ABSTRACT
SARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown. We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period. Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24). These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021. This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.
Subject(s)
COVID-19ABSTRACT
The SARS-CoV-2 omicron BA.5 subvariant is progressively displacing earlier subvariants, BA.1 and BA.2, in many countries. One possible explanation is the ability of BA.5 to evade immune responses elicited by prior BA.1 and BA.2 infections. The impact of BA.1 infection on the risk of reinfection with BA.5 is a critical issue because adapted vaccines under current clinical development are based on BA.1. We used the national Portuguese COVID-19 registry to analyze the risk of BA.5 infection in individuals without a documented infection or previously infected during periods of distinct variants' predominance (Wuhan-Hu-1, alpha, delta, BA.1/BA.2). National predominance periods were established according to the national SARS-CoV-2 genetic surveillance data (when one variant represented >90% of the sample isolates). We found that prior SARS-CoV-2 infection reduced the risk for BA.5 infection. The protection effectiveness, related to the uninfected group, for a first infection with Wuhan-Hu-1 was 52.9% (95% CI, 51.9 - 53.9%), for Alpha 54.9% (51.2 - 58.3%), for Delta 62.3% (61.4 - 63.3%), and for BA.1/BA.2 80.0% (79.7 - 80.2%). The results ought to be interpreted in the context of breakthrough infections within a population with a very high vaccine coverage (>98% of the study population completed the primary vaccination series). In conclusion, infection with BA.1/BA.2 reduces the risk for breakthrough infections with BA.5 in a highly vaccinated population. This finding is critical to appraise the current epidemiological situation and the development of adapted vaccines.
Subject(s)
Breakthrough Pain , COVID-19ABSTRACT
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) show specific epigenetic and gene expression signatures of the disease. However, it is unknown whether these signatures in ME/CFS include abnormal levels of the human angiotensin-converting enzyme ACE and ACE2, the latter being the main receptor described for host-cell invasion by SARS-CoV-2. To investigate that, we first reviewed published case-control genome-wide association studies based on single nucleotide polymorphism data, case-control epigenome-wide association studies based on DNA methylation data, and case-control gene expression studies based on microarray data. From these published studies, we did not find any evidence for a difference between patients with ME/CFS and healthy controls in terms of genetic variation, DNA methylation, and gene expression levels of ACE and ACE2. In line with this evidence, the analysis of a new data set on the ACE/ACE2 gene expression in peripheral blood mononuclear cells did not find any differences between a female cohort of 37 patients and 34 age-matched healthy controls. Future studies should be conducted to extend this investigation to other potential receptors used by SARS-CoV-2. These studies will help researchers and clinicians to better assess the health risk imposed by this virus when infecting patients with this debilitating disease.