Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.

Comparative study on virus shedding patterns in nasopharyngeal and fecal specimens of COVID-19 patients

Dear Editor,An acute viral pneumonia(COVID-19),caused by the novel coronavirus known as SARS-CoV-2,was first identified during December 2019 in China(Zhu et al.,2020).SARSCoV-2 was found to be highly transmissible in humans(Wang et al.,2020)and is now a pandemic spreading to over 140 countries and causing over 150,000 infections and 6,000 deaths as of March 15,2020.Diagnosis is critical for confirmation and treatment of COVID-19.Currently the primary criterion for diagnosis of COVID-19 is viral RNA detection for respiratory samples.Recently,two studies on virus loads in clinical samples reported that viral loads in nasal and throat swabs and sputum specimens peaked at 3–7 days after illness onset(d.a.o.)and virtually disappeared before 15 d.a.o.(Pan et al.,2020;Zou et al.,2020).Another study showed that the median duration of virus shedding in throat swabs was 20 d.a.o.in survivors and was detectable until death in non-survivors(Zhou et al.,2020).Additionally,live viruses have been isolated in the feces and urine samples of COVID-19 patients.However,the viral dynamics in these types of specimens has not yet been clearly elucidated,as well as comparative studies on virus shedding in the upper respiratory,intestinal,and urinary tracts.

Distinct durability of IgM/IgG antibody responses in COVID-19 patients with differing severity

Dear Editor,The coronavirus disease 2019(COVID-19)pandemic is generating a demand for simultaneous vaccine development,which is expected to prevent future outbreaks by eliciting sufficient and protective immunity.

Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges

Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).IAVs and CoVs both have broad host ranges and share multiple hosts.Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs,further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk.Moreover,SARS-CoV-2 may maintain longterm circulation in humans as seasonal IAVs.Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden.Herein,we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs,further affecting virus evolution and disease dynamics and burden,calling for active virus surveillance and countermeasures for future public health challenges.