ABSTRACT
School closures have been used as one of the main nonpharmaceutical interventions to overcome the spread of SARS-CoV-2. Different countries use this intervention with a wide range of time intervals from the date of the first confirmed case or death. This study aimed to investigate whether fast or late school closures affect the cumulative number of COVID-19 cases or deaths. A worldwide population-based observational study has been conducted and a range of attributes were weighted using 10 attribute weighting models against the normalized number of infected cases or death in the form of numeric, binominal and polynomial labels. Statistical analysis was performed for the most weighted and the most common attributes of all types of labels. By the end of March 2021, the school closure data of 198 countries with at least one COVID-19 case were available. The days before the first school closure were one of the most weighted factors in relation to the normalized number of infected cases and deaths in numeric, binomial, and quartile forms. The average of days before the first school closure in the lowest quartile to highest quartile of infected cases (Q1, Q2, Q3 and Q4) was -6.10 [95% CI, -26.5 to 14.2], 9.35 [95% CI, 2.16 to 16.53], 17.55 [95% CI, 5.95 to 29.15], and 16.00 [95% CI, 11.69 to 20.31], respectively. In addition, 188 countries reported at least one death from COVID-19. The average of the days before the first school closure in the lowest quartile of death to highest quartile (Q1, Q2, Q3 and Q4) was -49.4 [95% CI, -76.5 to -22.3], -10.34 [95% CI, -30.12 to 9.44], -18.74 [95% CI, -32.72 to -4.77], and -12.89 [95% CI, -27.84 to 2.06], respectively. Countries that closed schools faster, especially before the detection of any confirmed case or death, had fewer COVID-19 cases or deaths per million of the population on total days of involvement. It can be concluded that rapid prevention policies are the main determinants of the countries' success.
ABSTRACT
Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5' ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.