Abstract Introduction This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis. Methods PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection. Results 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia— 0.51 (95% CI: 0.37,0.65), Europe— 0.44 (95% CI: 0.32,0.56), and North America— 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]). Discussion This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review

Abstract Background This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis. Methods PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection. Results Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39–.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44–.63) and 0.34 (95% CI, .25–.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37–.65), Europe (0.44; 95% CI, .32–.56), and United States of America (0.31; 95% CI, .21–.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26–.49), 0.25 (95% CI, .15–.38), 0.32 (95% CI, .14–.57), and 0.49 (95% CI, .40–.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17–.30), followed by memory problems (0.14; 95% CI, .10–.19). Conclusions This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system. 

OUP accepted manuscript

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation. 

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Human genetic and immunological determinants of critical COVID-19 pneumonia

Systematic review of empirical studies comparing the effectiveness of non-pharmaceutical interventions against COVID-19.

Introduction Vaccination has greatly reduced the burden of infectious diseases Only clean water, also considered to be a basic human right, performs better (1) Paradoxically, a vociferous antivaccine lobby thrives today in spite of the undeniable success of vaccination programmes against formerly fearsome diseases that are now rare in developed countries (2) Understandably, vaccine safety gets more public attention than vaccination effectiveness, but independent experts and WHO have shown that vaccines are far safer than therapeutic medicines (2,3) Modern research has spurred the development of less reactogenic products, such as acellular pertussis vaccines and rabies vaccines produced in cell culture Today, vaccines have an excellent safety record and most "vaccine scares" have been shown to be false alarms (4,5) Misguided safety concerns in some countries have led to a fall in vaccination coverage, causing the re-emergence of pertussis and measles (6) Putative vaccine safety issues are commonly reported while reviews of vaccine benefits are few A Medline search over the past five years using the keywords "vaccine risks" scored approximately five times as many hits (2655 versus 557) as a Medline search using "vaccine benefits" as keywords (7) This reflects the fact that negative aspects of vaccination get much more publicity than positive aspects How one addresses the antivaccine movement has been a problem since the time of Jenner The best way in the long term is to refute wrong allegations at the earliest opportunity by providing scientifically valid data This is easier said than done, because the adversary in this game plays according to rules that are not generally those of science This issue will not be further addressed in this paper, which aims to show how vaccines are valuable to both individuals and societies, to present validated facts, and to help redress adverse perceptions Without doubt, vaccines are among the most efficient tools for promoting individual and public health and deserve better press (8) Disease control benefits Eradication Unless an environmental reservoir exists, an eradicated pathogen cannot reemerge, unless accidentally or malevolently reintroduced by humans, allowing vaccination or other preventive measures to be discontinued While eradication may be an ideal goal for an immunization programme, to date only smallpox has been eradicated, allowing discontinuation of routine smallpox immunization globally Potentially, other infectious diseases with no extrahuman reservoir can be eradicated provided an effective vaccine and specific diagnostic tests are available Eradication requires high levels of population immunity in all regions of the world over a prolonged period with adequate surveillance in place (9) The next disease targeted for eradication is polio, which is still a global challenge (10) Although high coverage with oral polio vaccine (OPV) has eliminated type 2 poliovirus globally, transmission of types 1 and 3 continues in limited areas in a few countries OPV-caused paralytic disease, directly or by reversion to virulence, and persistent vaccine-virus excretion in immunodeficient individuals are problems yet to be solved Global use of monovalent type 1 and type 30PV and inactivated polio vaccine (IPV) may eventually be required (10) Elimination Diseases can be eliminated locally without global eradication of the causative microorganism In four of six WHO regions, substantial progress has been made in measles elimination; transmission no longer occurs indigenously and importation does not result in sustained spread of the virus (11) Key to this achievement is more than 95% population immunity through a two-dose vaccination regimen Combined measles, mumps and rubella (MMR) vaccine could also eliminate and eventually eradicate rubella and mumps (11) Increasing measles immunization levels in Africa, where coverage averaged only 67% in 2004, is essential for eradication of this disease …

Vaccination Greatly Reduces Disease, Disability, Death and Inequity worldwide/La Vaccination Reduit Fortement la Morbidite, Les Incapacites, la Mortalite et Les Inegalites Dans L'ensemble Du monde/La Vacunacion Reduce Considerablemente la Morbilidad, Las Discapacidades, la Mortalidad Y Las Inequidades En Todo El Mundo

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.

https://www.pnas.org/content/pnas/118/34/e2109229118.full.pdf

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis.

BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%–50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%–6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%–3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%–6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%–3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.

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Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States.

The province of Ontario, Canada, has instituted indefinite school closures (SC) as well as other social distancing measures to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) pandemic. We sought to evaluate the effect of SC on reducing attack rate and the need for critical care during COVID-19 outbreaks, while considering scenarios with concurrent implementation of self-isolation (SI) of symptomatic cases. We developed an age-structured agent-based simulation model and parameterized it with the demographics of Ontario stratified by age and the latest estimates of COVID-19 epidemiologic characteristics. Disease transmission was simulated within and between different age groups by considering inter- and intra-group contact patterns. The effect of SC of varying durations on the overall attack rate, magnitude and peak time of the outbreak, and requirement for intensive care unit (ICU) admission in the population was estimated. Secondly, the effect of concurrent community-based voluntary SI of symptomatic COVID-19 cases was assessed. SC reduced attack rates in the range of 7.2–12.7% when the duration of SC increased from 3 to 16 weeks, when contacts among school children were restricted by 60–80%, and in the absence of SI by mildly symptomatic persons. Depending on the scenario, the overall reduction in ICU admissions attributed to SC throughout the outbreak ranged from 3.3 to 6.7%. When SI of mildly symptomatic persons was included and practiced by 20%, the reduction of attack rate and ICU admissions exceeded 6.3% and 9.1% (on average), respectively, in the corresponding scenarios. Our results indicate that SC may have limited impact on reducing the burden of COVID-19 without measures to interrupt the chain of transmission during both pre-symptomatic and symptomatic stages. While highlighting the importance of SI, our findings indicate the need for better understanding of the epidemiologic characteristics of emerging diseases on the effectiveness of social distancing measures.

/pdf/simulating-the-effect-of-school-closure-during-covid-19-5138n85l5o.pdf

Simulating the effect of school closure during COVID-19 outbreaks in Ontario, Canada.

Evidence has demonstrated that a new class of anti-diabetic drugs, sodium-glucose co-transporter 2 (SGLT2) inhibitors, could exert beneficial effects on atherosclerotic complications of diabetes. Atherosclerosis is widely accepted as an inflammatory disease. Therefore, we aimed to assess the direct anti-inflammatory effects of SGLT2 inhibitors dapagliflozin (DAPA) on two cell types involved in the process of atherogenesis. Human umbilical vein endothelial cells (HUVECs) and macrophages were exposed to DAPA and lipopolysaccharide (LPS 20 ng/mL) for 24 h under normal (5.5 mmol/L, NG) or high glucose (25 mmol/L, HG) conditions. Then, levels of TLR-4/p-NF-κB, inflammatory cytokines, inflammation-related miR-146a and miR-155 as well as alteration in the ratio of M1/M2 macrophage polarization was assessed. DAPA (0.5 μM) could significantly attenuate LPS-induced TLR-4 overexpression (23.9% and 33.1% under NG and HG conditions in HUVECs and 53.3% and 52.4% under NG and HG states in macrophages, respectively). NF-κB p65 phosphorylation was also significantly decreased to 30.1% under NG condition in HUVECs and 51.9% and 34.5% under NG and HG states in macrophages by 0.5 μM DAPA. Moreover, DAPA elevated expression levels of anti-inflammatory miR-146a, while values of miR-155 decreased in those cells. DAPA also caused a shift from inflammatory M1 macrophages toward M2-dominant macrophages. These data suggest that regardless of glucose concentrations, DAPA could exert direct anti-inflammatory effects, at least partly, by inhibiting the expression of TLR-4 and activation of NF-κB along with the secretion of pro-inflammatory mediators. 

Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages

Elaheh Abdollahi

Papers

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis.

Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States.

Simulating the effect of school closure during COVID-19 outbreaks in Ontario, Canada.

Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages

Importance of non-pharmaceutical interventions in the COVID-19 vaccination era: A case study of the Seychelles.