Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

Abstract

Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations.
 Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher’s exact test was used for comparison of allele frequencies.
 Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alterative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world.
 Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.

Anti-spike S1 IgA, anti-spike trimeric IgG, and anti-spike RBD IgG response after BNT162b2 COVID-19 mRNA vaccination in healthcare workers

“…Moreover, vaccine efficacy for preventing COVID-19 symptomatic illness was significantly increased after the second dose (i.e., 57% to 94%), with a similar but more marginal effect on hospitalizations (i.e., 74% to 87%) [26] . Taken together, this data strongly suggests that the lower anti-SARS-CoV-2 neutralizing IgA antibodies response observed in our study after a single mRNA vaccine dose would actually mirror a still insufficient mucosal protection against SARS-CoV-2, thus corroborating current beliefs that the second mRNA vaccine dose is essential for achieving a sufficient level of herd immunity [27] , which may hence at least partially develop through an adequate increase of serum and mucosal levels of anti-SARS-CoV-2 IgA neutralizing antibodies. Another important aspect that has emerged from our study, is that the relative increase from baseline of anti-spike S1 IgA levels was inversely correlated with age, as it was the increase of anti-spike trimeric IgG, so that consideration shall be given to more strictly monitoring both antibodies classes in older people and eventually define a personalized vaccination program (i.e., using a third booster).…”

Role of biochemical markers in the monitoring of COVID-19 patients

“…Previous reports suggest that COVID-19 patients with different complications (inflammation, co-infection and thrombosis) can be categorized by analytical patterns, where personalized therapy could contribute to lower early mortality rates (OR 0.144; CI: 0.03-0.686; p = 0.015) in patients, thus supporting the idea that each situation requires a therapeutic focus adjusted to the type of altered pattern (79).…”

Comparison of five commercial anti-SARS-CoV-2 total antibodies and IgG immunoassays after vaccination with BNT162b2 mRNA

“…This finding has now been confirmed in a kaleidoscope of real-world studies [14] [15] [16] , and should hence be a guide for future vaccination programs. Over time, the monitoring of neutralizing anti-SARS-CoV-2 antibody response is paramount, as it has been previously reported that the inter-individual response to vaccination may vary widely (i.e., up to 30%) [17] , and that humoral anti-SARS-CoV-2 immunity tends to progressively fade over time [18] [19] , thus leading the way to the consideration for administration of additional vaccine boost(s) when the titer of neutralizing anti-SARS-CoV-2 antibodies would fall below a protective limit. Although anti-SARS-CoV-2 neutralizing antibodies titration before and after vaccination would be necessary for fully, though unpractically, optimizing vaccination programs [20] , clear evidence has been provided that commercial immunoassays used for this purpose reliably mirrors the humoral response, thus providing trustable data that could be used for deciding the most suitable vaccination plan on an individual basis.…”