Effect of and Interventions in Prevention and Management of Maternal Anemia in the Advent of COVID-19 (preprint)

Background There were many unknowns for pregnant women during the COVID-19 pandemic. Most of these could have been silent however lethal and anemic conditions could escalate the worsening of pregnancy outcomes. Existing evidence indicate that, array of factors is associated with the ability of compromising maternal anemia, some directly and others indirectly. Objective This review aimed at ascertaining the pooled effect of several anemia interventions. Specifically, the aim of this study was to establish if pregnancy status is associated with COVID-19 severity characterized by a cytokine storm. Methods We searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to studies suitable for inclusion in this meta-analysis. Studies examining women of reproductive age on any maternal anemia intervention were included. The risk of bias was assessed using the Cochrane risk of bias tool. Review Manager 5.4.1 was used to calculate rate ratios (RRs) with 95% CIs, which were depicted using forest plots. Quantitative variables were summarized in total numbers and percentages. The effect on prevention, control, management and or treatment of anemia was calculated and compared between the intervention and the comparator arms. Heterogeneity was evaluated with the Cochran Q statistic and Higgins test. Results A total of 11 articles including data for 6,129 were included. With sensitivity analysis, the interventions had a utility of 39% on maternal anemia prevention and management (random effects model RR 0.61, 95% CI 0.43, 0.87; P = 0.006) (X-squared 6=286.98, P<.00001; I-squared=97%). All the interventions against maternal anemia showed an effect of 17% (fixed-effect model RR 0.83, 95% CI 0.79-0.88; P<.00001) (X-squared 7;24=2.93, P=0.57;I-squared = 0%). Education to pregnant women showed a 28% effect (RR 0.72 95% CI 0.58, 0.89), medicinal administration 19% (RR 0.81 95% CI 0.73, 0.90), iron supplementation 17% (RR 0.83 95% CI 0.75, 0.92) and I.V Ferric Carboxy-maltose 15% (RR 0.85 95% CI 0.74, 0.97) (I-squared = 0%). Interventions in African region had a higher (16%) and significant effect compared to other regions (fixed-effects model RR 0.84, 95% CI 0.79-0.89; P<.001) (X-squared 7;25=176.53, P<.00001;I-squared = 7%). Multiple center studies had a significant predictive effect (16%) compared to single center studies (fixed-effects model RR 0.84, 95% CI 0.79-0.89; P<.00001)(967;25=176.53, P<.00001; I-squared=97%) .The year 2020 recorded the highest effect of maternal anemia interventions at 28% (random-effects model RR 0.72, 95% CI 0.67-0.78; P<.00001) (967;23=167.34, P<.00001; I-squared =98%) Conclusion In the advent of COVID-19, maternal anemia interventions were compromised demonstrated by a low effectiveness trend from the year 2020 to the year 2022. During this period, even the most effective and recommended interventions against maternal anemia were somehow affected.

Effect of HIV disease and the associated moderators on COVID-19 related Mortality (preprint)

Introduction Established predictors for COVID 19 related mortalities are diverse. The impact of these several risk factors on coronavirus mortality have been previously reported in several metaanalyses limited by small sample sizes and premature data. The objective of this systematic review and metaanalysis was to evaluate the updated evidence on the risk of COVID 19 related mortality with HIV serostatus using published data, and a metaregression to account for possible moderators Method Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID 19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty two studies with a total of 19,783,097 patients detailing COVID 19 related mortality were included. To pool the estimate, a random effects model with risk ratio as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register. Results The findings were consistent in stating the contribution of HIV infection for COVID-19 related mortality.The cumulative COVID-19 related mortality was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related mortality [RR =1.19, 95% CI (1.02, 1.39) (P=0.00001)] with substantial heterogeneity (I squared > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22. Multiple Centre studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092, 1.559) (P = 0.003)], similar to studies conducted in America (RR=1.422, 95% CI 1.233, 1.639) and South Africa (RR=202;1.123, 95% CI 1.052, 1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I squared = 0%)] and mechanical ventilation [(P=0.04) (I squared = 0%)] which are predictors of COVID-19 severity prior to death. Furthermore, risk of COVID 19 related mortality is influenced by the region of study (R squared = 0.60). The variance proportion explained by covariates was significant(I squared = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R squared = 0.67). Conclusion Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID 19 mortality, which might be modulated by the regions. We believe the updated data further will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)

