KINETICS OF ANTIBODIES AND CYTOKINE LEVELS IN COVID-19 PATIENTS AND THE ROLE OF AN UNDERLYING HIV INFECTION IN COVID-19 SEVERITY

Abstract

Background Upon exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), antibody responses are generated but their overtime kinetics remain unclear. A hyper-inflammatory state, defined by overproduction of cytokines, has been thought to be the main driver of pathogenesis. However, it has not been defined if these cytokines associate with severe disease outcome and how they vary over time. Certain underlying non-communicable diseases have been identified to play a role in enhancing Corona virus disease 2019 severity (COVID-19). Effect of an underlying human immunodeficiency virus infection (HIV) remains contradictory and warrants further understanding. Here, the study investigated the kinetics of SARS-CoV-2 antibodies and cytokine levels among infected patients with varying clinical presentations and compared HIV positive and negative COVID-19 patients. Methods 264 COVID-19 patients presenting in two Kenyan hospitals were longitudinally sampled across 5 time points where a total of 460 blood samples were collected. A commercial enzyme linked immunosorbent assay (ELISA) protocol was used to collectively measure anti-receptor binding domain (RBD) -IgG, IgM, and IgA antibodies and an in-house developed ELISA protocol to measure anti-spike IgG antibodies. Cytokine measurements were done in 22 patients utilizing Luminex assay. Both antibody and cytokine concentrations were then compared between mild and severely sick COVID-19 patients. Statistical tests of comparison were used to compare clinical data of HIV positive and negative COVID-19 patients. vi Results Both anti-spike IgG and anti-RBD (IgG, IgM, and IgA) antibodies increased significantly from day 0 to day 28 (P <0.0001) and were then maintained without significant decay for 6 months of the study (P=0.2003) and (P=0.9) respectively. The two antibody assays correlated positively (R=0.87, P value <0.001). Antibody titers were initially higher among severe than mildly sick patients with a significant difference observed at day 14 (P<0.05). However, the titers of mild patients caught up with those of severe patients at later time points. Spike IgG were positively associated with increase in time, disease severity and age. Inflammatory cytokines and chemokines, macrophage chemoattractant protein-1, monocyte inflammatory protein-1alpha and beta,Interleukin-18, Interleukin-8 and Eotaxin were significantly higher among the severe than mildly sick patients (P<0.05) in at least one time point and were maintained without significant reduction over a month (P>0.05). Clinical presentations, laboratory measurements and SARS-CoV-2 antibody responses were statistically similar between HIV positive and negative patients (P >0.05). Conclusion Majority of the patients’, both severely and mildly sick, sero-converted for both anti-RBD (IgG, IgM, and IgA) and anti-spike IgG antibodies which remained stable over 6 months. Higher inflammatory cytokines and chemokines among the severe than mildly sick patients suggested a heightened inflammation across the month after infection which could be playing an important role in pathogenesis. Underlying HIV infection did not significantly affect COVID-19 clinical presentation, laboratory measurements and SARS-CoV-2 antibody responses. vii Recommendations Further studies should determine SARS-CoV-2 antibody functionalities and their longevity beyond 6 months. Use of anti-inflammatories to counter the inflammatory cytokines are warranted. Compliance to anti-retroviral therapy is key as it could be playing a role in limiting COVID-19 severity