Humoral immunological kinetics of severe acute respiratory syndrome coronavirus 2 infection and diagnostic performance of serological assays for coronavirus disease 2019: an analysis of global reports.

As the coronavirus disease 2019 (COVID-19) pandemic continues to rise and second waves are reported in some countries, serological test kits and strips are being considered to scale up an adequate laboratory response. This study provides an update on the kinetics of humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and performance characteristics of serological protocols (lateral flow assay [LFA], chemiluminescence immunoassay [CLIA] and ELISA) used for evaluations of recent and past SARS-CoV-2 infection. A thorough and comprehensive review of suitable and eligible full-text articles was performed on PubMed, Scopus, Web of Science, Wordometer and medRxiv from 10 January to 16 July 2020. These articles were searched using the Medical Subject Headings terms 'COVID-19', 'Serological assay', 'Laboratory Diagnosis', 'Performance characteristics', 'POCT', 'LFA', 'CLIA', 'ELISA' and 'SARS-CoV-2'. Data from original research articles on SARS-CoV-2 antibody detection ≥second day postinfection were included in this study. In total, there were 7938 published articles on humoral immune response and laboratory diagnosis of COVID-19. Of these, 74 were included in this study. The detection, peak and decline period of blood anti-SARS-CoV-2 IgM, IgG and total antibodies for point-of-care testing (POCT), ELISA and CLIA vary widely. The most promising of these assays for POCT detected anti-SARS-CoV-2 at day 3 postinfection and peaked on the 15th day; ELISA products detected anti-SARS-CoV-2 IgM and IgG at days 2 and 6 then peaked on the eighth day; and the most promising CLIA product detected anti-SARS-CoV-2 at day 1 and peaked on the 30th day. The most promising LFA, ELISA and CLIA that had the best performance characteristics were those targeting total SARS-CoV-2 antibodies followed by those targeting anti-SARS-CoV-2 IgG then IgM. Essentially, the CLIA-based SARS-CoV-2 tests had the best performance characteristics, followed by ELISA then POCT. Given the varied performance characteristics of all the serological assays, there is a need to continuously improve their detection thresholds, as well as to monitor and re-evaluate their performances to assure their significance and applicability for COVID-19 clinical and epidemiological purposes.

Sero-survey of measles virus antibodies among symptomatic children attending Abuja Teaching Hospital, Nigeria.

Background: Nigeria is one of the countries with a high prevalence of measles outbreak in children under 5 years old, despite a history of vaccination. This study aims to determine the prevalence of anti-measles virus IgM and IgG among children under 5 years attending the University of Abuja Teaching Hospital (UATH), Gwagwalada, FCT Abuja, Nigeria. Materials and methods: Whole blood was collected, centrifuged, and serum anti-IgM and anti-IgG against measles virus was analysed using ELISA. Sociodemographic variables and vaccination history of subjects were obtained by interview-based questionnaires. Results: The overall anti-Measles virus IgG and IgM seroprevalences were 29.2% and 14.6%, respectively. The prevalence of measles IgG was significantly associated with the parent's employment status (X 2 =11.67, p=0.008). However, the prevalence of measles virus IgM was significantly associated with children's age (X 2 =16.62, p=0.002), parents' employment status and children's vaccination status (X 2 =7.72, p=0.02). Conclusion: A majority of study participants were not immunised against measles, and a significant number of participants had serological evidence of acute measles virus infection. There is a need for more concerted and massive measles vaccination of children.

Understanding the implications of SARS-CoV-2 re-infections on immune response milieu, laboratory tests and control measures against COVID-19.

Several months after the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cases of re-infection after recovery were reported. The extent and duration of protective immunity after SARS-CoV-2 infection is not fully understood. As such, the possibility of re-infection with SARS-CoV-2. Furthermore, cases of re-infection were mainly due to different variants or mutant SARS-CoV-2. Following the fast and pandemic-scale spread of COVID-19, mutations in SARS-CoV-2 have raised new diagnostic challenges which include the redesign of the oligonucleotide sequences used in RT-PCR assays to avoid potential primer-sample mismatches, and decrease sensitivities. Since the initial wave of the pandemic, some regions had experienced fresh outbreaks, predisposing people to be susceptible to SARS-CoV-2 re-infection. Hence, this article sought to offer detailed biology of SARS-CoV-2 re-infections and their implications on immune response milieu, diagnostic laboratory tests and control measures against COVID-19.

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges.

The incidence and case-fatality rates (CFRs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the etiological agent for Coronavirus Disease 2019 (COVID-19), have been rising unabated. Even though the entire world has been implementing infection prevention and control measures, the pandemic continues to spread. It has been widely accepted that preventive vaccination strategies are the public health measures for countering this pandemic. This study critically reviews the latest scientific advancement in genomics, replication pattern, pathogenesis, and immunopathology of SARS-CoV-2 infection and how these concepts could be used in the development of vaccines. We also offer a detailed discussion on the anticipated potency, efficacy, safety, and pharmaco-economic issues that are and will be associated with candidate COVID-19 vaccines.

