Table 1.

Risk and protecting factors and their correlations with the infection and severity of COVID-19 in adults

Risk factors for COVID-19 infection	Correlations
Older age	• Weaker immune defense against infectious pathogens [19] • Associated with more comorbidities [19] • Aging-related chronic pro-inflammatory status of the immune system with persistent low-grade innate immune activation [8]
Male sex	• Weaker immunity due to genetic and hormonal factors [8] • Normal serum testosterone level may foster viral entry into host cells and facilitate systemic dissemination of SARS-CoV-2 [20, 21] • Lifestyle that predisposes to infection (such as smoking) [8] • Higher levels of ACE2 on the endothelium of the pulmonary vessels [19]
Pre-existing comorbidities	• Weaker immune defense [19] • Pro-inflammatory status of the immune system [19]
Racial/ethnic disparities	• Difference in the essential workforce services, poverty, access to healthcare, and insurance [22] • Increase the potential exposure to SARS-CoV-2 and community transmission and delay the time from symptom onset to hospitalization [22] • Inequality in healthcare utilization [22]
Healthcare workers (HCWs)	• Higher exposed viral load • Increased viral exposure time
Protective factors for COVID-19 infection	Correlations
Diet and nutrition	• Cathelicidins and defensins result from the consumption of vitamin D can reduce viral replication rates and the levels of pro-inflammatory cytokines (e.g., IL-1, IL-6, IL-8, IL-12, and TNF-α) [23, 24] • Adequate vitamin D level may help to protect the respiratory epithelium from pathogenic invasion [12] • Vitamin C can help reduce levels of pro-inflammatory cytokines (e.g., TNF-α and IL-10) [25]
Vaccines	• More efficient production of neutralizing antibodies against SARS-CoV-2 at the beginning of the infection due to the larger number of activated B cells [26] • More effectively trained and sustained innate immunity [13]
Atopic conditions	• Lower expression of ACE2 receptor caused by type 2 inflammation [27] • Lower IFN-α production [26, 28] • Protective role of eosinophils in the airway [26, 28]
Risk factors for the severity and mortality of COVID-19 disease progression	Correlations
Older age	• High prevalence of comorbidities [8] • Decreased reserve capacity of vital organs [19] • Weaker immune defense [8] • Higher SARS-CoV-2 viral load [8] • Persistent low-grade innate immune activation [19] • Higher levels of pro-inflammatory cytokines [8]
Male sex	• Lower testosterone levels in aged and comorbid men may lead to male hypogonadism and induces cardiovascular events, exaggerating immune system, and coagulative response [20] • Higher frequency of underlying diseases such as type II diabetes and cardiovascular diseases [29] • Lower antibody production and delayed viral RNA clearance [29] • Higher risk of cytokine storm [29]
Pre-existing comorbidities	• Sustained low level of immunity status reduces the resistance to virus infection [8, 30] • Previous organ damage promotes the progression of COVID-19 [11]
Laboratory indices	• Significantly elevated inflammatory markers suggest a hyperinflammatory state in patients with severe disease [31] • May indicate the association with co-infection [31]
Pro-inflammatory cytokines	• Significantly higher levels of circulating IL-6, IL-8, IL-10, IL-2R, and TNF-α in severe cases [32] • Cytokine storm can develop a rapid inflammatory signaling cascade and lead to fatality in severe cases [33] • Deficiency in IFN-I response [8]
Complications	• Hypoxemia, acute respiratory distress syndrome (ARDS), metabolic acidosis, coagulopathy, and septic shock may cause loss of normal organ function (include hepatic, cardiovascular, and pulmonary function) [34–36]
Protective factors for the severity and mortality of COVID-19 disease progression	Correlations
Vaccine	• Induction of neutralizing antibodies [13] • Establishment of immune memory, including T-cell activation [13]