The impact of public responses toward healthcare workers on their work engagement and well-being during the Covid-19 pandemic.

Introduction/context: Healthcare workers (HCWs) play an important role in fighting against the COVID-19 pandemic. However, they have been exposed to mixed public responses more significantly during the COVID-19 pandemic, which have potentially affected their work and life. Aim: We aim to study what public responses toward HCWs existed, how and why such public responses impacted HCW's work engagement and well-being, and how Human Resource (HR) professionals navigate these impacts. These understandings are important for improving HCWs' work and life quality. Methods: We adopted a mixed approach including both quantitative and qualitative methods to investigate how the public responses impact HCWs' work engagement and well-being and how human resource management (HRM) shall intervene. Our quantitative study enables us to collect and analyze a large amount of public responses toward HCWs from the social media platform during the COVID-19 pandemic globally, and uncover the sentiments and topics of these pubic responses via big data and AI technologies. Our qualitative study allows us to understand how and why these public responses impact HCWs' work engagement and well-being via interviews and further identify how HR professionals shall navigate these impacts. Results: The sentiment analysis showed that 55.9% of the discussions toward HCWs were positive, 27.2% were neutral, and 16.9% were negative. The topic modeling analysis indicated that the commonly identified topics were related to fear (the negative responses) and gratitude (the positive responses). The interviews with 18 HCWs revealed that HCWs' work engagement and well-being were decreased by negative public responses through experiencing tension or disappointment due to social and physical ostracism, rejection, discrimination, and criticism. On the other hand, positive public responses in terms of encouragement, recognition, and tangible donations increased their work engagement and well-being. The analysis also suggested that occupational calling served as a mechanism that explained why public responses had such impacts on HCWs. The interview results also highlighted the significance of HRM in bridging positive public responses toward HCWs and revealed problems with communication from HRM during the pandemic. This research provides practical implications about how to improve HCWs work engagement and well-being during the pandemic via public and HRM efforts.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.