Since the description of the first cases in Wuhan, China, and until September 2023, more than 676 million cases of COVID-19 and nearly 7 million deaths have been reported worldwide [1]. Most of these deaths have occurred in the era before COVID-19 vaccines became available. The first descriptions reported that older adults or people with diabetes, hypertension and cardiovascular disease, obesity, lung disease, malignant neoplasms, and other diseases that cause immunocompromised, had a higher risk of more severe disease and higher mortality due to COVID-19 [2-4]. However, previously healthy people also experienced serious illness and death.

After unprecedented research, vaccination against SARS-CoV-2 began in December 2020 and with this strategy, the course of the pandemic would be modified. BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) were the main vaccines that demonstrated a reduction in hospitalization and death from SARS-CoV-2 in clinical trials [5-7]. Subsequently, new variants of SARS-CoV-2 emerged and variations in the effectiveness of the vaccines were reported [8]. However, mortality did not return to pre-vaccination levels.

A study in the United Kingdom that assessed the risk of severe COVID-19 after full vaccination of primary schedule and initial boosters, showed that older adults, those with comorbidities (≥ 5 comorbidities vs none), being male, and those with certain underlying health conditions (in particular, individuals receiving immunosuppressants) and those with chronic kidney disease remained at high risk [9].

Individuals with a history of COVID-19 infection were at reduced risk (infected ≥ 9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]).

Post-vaccination infection by COVID-19 is called breakthrough infection.

Breakthrough infections have been monitored around the world, mainly by measuring two parameters through immunological assays. The first, is the detection of IgG antibodies directed against the receptor-binding domain (RBD) of the S protein of SARS-CoV-2 (anti-S IgG) and the detection of neutralizing antibodies that block the interaction between the Angiotensin-converting enzyme II and the RBD of the S protein of SARS-CoV-2.

For example, in the follow-up of patients with the application of the BBV152 vaccine (COVAXIN) at a dose of 6 µg with Algel-MDG ensures the presence of neutralizing antibodies for up to 6 months after the second dose in 75% of the patients. However, after a third dose, the amount of serum-neutralizing antibodies increases with an increase of 48.5 times for the SARS-CoV-2 D614G variant and 410 times more for the Delta variant, taking into account that in studies such as this one by Mohan- Vadrevu et al. comorbidities are not taken into account and the real effectiveness demonstrated by studying the active infection of vaccinated individuals [10].

The monitoring of Breakthrough infections is essential to know the real effectiveness of the vaccines. Duarte et al. tracked confirmed COVID-19 cases after 14 days of vaccination with CoronaVac, finding 50 cases out of 2,263 vaccinated volunteers who had received two doses of vaccine. The final 9 volunteers were considered to have relevant diseases and symptoms, and as their main comorbidity, they were overweight; only two volunteers suffered an illness that required hospitalization. The authors propose that alterations such as overweight may interfere with the development of a powerful humoral immune response against the virus [11]. We mention that this study was carried out in the Latin population, as was one of our previous works where we showed that the majority of vaccinated patients who suffered Breakthrough infections had high blood pressure as a comorbidity in a percentage of 48.9% compared to 27.8% of the unvaccinated; As well as type 2 diabetes in 40.9% of those vaccinated, versus 27.1% of those not vaccinated [12]. Being overweight, high blood pressure, and type 2 diabetes, are three comorbidities that are very common in the Latin population and governments are making efforts to combat them.

As part of the follow-up for the at-risk population, prospective observational cohort studies have provided relevant data to increase knowledge of the disease in this population. The follow-up to Ben-Fredj et al. in Tunisia shows that breakthroung infection is more frequent in health workers, and smokers, and critical illness was more frequent in patients with advanced age, and cardiovascular disease [13].

In the largest cohort analyzed by Desantis et al. with a follow-up of 22,575 post-vaccinated individuals, other comorbidities of interest are added, such as asthma, and the immunocompromised patient, although without specifying the disease suffered, so we immediately analyze one of the most important immunocompromised states [14].

Breakthrough infection in patients with HIV was observed in 113,994 patients, who had mostly received doses of BNT162 51%, mRNA-1273 42%, and 7% received Ad26.COV2.S. There were 47 infections per 1,000 individuals during the COVID-19 waves following the start of vaccination. The cumulative incidence of infection after 275 days of complete vaccination was 3.8% (95% CI, 3.7%-3.9%). CD4+ count greater than 500 was associated with a lower risk of infection in the vaccinated population [15].

Following vaccination efforts around the world, the incidence of severe COVID-19 infection has decreased, declaring the end of the pandemic by the World Health Organization. However, efforts to keep vaccination active, especially in at-risk populations, must continue. In Mexico, vaccination programs include precisely this type of population and vaccination is currently being actively carried out. We must continue with active surveillance of breakthrough infections to identify comorbidities and improve patient prognosis.

All authors contributed equally to the conceptualization and writing work.