Prepandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: Systematic review and meta-analysis.

OBJECTIVES: To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations. METHODS: We performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. RESULTS: In total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity. CONCLUSION: Prepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence.

Transparency in Infectious Disease Research: Meta-research Survey of Specialty Journals.

BACKGROUND: Infectious diseases carry large global burdens and have implications for society at large. Therefore, reproducible, transparent research is extremely important. METHODS: We evaluated transparency indicators (code and data sharing, registration, and conflict and funding disclosures) in the 5340 PubMed Central Open Access articles published in 2019 or 2021 in the 9 most cited specialty journals in infectious diseases using the text-mining R package, rtransparent. RESULTS: A total of 5340 articles were evaluated (1860 published in 2019 and 3480 in 2021 [of which 1828 were on coronavirus disease 2019, or COVID-19]). Text mining identified code sharing in 98 (2%) articles, data sharing in 498 (9%), registration in 446 (8%), conflict of interest disclosures in 4209 (79%), and funding disclosures in 4866 (91%). There were substantial differences across the 9 journals: 1%-9% for code sharing, 5%-25% for data sharing, 1%-31% for registration, 7%-100% for conflicts of interest, and 65%-100% for funding disclosures. Validation-corrected imputed estimates were 3%, 11%, 8%, 79%, and 92%, respectively. There were no major differences between articles published in 2019 and non-COVID-19 articles in 2021. In 2021, non-COVID-19 articles had more data sharing (12%) than COVID-19 articles (4%). CONCLUSIONS: Data sharing, code sharing, and registration are very uncommon in infectious disease specialty journals. Increased transparency is required.

Clinical Spectrum, Radiological Findings, and Outcomes of Severe Toxoplasmosis in Immunocompetent Hosts: A Systematic Review.

BACKGROUND: Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening. METHODS: We performed a systematic review of severe toxoplasmosis cases in immunocompetent patients to gain insight into the epidemiology, clinical characteristics, radiological findings, and outcomes of these cases. We classified severe toxoplasmosis as cases with the symptomatic involvement of target organs (the lungs, central nervous system (CNS), and heart), disseminated disease, prolonged disease (>3 months), or a fatal outcome. Our primary analysis focused on cases published from 1985-2022 to avoid confounding with cases in AIDS patients. RESULTS: We identified 82 pertinent articles (1985-2022) with a total of 117 eligible cases; the top five countries for these cases were French Guiana (20%), France (15%), Colombia (9%), India (9%), and Brazil (7%). Overall, 44% (51/117) of cases had pulmonary involvement, 39% (46/117) CNS, 31% (36/117) cardiac, 24% (28/117) disseminated disease, 2% (2/117) had prolonged disease, and 8% (9/117) of patients died. More than one organ was involved in 26% (31/117) of cases. Eighty-four percent (98/117) of cases occurred in the context of a recent acute primary Toxoplasma infection; for the remaining, the exact timing of infection was unclear. Genotyping data were very sparse. Among those reporting genotyping data, 96% (22/23) were caused by atypical non-type II strains; one case was caused by a type-II strain. Only half of the cases reported risk factors. The most common risk factors were eating raw/undercooked meat or eating game meat (47% (28/60)), drinking untreated water (37% (22/60)), or living in a toxoplasmosis high-prevalence area (38% (23/60)). For the 51 pulmonary cases, the main clinical presentation was pneumonia or pleural effusions in 94% (48/51) and respiratory failure in 47% (24/51). For the 46 CNS cases, the main clinical presentation was encephalitis in 54% (25/46), meningitis in 13% (6/46), focal neurologic findings in 24% (11/46), cranial nerve palsies in 17% (8/46), Guillain-Barre syndrome or Miller Fisher syndrome in 7% (3/46), and Brown-Sequard syndrome in 2% (1/46) of cases; more than one clinical manifestation could also be present. Among the 41 CNS cases reporting the CNS imaging findings, 68% (28/41) had focal supratentorial lesions and 7% (3/41) had focal infratentorial lesions. Brain abscess-like/mass-like lesions were seen in 51% (21/41) of cases. For the 36 cardiac cases, the main clinical presentation was myocarditis in 75% (27/36), pericarditis in 50% (18/36), heart failure and/or cardiogenic shock in 19% (7/36), and cardiac arrhythmias in 22% (8/36); more than one manifestation could also be present. Illness was critical in 49% (44/90) of cases intensive care unit care was needed in 54% (29/54) of cases among those reporting this information, and 9 patients died. CONCLUSION: The diagnosis of severe toxoplasmosis in immunocompetent hosts can be challenging. Toxoplasmosis should be considered in the differential diagnosis of immunocompetent patients presenting with severe illness of unclear etiology with pulmonary, cardiac, CNS, or multiorgan involvement/failure, or prolonged febrile illness, even in the absence of common exposure risk factors or common manifestations of toxoplasmosis (e.g., fever, mononucleosis-like illness, lymphadenopathy, and chorioretinitis). Fatal outcomes can also rarely occur in immunocompetent patients. Prompt initiation of anti-Toxoplasma treatment can be lifesaving.

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review.

OBJECTIVE: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. METHODS: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias. RESULTS: 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of 'post-COVID syndrome' and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias. CONCLUSIONS: The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.

Differential COVID-19 infection rates in children, adults, and elderly: Systematic review and meta-analysis of 38 pre-vaccination national seroprevalence studies.