Effect of HIV infection on COVID-19 Cytokine Release Syndrome and Mortality (preprint)

Introduction: Established predictors for COVID-19 related mortalities are diverse, with cytokine release syndrome (CRS), a key intermediator to the case fatalities being dominant and multi-faceted. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta‐analyses limited by small sample sizes and premature data, and CRS not fully being accounted for. The objective of this systematic review and meta-analysis was to evaluate the evidence on the risk of COVID-19 related CRS and mortality with HIV serostatus using published data, and a meta-regression to account for possible covariates. Method: Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID-related mortality and eleven with a total of 2,005,274 were included. To pool the estimate, a random-effects model with risk ration as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register. Results: The findings were consistent in stating the contribution of HIV infection for COVID-19 related CRS and mortality. The cumulative COVID-19 related mortality and CRS was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) and 837(4.6%), 48026 (2.4%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related CRS and mortality [RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)] and [RR =1.19, 95% CI (1.02 -1.39) (P=0.00001)] respectively, both with substantial heterogeneity (I2 > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22 and 0.67 to 3.29 for mortality and CRS respectively. MC studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092 -1.559) (P = 0.003)], similar to studies conducted in America (RR = 1.422, 95% CI 1.233–1.639) and South Africa (RR = 1.123, 95% CI 1.052–1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I² = 0%)] and mechanical ventilation [(P=0.04) (I² = 0%)] as parameters of CRS. Furthermore, risk of COVID-19 related CRS is influenced by the year a study was conducted (R² = 0.55) and the region (R² = 0.11) same for mortality (R² = 0.60). The variance proportion explained by covariates was significant for CRS (I² = 86.5%, Q = 73.99, df = 10, P = 0.0000) (R² = 0.78) and mortality (I² = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R² = 0.67). Conclusion: Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID-19 – CRS and mortality, which might be modulated by regions, study setting and year. Risk for ICU admission and mechanical ventilation are the key indicators of CRS. We believe the updated data further anchoring CRS will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)

Correlation between Pregnancy Status and Severe Corona-Virus Disease Characterized by Cytokine Storm: Systematic Review and Meta-Analysis (preprint)

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2) that identified first in Wuhan, China, in December 2019, rapidly spreading to the rest of the globe, becoming a pandemic. Some studies have eluded to an association between pregnancy status and severe COVID-19 cytokine storm, some, in contrast, have demonstrated such. The aim of the current study was to find the relationship between pregnancy status and clinical COVID-19 severity characterized by cytokine storm through a systematic review and meta-analysis approach. Methods We searched Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. The COVID-19 severity characterized by cytokine storm was described using parameters such as; Intensive Care Unit Admission, Invasive Mechanical Ventilation, Mechanical Ventilation, Hospital Admission, Pro and Inflammatory cytokine levels, consolidation on chest CT scan, pulmonary infiltration, extreme fevers as characteristic of cytokine storm, syndromic severity, higher neutrophil count indicative of cytokine storm and severe COVI-19 presentation. Results A total of 17 articles detailing 840332 COVID-19 women were included. Our meta-analysis revealed a relationship between positive pregnancy status and severe COVID-19 cytokine storm case (random effect model, OR=2.47; 95% CI: 1.63-3.73; P < 0.0001), with a cumulative incidence of 6432 (14.1%) among the pregnant women with COVID-19 and 24352 (3.1%) among the non-pregnant women with COVI-19. Further to this, we found that the sub-analysis between Single Centre and Multiple Centre studies demonstrated seemingly the same as heterogeneity (I 2 = 72 and (I 2 = 98), respectively. Sensitivity analysis on each sub-group revealed that pregnancy was significantly related to severe COVID-19 with cytokine storm from single Centre studies, (fixed effect model, OR= 3.97; 95% CI: 2.26-6.95; P< 0.00001) with very low heterogeneity (I 2 = 2 %; P = 0.42). Conclusion Being pregnant is clearly associated with experiencing a severe COVID-19 characterized by a cytokine storm. The SARS-COV-2 epidemic should serve as an impetus for pregnant women diagnosed with COVID-19, and map out salient risk factors associated with its severity. The trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021242011.