**1. Introduction**

In December 2019, the apparent emergence of a new disease, the Coronavirus Disease 2019 (COVID-19), in Wuhan, Hubei, China, caused by a new coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), occurred [1–4]. This viral emerging zoonotic disease was initially linked to a fresh seafood market in Wuhan city, with the secondary human-to-human transmission, initially considered by droplets and later confirmed in an aerosolized way, among other potential and alternate routes of transmission [5–11], even including transmission from humanto-animals, particularly to dogs, different felines (cats, lions, and tigers) and minks, among others [12, 13]. Initially affecting China [14–16], the SARS-CoV-2 spread rapidly in a few days to other countries in Asia, as well as later to Europe [17–20], North America [21–23], Africa, and Latin America [9, 24–27]. On January 30, 2020, after the assessments of the Emergency Committee, under the International Health Regulations (IHR), the World Health Organization (WHO) Director General declared that the SARS-CoV-2 outbreak constitutes a Public Health Emergency of International Concern (PHEIC). On March 11, 2020, the WHO declared the SARS-CoV-2 outbreak as a pandemic. Two years later, the pandemic continues, summarizing a total of 628,184,448 cases up to October 25, 2022, with 6,580,107 deaths (**Figure 1**).

Over this time, the initial impact of the outbreak lead globally to generalized lockdowns and quarantine [28–30], a collapse of the health systems, especially in low- and middle-income countries [31], as well as devastating impacts on travel, tourism, economy, education, and multiple other societal sectors [32, 33]. Fortunately, only a low proportion of infected individuals develop mild or severe diseases that required hospitalization and admittance to an intensive care unit, but still, given the magnitude of the pandemic, imply a collapse in countries with limited resources and facilities. During 2020, no effective treatments and vaccines were available, only non-pharmacological interventions (NPI), including the massive use of face masks (including personal protection equipments [PPE], such as N95 filters, especially for healthcare workers), and after December 2021, some treatments, including the use dexamethasone [34–38], and RNA and viral vector vaccines, such as BNT162b2 vaccine (Pfizer/BioNTech®), the ChAdOx1 nCoV-19 vaccine (AstraZeneca/Oxford®), mRNA-1273 (Moderna®), among others, were available and widely used [39–45].

One of the major issues after 2021 was the emergence of the mutations of the SARS-CoV-2 leading to variants of different nature, particularly the variants of

#### **Figure 1.**

*COVID-19 dashboard showing the cumulated incidence, mortality, and vaccination, as well as their total during the last 28 days, evolution since 2020, and the top of countries in such indicators; up to October 25, 2022. (https:// gisanddata.maps.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6).*

#### **Figure 2.**

*SARS-CoV-2 variants and genomes were sequenced and collected at the GISAID database up to October 25, 2022. (https://www.gisaid.org/).*

interest (VOI), and the variants of concern (VOC), which decrease the protection capacity of used vaccines [40, 44, 46, 47]. The emergence of the VOCs, Alpha, Beta, Gamma, Delta, and Omicron (**Figure 2**), as well as the Omicron's sublineage during those months, have been a real challenge for prevention and control of the pandemic.