Background: Debate exists about whether extra protection of elderly and other vulnerable individuals is feasible in COVID-19. We aimed to assess the relative infection rates in the elderly vs the non-elderly and, secondarily, in children vs adults. Methods: We performed a systematic review and meta-analysis of seroprevalence studies conducted in the pre-vaccination era. We identified representative national studies without high risk of bias through SeroTracker and PubMed searches (last updated May 17, 2022). We noted seroprevalence estimates for children, non-elderly adults, and elderly adults, using cut-offs of 20 and 60 years (or as close to these ages, if they were unavailable) and compared them between different age groups. Results: We included 38 national seroprevalence studies from 36 different countries comprising 826 963 participants. Twenty-six of these studies also included pediatric populations and twenty-five were from high-income countries. The median ratio of seroprevalence in elderly vs non-elderly adults (or non-elderly in general, if pediatric and adult population data were not offered separately) was 0.90-0.95 in different analyses, with large variability across studies. In five studies (all in high-income countries), we observed significant protection of the elderly with a ratio of <0.40, with a median of 0.83 in high-income countries and 1.02 elsewhere. The median ratio of seroprevalence in children vs adults was 0.89 and only one study showed a significant ratio of <0.40. The main limitation of our study is the inaccuracies and biases in seroprevalence studies. Conclusions: Precision shielding of elderly community-dwelling populations before the availability of vaccines was indicated in some high-income countries, but most countries failed to achieve any substantial focused protection. Registration: Open Science Framework (available at: https://osf.io/xvupr).

Age-stratified infection fatality rate of COVID-19 in the non-elderly population.

The largest burden of COVID-19 is carried by the elderly, and persons living in nursing homes are particularly vulnerable. However, 94% of the global population is younger than 70 years and 86% is younger than 60 years. The objective of this study was to accurately estimate the infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.034% (interquartile range (IQR) 0.013-0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036-0.119%) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.002% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.123% at 50-59 years, and 0.506% at 60-69 years. IFR increases approximately 4 times every 10 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.

Toxoplasmosis and Schizophrenia: A Systematic Review and Meta-Analysis of Prevalence and Associations and Future Directions.

Background: A potential link between toxoplasmosis with schizophrenia (SCZ) has been extensively studied over the past 2 decades. Our study was aimed to determine whether, beyond an association, the field is primed for randomized clinical trials of anti-Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ. Methods: We performed a methodological appraisal of toxoplasmosis-SCZ association studies, a meta-analysis, and a compilation of claims and pathophysiologic hypotheses. Results: We analyzed 66 studies with 11,540 patients with SCZ and 69,491 controls. For patients with SCZ, 54 studies targeted Toxoplasma-IgG seropositivity, 18 targeted Toxoplasma-IgG serointensity, and 17 targeted Toxoplasma-IgM seropositivity. For SCZ-phenotypes, 26 targeted Toxoplasma-IgG seropositivity, six targeted Toxoplasma-IgG serointensity, and three targeted Toxoplasma-IgM seropositivity. Two-thirds of these studies reported a positive association. Statistically significant associations with SCZ were reported in 31/54 studies, 11/18 studies, and 3/17 studies. Significant associations with SCZ-phenotypes were reported in 20/26 studies, 2/6 studies, and 0/3 studies, respectively. Toxoplasma-IgG seropositivity increased the odds of SCZ (OR = 1.91; 95% CI: 1.61-2.27). Heterogeneity across studies was large (I 2 = 80.03%). Adjusted analyses for at least age and socioeconomic status/place of residence were done in 17 studies; temporality was addressed only in 4. Conclusion: A large number of observational studies revealed a modest to large association between toxoplasmosis and SCZ. Although important methodological biases were identified, further association studies are unlikely to change this association and are not justified. It is time to test this association in randomized double-blind placebo-controlled clinical trials of first line anti-Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ.

Multisystem Inflammatory Syndrome in Adults and Severe Toxoplasmosis: Similar Clinical Presentations, Potentially Severe Outcomes.

We report a case of a 21-year-old previously healthy man who developed severe toxoplasmosis with chorioretinitis and myositis 2 months after receiving corticosteroids for presumed multisystem inflammatory syndrome in adults, in the setting of a recently acquired acute Toxoplasma infection, likely during a trip to Latin America.

Infectious Diseases-Related Hospitalizations During Oral Polio Vaccine (OPV) and Non-OPV Immunization Periods: An Empirical Evaluation of all Hospital Discharges in California (1985-2010).

BACKGROUND: Live attenuated vaccines such as oral polio vaccine (OPV) can stimulate innate immunity and may have off-target protective effects on other pathogens. We aimed to address this hypothesis by examining changes in infectious diseases (ID)-related hospitalizations in all hospital discharges in California during OPV (1985-1996) and non-OPV immunization periods (2000-2010). METHODS: We searched the Office of Statewide Health Planning and Development database for all hospital discharges with any ID-related discharge diagnosis code during 1985-2010. We compared the proportion of ID-related hospitalizations (with at least 1 ID-related discharge diagnosis) among total hospitalizations during OPV immunization (1985-1996) versus non-OPV immunization (2000-2010) periods. RESULTS: There were 19 281 039 ID-related hospitalizations (8 464 037 with an ID-related discharge diagnosis as the principal discharge diagnosis for the hospitalization) among 98 117 475 hospitalizations in 1985-2010; 9 520 810 ID hospitalizations/43 456 484 total hospitalizations in 2000-2010 versus 7 526 957/43 472 796 in 1985-1996. The risk ratio for ID-related hospitalizations in 2000-2010 versus 1985-1996 was 1.27 (95% confidence interval [CI], 1.26-1.27) for all diagnoses and 1.15 (95% CI: 1.15-1.16) for principal diagnoses. Increases also existed in the proportion of lower respiratory and gastrointestinal infections. DISCUSSION: The proportion of ID-related hospitalizations was lower in the OPV immunization period compared to the period after OPV was discontinued. When focused only on hospitalizations with ID as the principal discharge diagnosis, the signal remained significant but was smaller. These findings require replication in additional studies.