Health-Seeking Behavior of Patients with Cardiovascular Diseases During COVID-19 Epidemic and Post-Epidemic Period in Shanghai, China (preprint)

Background: The COVID-19 pandemic has led to concerns around its subsequent impact on patients with non-COVID-19 diseases, and the health-seeking behavior of such patients must be investigated.Methods: Taking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of hospital visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-epidemic (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019).Findings: Compared with those of the same period during pre-COVID years, the number of hospital visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level of the post-epidemic period. This decrease-rebound-fallback pattern was largely attributed to the dynamics of visits to community clinics rather than academic hospitals. The number of new COVID-19 cases or deaths announced on a given day correlated negatively with hospital visits during the same day and for the following 42 days, with the correlation at its most prominent at seven days. Hospital visit dynamics differed for various cardiovascular diseases. Whereas hospital visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, hospital visits for ST-segment elevated myocardial infarction did not fall during the lockdown period but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period.Interpretation: The health-seeking behavior of patients with cardiovascular diseases exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Hospital visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.Funding: Shanghai Hospital Development Center, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Commission, and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Declaration of Interest: All authors declare no conflicts of interest.Ethical Approval: This study was approved by the ethics committee at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

Molecular Characterization of the FCoV-like Canine Coronavirus HLJ-071 in China (preprint)

Background According to differences in antigens and genetic composition, canine coronavirus (CCoV) consists of two genotypes, CCoV-Ⅰ and CCoV-Ⅱ. Recently, CCoVs with mutant variations have been found to be pantropic and pathogenic in dogs.Results In this study, we isolated a CCoV, designated HLJ-071, from a dead 5-week-old female Welsh Corgi with severe diarrhea and vomiting. Sequence analysis suggested that HLJ-071 bears a complete ORF3abc when compared with classic CCoV isolates (1–71, K378 and S378). In addition, a variable region was located between the S gene and the open reading frames (ORF) 3a gene, in which HLJ-071 has a deletion of 104 nucleotides (nts) when compared with classic CCoV strains 1–71, S378 and K378. Phylogenetic analysis based on the S gene and complete sequences showed that HLJ-071 is closely related to Feline Coronavirus (FCoV) II. Recombination analysis suggested that HLJ-071 originated from the recombination of FCoV 79-1683, FCoV DF2 and CCoV A76. Finally, cell tropism experiments suggested that HLJ-071 is able to replicate in canine macrophages/monocytes.Conclusion The present study involved the isolation and genetic characterization of a variant CCoV strain. The spike protein and ORF3abc of CCoV might play a key role in viral tropism, which could affect replication in monocyte/macrophage cells. This will provide essential information for further understanding the evolution of CCoV in China.

Cell entry of SARS-CoV-2 conferred by angiotensin-converting enzyme 2 (ACE2) of different species (preprint)

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a huge threat to many countries around the world. However, where is it origin and which animals are sensitive to cross-species transmission is unclear. The interaction of virus and cell receptor is a key determinant of host range for the novel coronavirus. Angiotensin-converting enzyme 2 (ACE2) is demonstrated as the primary entry receptor for SARS-CoV-2. In this study, we evaluated the SARS-CoV-2 entry mediated by ACE2 of 11 different species of animals, and discovered that ACE2 of Rhinolophus sinicus (Chinese horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (pig), Capra hircus (goat) and especially Manis javanica (Malayan pangolin) were able to render SARS-CoV-2 entry in non-susceptible cells. This is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the presume that SARS-CoV-2 may have a pangolin origin. However, none of the ACE2 proteins from Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (chicken), Notechis scutatus (mainland tiger snake), Mus musculus (house mouse) rendered SARS-CoV-2 entry. Specifically, a natural isoform of Macaca mulatta (Rhesus monkey) ACE2 with a mutation of Y217N was resistance to infection, which rises the possible impact of this type of ACE2 during monkey studies of SARS-CoV-2. Overall, these results clarify that SARS-CoV-2 could engage receptors of multiple species of animals and it is a perplexed work to track SARS-CoV-2 origin and its intermediate hosts. IMPORTANCEIn this study, we illustrated that SARS-CoV-2 is able to engage receptors of multiple species of animals. This indicated that it may be a perplexed work to track SARS-CoV-2 origin and discover its intermediate hosts. This feature of virus is considered to potentiate its diverse cross-species transmissibility. Of note, here is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the possibility that SARS-CoV-2 may have a pangolin origin. And we also demonstrated that not all species of bat were sensitive to SARS-CoV-2 infection. At last, it is also important to detect the expression ratio of the Y217N ACE2 to the prototype in Rhesus monkeys to be recruited for studies on SARS-CoV-2 infection.