Omicron - The new SARS-CoV-2 challenge?

SARS-CoV-2 virus has infected nearly 300 M people worldwide and has been associated with over 6 M deaths by March 2022. Since the virus emergence in December 2019 in Wuhan, several new mutations have been described. The World Health Organization has developed a working name for these emerging variants according to their impact on the worldwide population. In this context a high alert has been paid to variants of concern (VOC) due to their high infectiousness and transmissibility patterns. The most recent VOC, Omicron (B.1.1.529), has become dominant in the shortest time ever and has placed Europe under an overwhelming and unprecedented number of new cases. This variant has numerous mutations in regions that are associated with higher transmissibility, stronger viral binding, affinity and antibody escape. Moreover, the mutations and deletions present in the spike protein suggest that the SARS-CoV-2 specific attachment inhibitors may not be the best option for Omicron therapy. Omicron is the dominant variant circulating worldwide and, at the end of February 2022, it was responsible for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, where the most common are BA.1 and BA.2 (or Nextstrain clade 21K and 21L, respectively). At a global level, it is possible to say that the proportion of BA.2 has been increasing relative to BA.1 and in some countries it has been replacing it at high rates. In order to better assess the Omicron effectiveness on antibody escape, spread and infectious ability it is of the highest relevance to maintain a worldwide tight surveillance. Even though this variant has been associated with a lower death rate, it is important to highlight that the number of people becoming infected is concerning and that further unpredictable mutations may emerge as the number of infected people rises.

Humoral response to pfizer BNT162b2 in peritoneal and hemodialysis patients: A comparative study

Background: Generalized immunization against COVID19 has become the cornerstone in prevention of Sars-CoV-2. Maintenance dialysis patients (MDP) are at higher risk of both exposure and mortality. Efficacy and security of Pfizer BNT 162b2 vaccine is well documented for the general population, but not in MDP, particularly in peritoneal dialysis (PD) patients. This study aims to compare humoral response between HD and PD patients. Methods: Observational prospective study including MDP on HD or PD program from a Portuguese middle-sized Nephrology Center, who received Pfizer-BNT162b2. Specific anti-Spike IgG was measured as arbitrary units per milliliter (AU/mL) on two separate occasions, corresponding to the first and second doses' humoral response. The two groups were compared both for absolute value and number of non-responders (NR) after both inoculations. Demographic data was also obtained and compared. Results: Of 73 patients enrolled, 67 were eligible for the final study: 42 HD and 25 PD patients. PD group developed significantly higher antibody titers both after first (Med 5.44 vs 0.99;p<0.01) and second dose (Med 170.43 vs 65.81;p<0.01). HD status was associated with non-responding after the first dose (Phi=0.383;p<0.01), but not after the second one (p=0.08). Age, Charlson Comorbidity Index and dialysis vintage were lower in the PD group (p<0.01;p=0.02;p<0.01, respectively). Conclusions: This study demonstrated a better humoral response to immunization with Pfizer BNT162b2 in PD patients, when comparing to HD patients, after both inoculations. Both groups showed substantial humoral response after just one dose of the vaccine. Older age and higher comorbidity burden may explain the relative immunogenicity deficit.

Predicting factors of humoral response to pfizer BNT 162B2 in hemodialysis patients

Background: Immunization against COVID19 has become the cornerstone in prevention of Sars-CoV-2. Maintenance Hemodialysis (HD) patients are at higher risk of both exposure and mortality. This study aims to describe humoral immunogenicity and suggest risk factors for low or absent response to Pfizer BNT162b2 in an HD cohort. Methods: Observational prospective study including a group of HD patients followed in a Portuguese Nephrology Center who received BNT162b2. Anti-Spike IgG measured as arbitrary units per milliliter (AU/mL) was obtained on two separate occasions, corresponding to the first and second doses' humoral response. Absolute IgG value, rate of Non-Responders (NR), IgG<1AU/mL after each dose, and Weak-Responders (WR), under Percentile 25 after each dose, were evaluated for risk factors that included demographic and analytical variables. Results: IgG anti-Spike levels showed a strong correlation with CCI and PTH after each inoculation (ρ=-0.64;-0.66/ ρ=0.56/0.65, respectively;p<0.01). Higher CCI and lower PTH was observed in NR subgroup after the 1st (p<0.01), whereas with the 2nd there was a lower albumin and PTH (p=0.01) and an association with female sex (p<0.01). Similarly, WR also showed higher CCI and lower PTH after the 1st (p=0.02) and 2nd doses (p<0.01), adding older age (p=0.03) and lower albumin (p=0.05) to the 2nd. After both inoculations, WR subgroup was associated with age over 75 yo (p=0.03);female sex (p=0.01), CCI over 8 (p=0.01), CVC over AVF/AVG (p<0.01), dialysis vintage under 24 mo (p=0.01) and PTH under 150 μg/L (p<0.01). A model combining CCI, sex (male) and vascular access (CVC) as a regression model associated those factors to WR after the 2nd dose with OR (95% CI): 1.81 (1.06-3.08);0.05 (0.01-0.65);13.55 (1.06-174.18), respectively (p=0.01). Conclusions: Older age, high CCI, low PTH and albumin, CVC over AVF/AVG and recently started dialysis (less than 2 years) relate to lower response. High comorbidity burden is suggested as a more significant risk factor than age alone. THe role of PTH as a marker of low immunogenicity in the HD population should be target of further investigation. Signalization of HD patients at risk of low response may play a key role in policy making, namely the necessity for booster doses, follow-up measurements and isolation methods.