Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), characterized by pneumonia, lymphopenia, exhausted lymphocytes, and cytokine storms. While antibody production is significant, its protective or pathogenic role remains unclear. Understanding immunopathological changes in COVID-19 patients is crucial for drug discovery and clinical management. SARS-CoV-2 activates innate and adaptive immune responses, but uncontrolled inflammation and impaired adaptive immunity can lead to tissue damage. Severe cases show lymphopenia, reduced T and B cells, and increased neutrophils, indicating disease severity. Exhaustion markers on cytotoxic lymphocytes are upregulated in severe cases, but normalize in recovered patients. Convalescent plasma with neutralizing antibodies has shown clinical improvement in some severe cases. However, increased IgG responses in severe cases may indicate antibody-dependent enhancement (ADE), which could worsen outcomes. High levels of pro-inflammatory cytokines like IL-6 and IL-1β are associated with cytokine storms, leading to shock, organ failure, and pulmonary damage. Tocilizumab, an IL-6 receptor inhibitor, showed promise in treating severe cases. Mesenchymal stem cells (MSCs) may alleviate immunopathology due to their anti-inflammatory and reparative effects. Prognostic biomarkers for high-risk patients are needed, with age and comorbidities like hypertension and diabetes being risk factors. Standardized treatment protocols combining anti-inflammatory and antiviral drugs are essential. Traditional Chinese medicine has shown efficacy in vitro. Stress-induced neuroendocrine-immune crosstalk may also impact outcomes. Further research is needed to confirm the role of ADE and to develop effective therapies.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), characterized by pneumonia, lymphopenia, exhausted lymphocytes, and cytokine storms. While antibody production is significant, its protective or pathogenic role remains unclear. Understanding immunopathological changes in COVID-19 patients is crucial for drug discovery and clinical management. SARS-CoV-2 activates innate and adaptive immune responses, but uncontrolled inflammation and impaired adaptive immunity can lead to tissue damage. Severe cases show lymphopenia, reduced T and B cells, and increased neutrophils, indicating disease severity. Exhaustion markers on cytotoxic lymphocytes are upregulated in severe cases, but normalize in recovered patients. Convalescent plasma with neutralizing antibodies has shown clinical improvement in some severe cases. However, increased IgG responses in severe cases may indicate antibody-dependent enhancement (ADE), which could worsen outcomes. High levels of pro-inflammatory cytokines like IL-6 and IL-1β are associated with cytokine storms, leading to shock, organ failure, and pulmonary damage. Tocilizumab, an IL-6 receptor inhibitor, showed promise in treating severe cases. Mesenchymal stem cells (MSCs) may alleviate immunopathology due to their anti-inflammatory and reparative effects. Prognostic biomarkers for high-risk patients are needed, with age and comorbidities like hypertension and diabetes being risk factors. Standardized treatment protocols combining anti-inflammatory and antiviral drugs are essential. Traditional Chinese medicine has shown efficacy in vitro. Stress-induced neuroendocrine-immune crosstalk may also impact outcomes. Further research is needed to confirm the role of ADE and to develop effective therapies.