Immunological and anti-oxidant profiles of malarial children in Abuja, Nigeria.

BACKGROUND: The clinical symptoms, cellular immune response, and serum cytokine homeostasis during falciparum malaria among children living in endemic regions depend on the parasite densities. This study aims to evaluate the CD4+ and CD8+ T cells, leucocytes subpopulations, IL-6, IL-10 and biomarkers of oxidative stress among children infected with varying grades of malaria attending the University of Abuja Teaching Hospital and National Hospital, Abuja, Nigeria. MATERIALS AND METHODS: This case-control study involved blood samples collected from 165 children (between 5 and 12 years). This comprised 45 children with mild malaria, 40 each with moderate, severe malaria and apparently healthy (control). Serum cytokines, ferritin, malonaldehyde (MDA), ascorbate, α-tocopherol levels were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Leucocytes differentials and CD4+/CD8+ T cells counts were enumerated by automated hematology analyzer and flow cytometry, respectively. RESULTS: All malarial children had only Plasmodium falciparum. The male to female ratio of children with mild malaria was 1.5:1 (mean ± SD age of 8.5 ± 1.9 years). However, other groups had 1:1 male to female ratio and mean ages of 9.2 ± 2.3, 9.8 ± 2.2, 8.5 ± 1.5 for children with moderate, severe malaria and control, respectively. There was a positive but not significant association of neutrophils and monocytes with the 3 grades of malaria parasitemia (p>0.05). There was a negative and significant correlation between severe malaria and lymphocyte count (p = 0.048; r = -0.647). However, there was positive and significant correlation between eosinophil with moderate (p = 0.03; r = 0.994) and severe malaria (p = 0.006; r = 0.825). There was a significant decline in serum ascorbate with increased malaria density (p<0.0001). However, there was no difference in the serum α-tocopherol concentration within the 4 groups of children (p = 0.182). Serum ferritin and MDA significantly elevated with an increase in malaria density (p<0.0001). There was a significant decline in CD4+ T and CD8+ T cells counts with an increase in malaria densities (p<0.0001). Serum IL-10 and IL-6 significantly elevated with increased malaria density (p<0.0001). CONCLUSION: Based on these findings, severe malaria was significantly associated with declined CD4+ and CD8+ T cell counts, upregulation of IL-6, and high serum levels of oxidative stress biomarkers.

Leucocytes and Th-associated Cytokine Profile of HIV-Leishmaniasis Co-Infected Persons Attending Abuja Teaching Hospital, Nigeria.

OBJECTIVE: T-helper cells (Th)-1& -2 cytokines homeostasis control or predict clinical outcome of infected persons, especially those with HIV /AIDS. This case-control study evaluated the leucocytes differentials, TNF-alpha, interleukin (IL)-2 and -10 levels among HIV infected persons with serological evidence of leishmaniasis attending University of Abuja Teaching Hospital, Nigeria. MATERIALS AND METHODS: Blood samples from 28 HIV infected persons who had Leishmania donovani rK39 and Immunoglobulin-G (IgG) positive (group 1), 30 age- & -sex matched HIV infected persons without Leishmania antibodies (group 2) and 30 apparently healthy persons without HIV and Leishmania antibodies (group 3). Full blood counts, TNF alpha, IL-2 and -10 levels were analyzed using automated hematology analyzer and ELISA, respectively. Structured questionnaires were used to collate biodata and clinical presentations of participants. RESULTS: Ten (35.7%) participants in group 1 were on ART, 15 (50%) in group 2 were on ART, while group 3 were ART naïve. There were significantly higher values in basophil (4.4±2.5%) and eosinophil counts (12.9±3.8%) in HIV/leishmania coinfected persons (p<0.005). However, other white cells subpopulation was significantly lower in HIV/leishmania co-infected participants (p<0.05). There was significantly reduced CD4+ T cell counts ([119±26 versus 348±63 versus 605±116 cells/mm3]), TNF-alpha ([36.82±8.21 versus 64.67±12.54 versus 254.98±65.59 pg/mL]) and IL-2 levels ([142.14±20.91 versus 507.6±84.42 versus 486.62±167.87 pg/mL]) among HIV/Leishmania co-infected participants compared to group 2 and group 3 participants, respectively. However, higher IL-10 level (80.35±14.57 pg/mL) was found in HIV/Leishmania co-infected participants as opposed to the HIV monoinfected (62.2±10.43 pg/mL) and apparently healthy persons (23.97±4.88 pg/mL) (p<0.001). CONCLUSION: Eosinophil, basophil counts and serum IL-10 level were high in HIV/Leishmania coinfected persons, demonstrating parasite-induced hypersensitivity and immunosuppression.

