Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

Evropi Amanatidou; Anna Gkiouliava; Eva Pella; Maria Serafidi; Dimitrios Tsilingiris; Natalia G Vallianou; Irene Karampela; Maria Dalamaga

doi:10.1016/j.metop.2022.100180

Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

Metabol Open. 2022 Mar 17:14:100180. doi: 10.1016/j.metop.2022.100180. eCollection 2022 Jun.

Authors

Evropi Amanatidou¹, Anna Gkiouliava¹, Eva Pella¹, Maria Serafidi¹, Dimitrios Tsilingiris², Natalia G Vallianou³, Irene Karampela⁴, Maria Dalamaga⁵

Affiliations

¹ Laboratory of Biomathematics, School of Medicine, University of Thessaly, Larissa, Greece.
² First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
³ First Department of Internal Medicine, Evangelismos General Hospital, Athens, Greece.
⁴ Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Chaidari, Athens, Greece.
⁵ Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, Greece.

Abstract

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions against the global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates of protection against severe disease and mortality. Barely a year after vaccines became available, the Omicron variant and its unprecedented speed of transmission has posed a new challenge. Overall, Omicron presents increased immune escape, transmissibility, and decreased pathogenicity. Vaccines do not offer a full protection against SARS-CoV-2 acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who may in turn spread the virus to others. Breakthrough infections may be causally related to the viral profile (viral variant and load, incubation period, transmissibility, pathogenicity, immune evasion), immunity characteristics (mucosal versus systemic immunity, duration of immunity, etc.), host determinants (age, comorbidities, immune status, immunosuppressive drugs) and vaccination properties (platform, antigen dose, dose number, dose interval, route of administration). Determining the rate of breakthrough infections may be challenging and necessitates the conduction of population-based studies regarding vaccine effectiveness as well as neutralizing antibody testing, a surrogate of immune protection. In this review, we analyze the causes of breakthrough infections, their clinical consequences (severity of infection and transmission), methods of determining their incidence as well as challenges and perspectives. Long COVID as well as multi-inflammatory syndrome in adolescents may be significantly reduced in breakthrough infections. The need for universal pancoranavirus vaccines that would aim at protecting against a plethora of SARS-CoV-2 variants as well as emerging variants is discussed. Finally, novel vaccine strategies, such as nasal vaccines, may confer robust mucosal and systemic protection, reducing efficiently transmission.

Keywords: Antibody; Breakthrough infection; COVID-19; Immunity; Neutralizing antibody; Omicron; Pancoronavirus; SARS-CoV-2; Vaccine; Variant; Variant of concern.