Finding the Correlation between COVID-19 and Influenza Obscured by Seasonal Patterns: A Mathematical Modelling Study (preprint)

Background: Although significant seasonality had been reported among common human coronaviruses (NL63, 229E, HKU1, and OC43) and influenza viruses (IVA and IVB), the potential seasonal pattern of coronavirus disease 2019 (COVID-19) transmission and its interaction with winter influenza remains to be seen. Understanding the seasonality of and correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses may contribute to the prevention and control of the COVID-19 pandemic in the coming flu season.Methods: We used time series decomposition to separate the seasonal factors of four common human coronaviruses and two influenza viruses in the United States from 2014 to 2020. Test results and confirmed time series in the United States from the 14th to 45th weeks of 2020 were used to analyse the seasonality of SARS-CoV-2. We tried to eliminate the seasonality of SARS-CoV-2 by applying the average seasonal factors of the other beta-coronaviruses. After seasonal adjustment, we identified a correlation between COVID-19 and influenza. Additionally, we collected and analysed the weekly percent positive of influenza virus cases in nine census divisions in the United States between the 1st and 45th weeks of 2020, and the same period in 2016-2019, to verify this correlation.Findings: We identified a moderate correlation between betacoronaviruses and influenza viruses from 2014-2020. The seasonally adjusted Spearman correlation coefficient between coronavirus OC43 and influenza A virus (IVA) was 0.39, and 0.41 between coronavirus HKU1 and influenza B virus (IVB), while no similar relationship was identified between alphacoronaviruses and influenza viruses. The seasonally adjusted Spearman correlation coefficient between SARS-CoV-2 and influenza viruses among nine census divisions in the United States from the 14th to 45th weeks of 2020 showed a moderate negative correlation in most census divisions, with mean correlation coefficients of -0.352 between SARS-CoV-2 and IVA, -0.327 between SARS-CoV-2 and IVB. The weekly percent positive of influenza virus cases in the United States showed a significant reduction between the 14th and 45th weeks of 2020 and the same weeks in 2016-2019, which partly verified the negative correlation between COVID-19 and influenza.Interpretation: As synchronous seasonality commonly exists among human coronaviruses and influenza viruses, seasonal adjustment is necessary before the pathogen-pathogen correlation analysis can be performed. The present study revealed a negative correlation between SARS-CoV-2 and influenza viruses, which was obscured by strong synchronous seasonality. According to our study, COVID-19 may unfortunately increase in winter due to its seasonal pattern, but a simultaneous outbreak of influenza and COVID-19 may not occur this winter due to the negative interaction between these two pathogens.Funding Statement: This study was funded by the Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20190808152613121) and the Shenzhen-Hong Kong Institute of Brain Science – Shenzhen Fundamental Research Institutions (2019SHIBS0003).Declaration of Interests: We declare no competing interests.

Comparison of acute pneumonia caused by SARS-COV-2 and other respiratory viruses in children: a retrospective multi-center cohort study during COVID-19 outbreak (preprint)

Background: Until July 14, 2020, coronavirus disease-2019 (COVID-19) has infected more than 130 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared to those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. Methods: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. Results: Compared to the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38) (all P ＜0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P =0.048), and lower cases with high fever (3/40 vs 167/284, P ＜0.001), requiring intensive care (1/40 vs 32/284, P ＜0.047) and with shorter symptomatic duration (median 5 vs 8 days, P ＜0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than in the viral pneumonia cohort (all P ＜0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared to duration in 39 children without antiviral therapy [median 10 vs. 9 days, P =0.885]. Conclusion: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonias. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.

Ceftazidime Is a Potential Drug to Inhibit SARS-CoV-2 Infection In Vitro by Blocking Spike Protein-ACE2 Interaction (preprint)

Coronavirus Disease 2019 (COVID-19) spreads globally as a sever pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cell entry of SARS-CoV-2 mainly depends on binding of the viral spike (S) proteins to angiotensin converting enzyme 2 (ACE2) on host cells. Therefore, repurposing of known drugs to inhibit S protein-ACE2 interaction could be a quick way to develop effective therapy for COVID-19. Using a high-throughput screening system to investigate the interaction between spike receptor binding domain (S-RBD) and ACE2 extracellular domain, we screened 3581 FDA-approved drugs and natural small molecules and identified ceftazidime as a potent compound to inhibit S-RBD-ACE2 interaction by binding to S-RBD. In addition to significantly inhibit S-RBD binding to HPAEpiC cells, ceftazidime efficiently prevented SARS-CoV-2 pseudovirus to infect ACE2-expressing 293T cells. The inhibitory concentration (IC50) was 113.2 M, which is far below the blood concentration (over 300 M) of ceftazidime in patients when clinically treated with recommended dose. Notably, ceftazidime is a drug clinically used for the treatment of pneumonia with minimal side effects compared with other antiviral drugs. Thus, ceftazidime has both anti-bacterial and anti-SARS-CoV-2 effects, which should be the first-line antibiotics used for the clinical treatment of COVID-19.

An Antioxidant Enzyme Therapeutic for COVID-19 (preprint)

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. We report herein a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.