Bioinformatics and systematic biology methods to determine the pathogenic link between COVID-19 and atrial fibrillation (preprint)

The coronavirus disease 2019 (COVID-19) epidemic has not been effectively controlled thus far. Atrial fibrillation (AF) is a risk factor for COVID-19, and if not controlled in a timely manner, it will cause a catastrophic situation. However, the molecular mechanism of AF and COVID-19 is not well understood. We performed transcriptome analysis to capture common signaling pathways and molecular markers of AF and COVID-19, which will help in understanding the link between COVID-19 and AF. Three AF datasets (GSE41177, GSE31821, GSE79768) and one COVID-19 dataset (GSE147507) from the Gene Expression Omnibus (GEO) database were used in this study. Differential expression analysis of the datasets identified differential genes common to both diseases. To explore the biological mechanisms of the differential genes, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), protein-protein interaction (PPI), receiver operating characteristic curve (ROC), miRNA- transcriptionfactor (TF)-mRNA network, drug candidate prediction, molecular docking, and gene-disease association analyses were performed. We finally found 63 DEGs common to COVID-19 and AF. GO/KEGG allowed the common biological functions and signaling pathways of both diseases to be understood. Based on the PPI network, 5 hub genes (FCGR3B, IL1B, CXCR4, CSF2RB, and SELL) were identified, with CXCR4 as the most diagnostic and therapeutic target gene. Based on CXCR4, a miRNA-TF-mRNA network was constructed. Five potential therapeutic agents closely related to CXCR4 were identified, and their reliability was verified by molecular docking. Finally, possible associated diseases were analyzed. Taken together, our findings will help scholars understand the potential biological mechanisms between COVID-19 and AF. The development of precise therapeutic agents targeting CXCR4 is of great significance for COVID-19 patients with a history of AF.

Incidence, characteristics, risk factors, and outcomes of diabetic ketoacidosis in COVID-19 patients without prior insulin dependence: comparison with influenza (preprint)

Whether SARS-CoV-2 infection triggers diabetic ketoacidosis (DKA) is unclear. This study characterized incidence, patient profiles, risk factors, and outcomes of in-hospital DKA in COVID-19 patients without prior insulin dependence and compared with influenza. This cohort consisted of 13,383 hospitalized COVID-19 patients (March 2020 to July 2022) and 19,165 hospitalized influenza patients (January 2018 to July 2022) in Bronx, NY. Patients with prior DKA and prior insulin use were excluded. Primary outcomes were in-hospital mortality and new-insulin use 3-month post-infection. The incidence of DKA in hospitalized COVID-19 patients was significantly higher than hospitalized influenza patients (1.4% vs. 0.8%, p < 0.05). COVID-19 patients with DKA were more likely to be intubated, receive steroid treatment, and die (mortality OR = 6.178, p < 0.05) than those without DKA. DKA patients without pre-existing diabetes were more likely to die than DKA patients with pre-existing diabetes (OR = 7.56, p < 0.05). Steroid use, pre-existing type-2 diabetes, and male sex were risk factors for DKA. Patients with DKA had a higher rate of insulin use 3 months post SARS-CoV-2 infection compared to those without DKA (8.2% vs. 1.6%, p < 0.05), suggesting SARS-CoV-2 infection could trigger new insulin dependence. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants (preprint)

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Patient Self-Report Superior to Electronic Medical Record Abstraction for Identifying Positive COVID-19 Symptoms at Illness Onset

Introduction Most initial COVID-19 research focused on hospitalized patients. Presenting symptomatology in the outpatient setting was poorly characterized, making it difficult for primary care physicians to predict which patients would require hospitalization. Purpose To characterize presenting symptoms of COVID-19 infection and baseline patient characteristics and evaluate for correlation with disease severity, duration, and chronicity in the outpatient setting. Methods 107 adult, English speaking patients with suspected and confirmed COVID-19 cases at the three primary care practices of Stony Brook University Hospital were studied between March and December, 2020. Survey data was collected from patient telephone interviews and electronic medical record (EMR) ion. Potential risk factors assessed included participant demographics, medical comorbidities, and number and type of symptoms at illness onset. Outcome measures included symptom duration, hospitalizations, and persistence of symptoms at 12 weeks from study enrollment. Results Patient self-report survey elicited nearly twice as many symptoms described at illness onset vs. those recorded in the EMR (p<0.0001). Higher number of symptoms at illness onset was positively associated with symptom duration and chronicity. The presence of fever and hypoxia at the onset of illness were each positively associated with eventual hospitalization for COVID-19 disease. Conclusions Early in the setting of newly emerging infectious diseases, particularly those such as COVID-19 which involve multiple organ systems, patient self-report of symptoms using a complete review of systems, rather than EMR ion alone, may be key for accurate disease identification and characterization as well as prediction of eventual disease severity, duration and chronicity.