Phenotypic profile of pulmonary aspergillosis and associated cellular immunity among people living with human immunodeficiency virus in Maiduguri, Nigeria.

OBJECTIVE: Aspergillus causes many forms of pulmonary infectious diseases ranging from colonization (noninvasive) to invasive aspergillosis. This largely depends on the underlying host's lung health and immune status. Pulmonary aspergillosis (PA), especially the invasive form, occurs as opportunistic to human immunodeficiency virus (HIV) as a result of cluster of differentiation (CD)4+ lymphopenia. The majority of patients with comorbid HIV and aspergillosis go undiagnosed. This study aimed to isolate, identify the etiologies, and determine the prevalence of PA among HIV-infected persons with a productive cough (at least <2 weeks) at the HIV Clinics of the University of Maiduguri Teaching Hospital, Nigeria. MATERIALS AND METHODS: After ethical approval, three consecutive early morning sputum samples were collected from patients with negative tuberculosis results. The samples were individually inoculated onto Sabouraud dextrose agar supplemented with chloramphenicol and cycloheximide in duplicate for 7 days at 37°C and 25°C, respectively. The fungal isolates were examined morphologically and microscopically and identified using the standard biochemical reagents. CD4+ cell counts were performed using flow cytometry. Self-administered questionnaires were used to assess the patients data. All patients were antiretroviral naïve. RESULTS: The prevalence of PA was 12.7% in these 150 patients. Of the 19 fungal culture-positive individuals, Aspergillus fumigatus accounted for the highest proportion of the isolates (8, 42.1%) followed by Aspergillus niger (5, 26.3%), Aspergillus flavus (4, 21.1%), and Aspergillus terreus (2, 10.5%). Based on the assessment of functionality of cellular immunity, HIV participants who were negative for PA (131/150) had significantly higher mean ± standard deviation CD4 T-cell counts (245.65 ± 178.32 cells/mL) than those with aspergillosis (126.13 ± 105.27 cells/mL) (P = 0.0051). PA was relatively highest among patients with CD4+ cell counts <200 cells/mL (12. 34.3%) followed by those with CD4+ cell counts between 200 and 350 cells/mL (5, 9.6%) and least among those with CD4+ cell counts >350 cells/mL (2, 3.2%). The Chi-square test showed a significant association between the prevalence of PA and the CD4+ cell count, age, and gender (P < 0.05) but not with occupation or education level (P > 0.05). CONCLUSION: The findings from this study indicate that Aspergillus spp. is a significant etiology of acute productive cough in people living with HIV and this is related to the CD4+ cell count of coinfected persons.

Effects of Adalimumab, an Anti-tumour Necrosis Factor-Alpha (TNF-α) Antibody, on Obese Diabetic Rats.

BACKGROUND: Diabetes mellitus (DM) represents a major health problem worldwide. Recent studies have confirmed that obesity is a state of chronic inflammation that is characterised by increased concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and other inflammatory markers. It has been reported that increased TNF-α and IL-6 cause an immunological disturbance in DM. In the present study, the levels of fasting glucose, TNF-α and IL-6 were estimated in order to determine whether adalimumab can improve the glucose levels in obese diabetic rats. MATERIALS AND METHODS: Twenty-eight Wistar rats were divided into four groups: obese + diabetes + adalimumab (group 1), obese + diabetes (group 2), obese (group 3) and normal control (group 4), respectively (n = seven per group). Obesity was induced by feeding the rats in groups 1, 2 and 3 with a high-fat diet for four weeks. Some 30 mg/kg of streptozotocin (STZ) was administered to groups 1 and 2 so as to induce diabetes. Adalimumab was administered at a rate of 50 mg/kg to group 1 following the induction of diabetes. The fasting glucose, TNF-α and IL-6 concentrations were determined. RESULTS: A significant decrease was observed in the glucose levels of the treated rats (6.91 [0.11] mmol/L) when compared to those of the untreated rats (15.43 [0.44] mmol/L) (P < 0.001). The TNF-α levels were lower in group 1 (20.71 [0.35] ng/L) than in groups 2 (37.90 [0.27] ng/L) and 3 (25.89 [0.12] ng/L) (P < 0.001), although they were higher when compared to the levels seen in group 4 (12.44 [0.38] ng/L) (P < 0.001). The IL-6 concentrations were found to be elevated in groups 1 (22.89 [0.45] ng/L), 2 (21.00 [0.40] ng/L) and 3 (31.80 [1.32] ng/L) when compared to the levels seen in group 4 (18.70 [0.37] ng/L) (P < 0.001), although they were lower in group 1 (22.89 [0.45] ng/L) than in group 3 (31.80 [1.32] ng/L) (P < 0.001). CONCLUSION: Adalimumab reduced the glucose and TNF-α levels of diabetic rats, which indicates that it has a therapeutic effect in terms of controlling the blood glucose.