<0.05; kappa=0.85) and IgA (r s =0.64, p<0.05; kappa=0.61) in severe, but not mild cases (IgG, r s =0.42, kappa=0.33; IgA, r s =0.32, kappa=0.22). No correlation with IgM in either severe (r s =0.17, kappa=0.06) or mild cases (r s =0.27, kappa=0.15) was found. Conclusions We revealed a prolonged shedding of virus RNA in upper respiratory tract, and evaluated the consistency production of IgG, IgA, IgM and neutralizing antibodies in COVID-19 cases.

Spontaneous clearance of hepatitis C virus (HCV) occurs in 10–40% of the infections. Specific human leukocyte antigen (HLA) alleles have been identified in associating with HCV clearance. However, data on the association of HLA with the spontaneous clearance of HCV are scarce in the Chinese population. In the current study we studied the HLA class I and class II genes in 231 Chinese voluntary blood donors who had cleared HCV infection spontaneously compared to 429 subjects with chronic HCV infections. We also studied their IL28B SNP (rs8099917) genotype, since a number of investigators have found a strong association of IL28B with spontaneous or treatment induced HCV clearance. We found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR = 0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P = 0.005, respectively) were associated with HCV spontaneous clearance, independent of age, gender and IL28B polymorphism. We concluded that in the Chinese population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity to clear HCV independent of IL28B, which suggesting that the innate and adaptive immune responses both play an important role in the control of HCV.