The process of adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans probably had started decades ago, when its ancestor diverged from the bat coronavirus. The adaptive process comprises strategies the virus uses to overcome the respiratory tract defense barriers and replicate and shed in the host cells. These strategies include the impairment of interferon production, hiding immunogenic motifs, avoiding viral RNA detection, manipulating cell autophagy, triggering host cell death, inducing lymphocyte exhaustion and depletion, and finally, mutation and escape from immunity. In addition, SARS-CoV-2 employs strategies to take advantage of host cell resources for its benefits, such as inhibiting the ubiquitin-proteasome system, hijacking mitochondria functions, and usage of enhancing antibodies. It may be anticipated that as the tradeoffs of adaptation progress, the virus destructive burden will gradually subside. Some evidence suggests that SARS-CoV-2 will become part of the human respiratory virome, as had occurred with other coronaviruses, and coevolve with its host.

Abstract Before eliciting an adaptive immune response, SARS-CoV-2 must overcome seven constitutive respiratory defense barriers. The first is the mucus covering the respiratory tract’s luminal surface, which entraps inhaled particles, including infectious agents, and eliminates them by mucociliary clearance. The second barrier comprises various components present in the airway lining fluid, the surfactants. Besides providing low surface tension that allows efficient gas exchange at the alveoli, surfactants inhibit the invasion of epithelial cells by respiratory viruses, enhance pathogen uptake by phagocytes, and regulate immune cells’ functions. The respiratory tract microbiota constitutes the third defense barrier against SARS-CoV-2. It activates the innate and adaptive immune cells and elicits anti-infectious molecules such as secretory IgA antibodies, defensins, and interferons. The fourth defense barrier comprises the antimicrobial peptides defensins, and lactoferrin. They show direct antiviral activity, inhibit viral fusion, and modulate the innate and adaptive immune responses. Secretory IgA antibodies, the fifth defense barrier, besides protecting the local microbiota against noxious agents, also inhibit SARS-CoV-2 cell invasion. If the virus overcomes this barrier, it reaches its target, the respiratory epithelial cells. However, these cells also act as a defense barrier, the sixth one, since they hinder the virus’ access to receptors and produce antiviral and immunomodulatory molecules such as interferons, lactoferrin, and defensins. Finally, the sensing of the virus by the cells of innate immunity, the last constitutive defense barrier, elicits a cascade of signals that activate adaptive immune cells and may inhibit the development of productive infection. The subject of the present essay is discussing these mechanisms.

Abstract In the absence of vaccines and effective antiviral drugs, control of the spread of coronavirus disease (Covid-19) relies mainly on the adequacy of public health resources and policies. Hence, failure to establish and implement scientifically reliable control measures may have a significant effect on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity of the disease, and death toll. The average number of secondary transmissions from an infected person, or reproduction numbers (R0 and R), and the points at which the collective immunity begins to reduce the transmission of the infection, or herd immunity thresholds, are important epidemiological tools used in strategies of Covid-19 control, suppression, and mitigation. However, SARS-CoV-2 transmission through asymptomatic carriers and, possibly, aerosols, has been ignored, and this may affect the effectiveness of Covid-19 control strategies. Therefore, consideration of the two possible ways of transmission would substantially increase the values of reproduction numbers, but if estimates of the contingent of the population naturally resistant to the virus, plus those with pre-existing cross-immunity to SARS-CoV-2 were considered, the evaluation of herd immunity thresholds should reach their real and achievable levels.