Sex-based clinical and immunological differences in COVID-19

BackgroundMales and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take sex as consideration. MethodsWe performed an unbiased sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and SARS-CoV-2 specific antibody levels of 1,558 males and 1,499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. Total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)-specific IgM and IgG levels were measured by chemiluminescence. ResultsWe found that the mortality and ICU admission rates were approximately 2-fold higher in males than that in females (P<0.005). Survival analysis revealed that sex is an independent prognostic factor for COVID-19 (Hazard ratio=2.2, P=0.003). The concentration of inflammatory factors in peripheral blood was significantly higher in males. Besides, the renal and hepatic abnormality induced by COVID-19 was more common in males during the hospitalization. The analysis of lymphocyte subsets revealed that the percentage of CD19+ B cell and CD4+ T cell was significantly higher in females (P<0.001) during hospitalization, indicating the stronger humoral immunity in females than males. Notably, the protective IgG sharply increased and reached a peak in the fourth week after symptom onset in females, while gradually increased and reached a peak in the seventh week in males. ConclusionsThe unfavorable prognosis of male COVID-19 patients may result from the weak humoral immunity and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients. Hormonal or convalescent plasma therapy may help improve the immunity of males to fight against SARS-CoV-2 infection.

Laboratory Testing Implications of Risk-Stratification and Management for Improving Clinical Outcomes of COVID-19 Patients

The high mortality rate of COVID-19 patients is mainly caused by the progression from mild to critical illness. To identify the key laboratory indicators and stratify high-risk COVID-19 patients with progression to severe/critical illness, we compared 474 moderate patients and 74 severe/critical patients. The laboratory indicators, including lactate dehydrogenase (LDH), monocytes percentage, etc. were significantly higher in the severe/critical patients (P <0.001) and showed a noticeable change at about a week before the diagnosis. Based on these indicators, we constructed a risk-stratification model, which can accurately grade the severity of patients with COVID-19 (accuracy = 0.96, 95% CI: 0.94 - 0.989, sensitivity = 0.98, specificity = 0.84). Also, compared with non-COVID-19 viral pneumonia, we found that COVID-19 had weaker dysfunction to the heart, liver, and kidney. The prognostic model based on laboratory indicators could help to diagnose, monitor, and predict severity at an early stage to those patients with COVID-19.

The Dynamic Changes of Antibodies against SARS-CoV-2 during the Infection and Recovery of COVID-19

Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P<0.01). The decrease of these IgG levels indicates the poor outcome of severe/critical patients. The RBD- and S-specific IgG levels are 2-fold higher in virus-free patients (P<0.05). Notably, we found that the patients who got re-infected had a low level of protective antibody on discharge. Therefore, our evidence proves that the dynamic changes of antibodies could provide an important reference for diagnosis, monitoring, and treatment, and shed new light on the precise management of COVID-19.