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants (preprint)

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial (preprint)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2 (preprint)

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

In-Hospital Rehabilitation and Functional Status of Non-Critically ill COVID- 19 Survivors (preprint)

This study investigated in-hospital rehabilitation and functional status at discharge of non-critically ill COVID-19 survivors with respect to pre-admission dependency status, discharge durable medical equipment, discharge medical follow-up recommendation, hospitalization duration, demographics, comorbidities, laboratory tests, and vital signs at hospital discharge. Comparisons were made between COVID-19 survivors who received rehab (N=155) and those who did not (N=162). Functional scores were obtained using the “Mental Status”, ICU Mobility, and modified Barthel Index scores at hospital discharge. Relative to the non-rehab patients, rehab patients were older, had more comorbidities, had worse pre-admission dependency status (p<0.05), were discharged with more assistive equipment and supplemental oxygen (p<0.001), spent more days in the hospital (p<0.001), had more follow-up referrals (p<0.05) with cardiology, vascular medicine, urology, and endocrinology being the top referrals, and had more secondary in-hospital diagnosis of AKI and acute respiratory failure. Functional scores of non-critically ill COVID-19 survivors were impaired at discharge and were associated with pre-admission dependency. Some functional scores were negatively correlated with age, hypertension, coronary artery disease, chronic kidney disease, psychiatric disease, anemia, and neurological disorders (p<0.05). These findings warrant follow up of COVID-19 survivors as many survivors will likely have significant post-acute COVID-19 sequela.

Functional Status of Mechanically Ventilated COVID-19 Survivors at ICU and Hospital Discharge (preprint)

Background A significant number of COVID-19 patients have been treated using invasive mechanical ventilation (IMV). The ability to evaluate functional status of COVID-19 survivors early on at ICU and hospital discharge can help minimize ICU-acquired weakness, promote rapid functional recovery, and improve quality of lifeMethods The modified “Mental Status”, ICU Mobility, and Barthel Index scores at ICU and hospital discharge were tabulated for 118 COVID-19 survivors treated with invasive mechanical ventilation (IMV). These functional scores were compared with pre-admission functional status, discharge durable medical equipment, discharge medical follow-up recommendation, duration on IMV, duration post IMV, demographics, comorbidities, laboratory tests, and vital signs at ICU and hospital discharge.  Results The majority of COVID-19 IMV patients were not functionally independent at hospital discharge (22% discharged with cane or rolling walker, 49% discharged with durable medical equipment, and 14% admitted to a rehabilitation facility), although they were prior to COVID-19 illness. Half of the patients were discharged with supplemental oxygen equipment. The most prevalent medical follow-up recommendations were cardiology, vascular medicine, pulmonology, endocrinology, and neurology with many patients receiving multiple medical follow-up recommendations. Functional status improved from ICU discharge to hospital discharge (p<0.001). Worse functional status at hospital discharge was associated with longer IMV duration, older age, male sex, higher number of comorbidities, and the presence of pre-existing comorbidities including hypertension, diabetes, chronic obstructive pulmonary disease, and immunosuppression (p<0.05, ANOVA). Conclusions The majority of IMV COVID-19 survivors were not functionally independent at discharge and required significant follow-up medical care. The COVID-19 circumstance has placed constraints on access to in-hospital rehabilitation. These findings underscore the need for prospective studies to ascertain the short- and long-term sequela in COVID-19 survivors. 

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development (preprint)

To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

Further Evaluation of the Mother-to-Child Transmission Potential of SARS-CoV-2 Infection During Pregnancy: A Retrospective Study (preprint)

Background. This study aimed to comprehensively evaluate the clinical characteristics of COVID-19 in perinatal period, and systematically assess the mother-to-child transmission potential of SARS-CoV-2Methods. We retrospectively analyzed the data of 23 pregnant patients in late pregnancy. Clinical specimens, including maternal and neonatal throat swabs, vaginal secretions, placenta tissues, and breast milk, were collected for the nucleic acid test of the virus. Pregnancy outcomes and neonatal results were also analyzed.Results. Overall, 10 patients (43.5%) had no symptoms and were found by routine chest CT. Complications appeared after COVID-19 onset included PROM (17.4%) and fetal distress (4.3%). Typical signs of viral pneumonia were recorded in chest CT of all patients. No patients developed severe pneumonia or died of COVID-19. All of 25 neonates were born alive. No severe asphyxia or neonatal death was observed. Although three neonates were tested transiently suspected positive for SARS-CoV-2 after being transferred to neonatology department, no newborns developed COVID-19. Out of various clinical specimens tested, only a rectal swab sample from one pregnant patient was tested positive for SARS-CoV-2, while all the other specimens including first sample of newborn throat swabs were negative. Pathological examination found no obvious chorioamnionitis or clear virus inclusion body in placenta, and ACE2 (angiotension-converting enzyme 2) was expressed at a moderate level.Conclusions. As in the general population of COVID-19, asymptomatic patients were present in pregnant women. There is no confirmatory evidence for mother-to-child transmission in COVID-19 patients with late pregnancy.

Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus (preprint)

The transcriptional response in Vero cells (ATCC(R) CCL-81) infected with the coronavirus Porcine Epidemic Diarrhea Virus (PEDV) was measured by RNAseq analysis 4 and 6 hours after infection. Differential expressed genes (DEGs) in PEDV infected cells were compared to DEGs responding in Vero cells infected with Mammalian Orthoreovirus (MRV). Functional analysis of MRV and PEDV DEGs showed that MRV increased the expression level of several cytokines and chemokines (e.g. IL6, CXCL10, IL1A, CXCL8 [alias IL8]) and antiviral genes (e.g. IFI44, IFIT1, MX1, OASL), whereas for PEDV no enhanced expression was observed for these "hallmark" antiviral and immune effector genes. Pathway and Gene Ontology "enrichment analysis" revealed that PEDV infection did not stimulate expression of genes able to activate an acquired immune response, whereas MRV did so within 6h. Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). PEDV also down-regulated expression of Ectodysplasin A, a cytokine of the TNF-family able to activate the canonical NFKB-pathway responsible for transcription of inflammatory genes like IL1B, TNF, CXCL8 and PTGS2. The only 2 cytokine genes found up-regulated by PEDV were Cardiotrophin-1, an IL6-type cytokine with pleiotropic functions on different tissues and types of cells, and Endothelin 2, a neuroactive peptide with vasoconstrictive properties. Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and "synaptic clefts" between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The information in this study describing a "very early" response of epithelial cells to an infection with a coronavirus may provide pharmacologists, immunological and medical specialists additional insights in the underlying mechanisms of coronavirus associated severe clinical symptoms including those induced by SARS-CoV-2. This may help them to fine-tune therapeutic treatments and apply specific approved drugs to treat COVID-19 patients.

China Neighborhood and Village Committee confront the COVID-19 Pandemic；Cultural History and Tracking back Review of Relevant Public Health Events in Last Century (preprint)

Managing epidemics need to unite each individual of the nations. Lockdown is an essential strategy to fatal and threatening epidemic. All of the citizens should realize that each of people has a responsibility to support the public health crisis. How to organize individual to fight against the epidemic plaque depends each of them. This essay discussed the COVID-19 pandemic relevant self-governance of community from a historical perspective in China. Self-governance of neighborhood committee and community residential office in urban and rural helped to control the COVID-19 pandemic in the communities in China. Co-operation and collective responsibility of citizens and community support is a critical condition to prevent epidemic. The community self-governance can track back Qin Dynasty in China history. It established baojia system to maintain social control for thousand years. Now, the community-based system, baojia system is becoming more autonomous for local citizenship and socialized governance in China. We reviewed a historical pneumonia plaque in North China in 1911. Chinese doctor, Wu Lien-teh (伍連德) confronted the epidemic crisis with many measures such as lockdown, quarantine, the wearing of mask, setup mobile hospitals, travel restriction, the cremation of victims, and border control. Dr. Wu made effort to establish the modern public health service in China. We think that the combination of culture background of China community with modern public healthcare system determinedly played important role to control the COVID-19 pandemic.

Characterization of Codon Usage Pattern in SARS-CoV-2 (preprint)

The outbreak of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed significant threats to international health. The genetic traits as well as evolutionary processes in this novel coronavirus are not fully characterized, and their roles in viral pathogenesis are yet largely unknown. To get a better picture of the codon architecture of this newly emerging coronavirus, in this study we perform bioinformatic analysis, based on publicly available nucleotide sequences of SARS-CoV-2 along with those of other members of human coronaviruses as well as non-human coronaviruses in different hosts, to take a snapshot of the genome-wide codon usage pattern of SARS-CoV-2 and uncover that all over-represented codons end with A/U and this newly emerging coronavirus has a relatively low codon usage bias, which is shaped by both mutation pressure and natural selection. Additionally, there is slight variation in the codon usage pattern among the SARS-CoV-2 isolates from different geo-locations. Furthermore, the overall codon usage pattern of SARS-CoV-2 is generally similar to that of its phylogenetic relatives among non-human betacoronaviruses such as RaTG13. Taken together, we comprehensively analyze the characteristics of codon usage pattern in SARS-CoV-2 via bioinformatic approaches. The information from this research may not only be helpful to get new insights into the evolution of SARS-CoV-2, but also have potential value for developing coronavirus vaccines.

Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients (preprint)

Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.

Characterization of codon usage pattern in novel coronavirus 2019-nCoV (preprint)

The outbreak of viral pneumonia in China due to a novel coronavirus 2019-nCoV poses significant threats to international health. In this study we perform bioinformatic analysis to take a snapshot of the codon usage pattern of 2019-nCoV and uncover that this novel coronavirus has a relatively low codon usage bias. The information from this research may not only be helpful to get new insights into the evolution of 2019-nCoV, but also have potential value for developing coronavirus vaccines.