COVID-19 severity, miR-21 targets, and common human genetic variation. Letter regarding the article 'Circulating cardiovascular microRNAs in critically ill COVID-19 patients'

In a recent article by Garg et al.,1 serum levels of five microRNAs (miRs) were monitored in intensive care unit patients with severe COVID-19 pneumonia requiring invasive ventilation. The miR levels were compared to patients with severe influenza resulting in acute respiratory distress syndrome and healthy controls. For miR-21, a microRNA that is associated with cardiac fibroblast dysfunction,1 the authors observed elevated levels in acute COVID-19 patients and positive associations (P ≲ 0.05) with the number of intensive care unit days on ventilation or vasopressor, dialysis and extracorporeal membrane oxygenation. A negative association was observed with lactate dehydrogenase levels.

miR-21 is an abundant miR implicated in different regulatory pathways and exhibiting altered levels in circulation in neoplastic and other diseases; insight into its actions might lead to new strategies for therapeutic intervention.1, 2 Notably, coronaviruses have binding (target) sites for miR-21. SARS-CoV-2, or inflammatory or other affected processes, might thus alter circulating miR-21 levels.

An approximately 65 kb region of chromosome 3, in band 3p21.31, is the prime locus stably associated with COVID-19 severity.3 It spans a haplotype block, i.e. a segment of DNA that is typically inherited as a whole, showing almost no trace of recombination,

and often exhibits few block variants (haplotypes). The risk haplotype is most frequent (≈30%; Figure 1A) in South Asian populations and was apparently the major haplotype in Neanderthals.3 It covers a partly intronic segment of the LZTFL1 gene and DNA upstream of the gene SLC60A2. Some 20 single nucleotide polymorphism (SNP) variants distributed along the haplotype block show maximal effect3, 4 and almost identical minor allele frequencies (Figure 1A), thus constituting a checklist of candidate causal SNPs.