COVID-19 inflammatory signature in a Mozambican cohort: unchanged red blood series and reduced levels of IL-6 and other proinflammatory cytokines

Abstract

Background: Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2.

Methods: A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories. Haematological, biochemical and cytokines measurement were performed on samples from the study participants. Principal component analysis (PCA) was performed to identify similar patterns among the study cases. Comparisons between groups were performed using the Kruskal-Wallis test. Receiver operating characteristic (ROC) and area under the curve (AUC) analysis were conducted to evaluate the ability of these parameters to distinguish severe from non-severe cases of SARS-CoV-2 infection.

Results: SARS-CoV-2 infection was associated with a significant (p < 0.05) decrease in peripheral blood absolute counts of total lymphocytes and eosinophils, below the reference values along with no abnormal change (p > 0.05) in red blood cell count, haemoglobin, platelets and other red series parameters. At the serum level, SARS-CoV-2 infection was associated with an increase in serum levels of C-reactive protein (C-RP) and glucose above the reference values and to a significant reduction a significant (p < 0.05) reduction in levels of interferon-gamma (INF-γ), Tumour Necrosis Factor alfa (TNF-α) and the interleukin 1 beta (IL-1β) and IL-6 in severe cases, when compared to negative cases. Haematological, biochemical and cytokine profiles segregate severe from non-severe cases of COVID-19 with an excellent performance of C-RP (AUC = 0.95; p < 0.001) and good performance of lymphocytes (AUC = 0.88; p < 0.001) and IL-15 (AUC = 0.86; p < 0.001).

Conclusion: The lack of variation in red and platelet series, coupled with a decrease in the levels of classical pro-inflammatory in severe cases, deviates from what has been reported in other contexts suggesting, that there may be peculiarities in COVID-19 manifestation within the context of this study population. Furthermore, these results identify parameters with potential for clinical management of COVID-19 and therefore good resource allocation, particularly for severe cases.

Keywords: Biochemistry; COVID-19; Cytokines; Haematology; Immunological signature; SARS-CoV-2.

Fig. 1

Associations of clinical state stratified into negative (n = 22), asymptomatic (n = 21), mild (n = 16), and severe (n = 21) cases with hematological parameters (A) White blood cells (WBC); (B) Lymphocytes (LYMP); (C) Eosinophils (EOS); (D) Neutrophils (NEUT); (E) Lymphocyte-to-Monocyte Ratio (LMR); (F) Neutrophil-to-Lymphocyte Ratio (NLR) and (G) Platelet-to-Lymphocyte Ratio (PLR) determined using the Kruskal‒Wallis test and adjusted by Dunn test with α = 0.05 Dashed line indicates parameter Mozambican reference value

Fig. 2

Association of clinical state stratified in negative, asymptomatic, mild, and severe groups, with hematological parameter (A) Red blood cells (RBC), (B) Haemoglobin (HGB), (C) Mean Corpuscular volume (MCV), (D) Platelet (PLT), (E) Red blood cell distribution width standard deviation (RDW-SD), (F) Red blood cell distribution width coefficient of variation RDW-CV, using Kruskal-Wallis Test and adjusted by Dunn Test with α = 0.05. Dashed line indicates parameter Mozambican reference value

Fig. 3

Association of clinical state stratified in negative (n = 22), asymptomatic (n = 21), mild (n = 16), and severe (n = 21) cases with biochemical parameter (A) Glucose, (GLUC); (B) Triglycerides, (TRIG); (C) Alanine transaminase, (AST); (D) Aspartate transaminase, (ALT); (E) Albumin, (ALB); (F) Urea, (URE); (G) C-reactive protein, (C-RP) using Kruskal‒Wallis Test and adjusted by Dunn Test with α = 0.05. Dashed line indicates parameter Mozambican reference value

Fig. 4

Association of clinical state stratified in negative (n = 22), asymptomatic (n = 21), mild (n = 16), and severe (n = 21) cases with cytokine (A) Interleukin-1 beta (IL-1β); (B) Interleukin-6, (IL-6); (C) Interferon Gama (IFN-γ); (D) Interleukin-15, (IL-15); (E) Interleukin-18, (IL-18) and (F) Transforming growth factor beta, (TGF-β) using Kruskal‒Wallis Test and adjusted by Dunn Test with α = 0.05

Fig. 5

SARS-CoV-2 severity associated parameters from hematology, biochemistry and cytokines looking at (A) Principal Component (PC) analysis of grouped parameters stratified by clinical states negative (n = 22), asymptomatic (n = 21), mild (n = 16), and severe (n = 21) indicated by color; (B) Correlation matrix of clinical state (as a continuous variable not including negative cases), age (in years), CT value and PC scores from previously analysis using Spearman Rank with α = 0.05. Results are shown as r values, with the strength of correlation as follows: 0-0.19 (very weak), 0.2–0.39 (weak), 0.40–0.59 (moderate), 0.6–0.79 (strong) and 0.8-1 (very strong); (C) Receiver Operator Curves (ROC) of severity associated parameters classifying non-severe (n = 42) from severe (n = 21) cases. The results are shown as Area Under the Curve (AUC) with the interpretation as follows: 0.5–0.6 (failed), 0.6–0.7 (worthless), 0.7–0.8 (poor), 0.8–0.9 (good), > 0.9 (excellent), with a α = 0.05

Fig. 6

Moderate and strong correlation plots using positive rt-PCR SARS-CoV-2 of C-RP with (A) Glucose, (GLUC); (B) Alanine transaminase, (AST); (C) Albumin, (ALB); (D) Neutrophils, (NEUT); (E) White Blood Cells, (WBC); (F) Eosinophils, (EOS); (G) Lymphocyte, (LYMP); (H) Neutrophils to Lymphocyte Ratio, (NLR); (I) Platelets to Lymphocyte Ratio, (PLR) and (J) Interleukin-15 (IL-15) using Spearman rank with a α = 0.05. Results are shown as r values, with the strength of correlation as follows: 0-0.19 (very weak), 0.2–0.39 (weak), 0.40–0.59 (moderate), 0.6–0.79 (strong) and 0.8-1 (very strong)