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Our understanding of risk factors and interventions influencing outcomes from COVID-19 has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of IFN homeostasis in the defense against SARS-CoV-2. As COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.