![]() įollowing an unprecedented effort of biomedical research and mobilization of resources, two mRNA vaccines – namely BNT162b2 (Comirnaty TM) from Pfizer-BioNTech and the mRNA-1273 of Moderna (encoded antigen: SARS-CoV-2 S protein of the Wuhan-Hu-1 strain) – were the first to receive FDA emergency use authorization. These immune responses are age- and gender-dependent and may either mount poorly in a background of genetic causes and pre-existing morbidities, or become very intense and essentially uncontrolled in severe disease leading to ARDS and systemic failure. As SARS-CoV-2 initially infects the upper RS, defensive immune responses start to develop at respiratory mucosal surfaces, and this is followed by systemic immunity. ![]() SARS-CoV-2 infection in healthy individuals triggers innate as well as adaptive immune system responses, that is, CD4 + and CD8 + T cells and antibodies, including neutralizing antibodies (NAbs) produced by terminally differentiated B cells, which altogether suppress the extent of infection. In a recent trial, in which young people were intentionally exposed to a low dose of SARS-CoV-2, nearly half of the participants did not become infected, some were asymptomatic, and those who developed COVID-19 reported mild to moderate symptoms, including sore throats, runny noses, sneezing, and loss of sense of smell and taste fever was less common, and no one developed a persistent cough. It has been postulated that higher pediatric innate interferon responses restrict viral replication and disease progression. The risk for severe COVID-19 increases significantly with age or pre-existing comorbidities, and younger individuals have a substantially lower risk – even compared to influenza infection – for developing severe COVID-19. A minority will require hospitalization this is due to severe symptoms which develop due to extensive inflammation, a process often referred to as a ‘cytokine storm’, causing ARDS which may be accompanied by viremia and can lead to systemic multiorgan collapse. ![]() In most of SARS-CoV-2-infected carriers the virus is contained in the upper RS, resulting in either no symptoms or mild symptoms. SARS-CoV-2 infection of human cells proceeds via its binding to the cell surface protein ACE2 through the RBD of its protruding S glycoprotein which remains in a metastable prefusion state through the association of subunits 1 (S1) and 2 (S2) via noncovalent interactions the infection process is also facilitated by host proteases. If systemic collapse and death are avoided, the postulated direct virus ‘attack’ – or indirect effects due to cytokine storm or imbalance of the renin–angiotensin system (RAS) – causing multiorgan damage, possibly foster systemic defects which cause a chronic condition (referred to as long COVID-19) which is independently associated with the severity of the initial illness. This may be due to the broad expression of its receptor angiotensin-converting enzyme 2 (ACE2) in several cell types and tissues which results in an expanding tropism of SARS-CoV-2 for various critical organs (heart, pancreas, kidneys, etc.). ARDS may then lead to organ damage beyond the RS because of micro-/macro-thromboembolism, hyperinflammation, aberrant complement activation, or extended viremia. In patients with severe disease, infection of airway and lung tissues may cause pneumonia and excessive inflammation which can lead to acute respiratory distress syndrome (ARDS) (see Glossary) ( Box 1). Although SARS-CoV-2 may also circulate in the gastrointestinal tract, being a respiratory virus, the virus itself or its related antigens will not, in most cases, impact tissues and organs other than the respiratory system (RS) ( Box 1). Nevertheless, for the majority of SARS-CoV-2-infected individuals, COVID-19 will remain asymptomatic or only mildly symptomatic. ![]() ) and has resulted in millions of deaths worldwide. Fighting the COVID-19 pandemic with SARS-CoV-2 S protein-encoding mRNA vaccinesĬOVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( Box 1 ![]()
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