Perspective of the Relationship between the Susceptibility to Initial SARS-CoV-2 Infectivity and Optimal Nasal Conditioning of Inhaled Air

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as with the influenza virus, has been shown to spread more rapidly during winter. Severe coronavirus disease 2019 (COVID-19), which can follow SARS-CoV-2 infection, disproportionately affects older persons and males as well as people living in temperate zone countries with a tropical ancestry. Recent evidence on the importance of adequately warming and humidifying (conditioning) inhaled air in the nasal cavity for reducing SARS-CoV-2 infectivity in the upper respiratory tract (URT) is discussed, with particular reference to: (i) the relevance of air-borne SARS-CoV-2 transmission, (ii) the nasal epithelium as the initial site of SARS-CoV-2 infection, (iii) the roles of type 1 and 3 interferons for preventing viral infection of URT epithelial cells, (iv) weaker innate immune responses to respiratory viral infections in URT epithelial cells at suboptimal temperature and humidity, and (v) early innate immune responses in the URT for limiting and eliminating SARS-CoV-2 infections. The available data are consistent with optimal nasal air conditioning reducing SARS-CoV-2 infectivity of the URT and, as a consequence, severe COVID-19. Further studies on SARS-CoV-2 infection rates and viral loads in the nasal cavity and nasopharynx in relation to inhaled air temperature, humidity, age, gender, and genetic background are needed in this context. Face masks used for reducing air-borne virus transmission can also promote better nasal air conditioning in cold weather. Masks can, thereby, minimise SARS-CoV-2 infectivity and are particularly relevant for protecting more vulnerable persons from severe COVID-19.

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

“…The nasal epithelium in the upper respiratory tract (URT) is the initial site of infection via inhaled SARS-CoV-2 virions [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Early and effective antigen non-specific, innate immune responses limit viral replication and help eliminate the virus in the URT [ 12 , 13 , 14 , 15 ]. Innate immune responses also orchestrate subsequent adaptive immune responses involving antibodies produced by plasma cells derived from bone-marrow-derived B lymphocytes (B cells) and effector thymus-processed lymphocytes (T cells) in local lymphoid tissue a few days after infection, which contribute to resolving the infection [ 14 , 15 , 16 ].…”

“…These processes are illustrated in Figure 1 . Healthy persons can eliminate SARS-CoV-2 with either no detectable symptoms or only mild COVID-19 symptoms (defined here as not requiring hospital treatment) as a result of rapid and effective innate and adaptive immune responses in the URT [ 12 , 13 , 14 , 15 , 16 ].…”

“…Protective innate immunity in the URT typically involves: (i) the barrier function of the mucus layer; (ii) the binding of virions by mucins as well as antibacterial proteins and peptides such as defensins and collectins in the mucus; (iii) complement activation by the alternative and lectin pathways through the recognition of altered surfaces in virions and infected cells to promote lysis, opsonization and inflammation; (iv) the induction of an anti-viral state in infected and neighboring epithelial cells through the inhibition of protein synthesis and mRNA degradation, and the activation of phagocytic cells and antigen-presenting dendritic cells. This entails pathogen-associated molecular patterns (PAMPs) being recognized by cellular pattern recognition receptors (PRRs) and the production of types 1 and 3 interferons (IFNs); (v) the activation of macrophages and dendritic cells, resulting in the production of cytokines such as IL-1, IL-6, IL-12, IL-18 and TNF that promote an inflammatory response locally and systemically, activate natural killer (NK) cells to lyse virus infected cells and promote adaptive immune responses; (vi) innate T cells recognizing damage-associated molecular patterns (DAMPs) in infected epithelial cells and secreting type 2 IFNγ, which further activates NK cells, phagocytes, dendritic cells and the adaptive immune response [ 15 ].…”

“…IgG and IgM antibodies in the nasal mucosa can also similarly neutralize virions and additionally activate complement through the classical pathway to lyse virions and infected epithelial cells. IgG antibodies can moreover promote Fc receptor-mediated phagocytosis of virions [ 15 ]. T H cells in URT lymphoid tissues activate B cells and promote immunoglobulin class switching and the affinity maturation of antibodies.…”

“…The importance of adequately warming and humidifying inhaled air in the nose (termed nasal air conditioning), a process that is influenced by age, air quality, gender and host genetics, for generating optimal innate and adaptive immune responses against SARS-CoV-2 in the URT was recently highlighted [ 14 , 15 ]. The significance of nasal air conditioning in resisting infection is further supported by evidence that the S protein of the Wuhan strain of SARS-CoV-2 promotes better infectivity at 33 °C than 37 °C [ 17 ].…”