Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFß1, TGFß3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of FoxP3, STAT5+, IFNγ-R1, and ROR alpha+, were measured at day 1, day 7, day 14, day 21, and day 28 post-infection. Severe cases showed a significantly stronger increase than mild patients in levels of all cytokines (except IL-9) and all gene expression on day 1 of infection. Some cytokine levels dropped to levels comparable to mild cases at later time points. Further analysis identified IFNγ as a marker of severity throughout the disease course, while TGFß1, IL-6, and IL-17 were markers of severity only at an early phase. Importantly, this study revealed a striking low IL-9 level and high IFNγ/IL-9 ratio in the plasma of patients who later died compared to mild and severe cases who recovered, suggesting that this could be an important biomarker for predicting the severity of COVID-19 and post-COVID-19 syndrome.

Nasopharyngeal carriage and antibiotic susceptibility patterns of streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis and staphylococcus aureus among urban Ugandan children post-PCV10 introduction: a cross-sectional study.

In 2013, Uganda introduced the PCV10 pneumococcal vaccine and it is given to children at 6, 10 and 14 weeks after birth. Carriage prevalence studies post PCV10-introduction are necessary for monitoring the impact of vaccination and trends in antibiotic resistance. Here, we studied carriage/antibiotic resistance of Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus isolated from 194 children at the Mulago Assessment Centre clinic in Kampala-Uganda, 5 years post-PCV10 introduction. Almost all the children were vaccinated with PCV10 (98.5%, 191/194). The overall carriage prevalence (any species) was 62% (120/194), and it was associated with a history of antibiotics use (p=0.0159) and having respiratory symptoms (p=0.0003). The pneumococcus, H. influenzae, M. catarrhalis, and S. aureus carriage prevalence was 46% (90/194), 21% (40/194), 7% (14/194), and 6% (12/194), respectively. Species co-carriage occurred in 32 children (17%, 32/194), predominantly multidrug resistant pneumococcus + H. influenzae (23 children). Furthermore, pneumococci were highly resistant to cotrimoxazole (100%), erythromycin (76%), and tetracycline (52%), 42% being multidrug-resistant. Overall, we note an increase in antibiotic resistance post-PCV10 introduction, and microbial shifts i.e., a decrease in pneumococcus, M. catarrhalis and S. aureus carriage and an increase in H. influenzae carriage suggesting vaccine-associated perturbation of the respiratory ecology.