Plasma cell-free DNA promise disease monitoring and tissue injury assessment of COVID-19 (preprint)

COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.

Genomic epidemiology of SARS-CoV-2 in the United Arab Emirates reveals novel virus mutation, patterns of co-infection and tissue specific host responses (preprint)

Background: The United Arab Emirates is a major business hub with substantial amount of international travel. Like many other countries, it was greatly affected by the COVID-19 pandemic since late January 2020, with recurring waves of infection. This study aimed at combining genomic and epidemiological data to unravel the source of SARS-CoV-2 introduction, transmission and evolution in the country. Methods: We performed meta-transcriptomic sequencing of 1,067 nasopharyngeal swab samples collected from qRT-PCR positive COVID-19 patients in Abu Dhabi, UAE, between May 9th and June 29th 2020. We investigated the genetic diversity and transmission dynamics of the viral population and analyzed the infection and transmission potential of novel genomic clusters. Within-host SARS-CoV-2 genetic variation was analyzed to determine the occurrence and prevalence of multiple infections. Finally, we evaluated innate host responses during the prolonged period of local infection. Results: All globally known SARS-CoV-2 clades were identified within the UAE sequenced strains, with a higher occurrence of European and East Asian clades. We defined 5 subclades based on 11 unique genetic variants within the UAE strains, which were associated with no significantly different viral loads. Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously observed in the bronchoalveolar lavage fluid samples. This observation is accompanied with an upregulation of APOBEC4, an under-studied putative cytidine-uridine editing enzyme in the infected nasopharynx. Conclusions: The genomic epidemiological and molecular biological knowledge obtained in the study provides new insights for the SARS-CoV-2 evolution and transmission. We highlight the importance of sustained surveillance of the virus mutation using genomic sequencing as a public health strategy. Keywords: SARS-CoV-2, meta-transcriptomic sequencing, novel mutations and subclades, co-infection, cyosine depletion, host RNA editing

Kidney manifestations of mild, moderate and severe coronavirus disease 2019: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 3 million patients globally. Previous data from Wuhan city showed that acute kidney injury (AKI), proteinuria and hematuria occurred frequently in patients with severe COVID-19. However, the prevalence of kidney injury in milder cases remains unclear. METHODS: This retrospective study included two major consecutive cohorts of COVID-19 patients in Sichuan Province. Baseline characteristics, laboratory data including renal function, proteinuria and dipstick hematuria, and other laboratory parameters were collected. A subgroup of patients was followed up for 2-4 weeks to evaluate the short-term outcome of renal impairment. RESULTS: Overall, 168 COVID-19-positive patients were included in the study. The majority of patients (79.7%) were diagnosed with mild or moderate disease. Half of patients presented with fever; however, in The Tibetan cohort, fever only occurred in 13.4% of patients. On hospital admission, proteinuria and dipstick hematuria were noted in 18.4% and 17.4% of patients, respectively, while AKI only occurred in one patient. Further analysis showed that severe or critical COVID-19 was associated with higher risk of proteinuria [relative risk (RR) 7.37, 95% confidence interval (CI) 2.45-22.18, P = 3.8 × 10-4] and dipstick hematuria (RR 8.30, 95% CI 2.69-25.56, P = 2.3 × 10-4). Proteinuria, dipstick hematuria, or the combination of proteinuria and hematuria could significantly predict severe or critical severe COVID-19. CONCLUSIONS: Proteinuria and dipstick hematuria are not uncommon in patients with COVID-19 infection, especially in severe or critical cases.

Genomic Epidemiology of SARS-CoV-2 in the United Arab Emirates Reveals Novel Insights into the Virus Mutation, Co-Infection and Host-Dependent RNA Editing (preprint)

Background: The United Arab Emirates is a major business hub with substantial amount of international travel. Like many other countries, it was greatly affected by the COVID-19 pandemic since late January 2020, with recurring waves of infection. This study aimed at combining genomic and epidemiological data to unravel the source of SARS-CoV-2 introduction, transmission and evolution in the country.Methods: We performed meta-transcriptomic sequencing of 1,067 nasopharyngeal swab samples collected from qRT-PCR positive COVID-19 patients in Abu Dhabi, UAE, between May 9th and June 29th 2020. We investigated the genetic diversity and transmission dynamics of the viral population and analyzed the infection and transmission potential of novel genomic clusters. Within-host SARS-CoV-2 genetic variation was analyzed to determine the occurrence and prevalence of multiple infections. Finally, we evaluated innate host responses during the prolonged period of local infection.Findings: All globally known SARS-CoV-2 clades were identified within the UAE sequenced strains, with a higher occurrence of European and East Asian clades. We defined 5 subclades based on 11 unique genetic variants within the UAE strains, which were associated with higher viral loads (p<0.001). Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also observed a host-defense mechanism via RNA editing, likely mediated by APOBEC3 rather than ADAR in nasopharyngeal samples.Interpretation: The SARS-CoV-2 epidemic in the UAE was founded by international importation followed by local transmission, leading to prevalent multiple infection and large subclade descendances. While RNA editing mechanisms mutate the viral population, newly arisen genetic variation can contribute to a heavier viral burden. Meta-transcriptomic sequencing can help to determine the transmission patterns of SARS-CoV-2.Funding: Department of Health of Abu Dhabi, UAE and National Natural Science Foundation of China.Declaration of Interests: None to declareEthics Approval Statement: The study was approved by the Abu Dhabi COVID19 Research IRB Committee (approval number DOH/CVDC/2020/1945).

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019 (preprint)

Background The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a six-month follow-up of functional status of COVID-19 survivors.Methods We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a six-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 5 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a six-month follow-up after discharge.Results We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At six-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95%CI 1.33 - 12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95%CI 1.06 - 10.81, p = 0.039).Conclusions A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a six-month follow-up; intervention strategies are required.