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1.
Med Rev (Berl) ; 2(1): 66-88, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1879341

ABSTRACT

With the presence of Coronavirus Disease 2019 (COVID-19) asymptomatic infections detected, their proportion, transmission potential, and other aspects such as immunity and related emerging challenges have attracted people's attention. We have found that based on high-quality research, asymptomatic infections account for at least one-third of the total cases, whereas based on systematic review and meta-analysis, the proportion is about one-fifth. Evaluating the true transmission potential of asymptomatic cases is difficult but critical, since it may affect national policies in response to COVID-19. We have summarized the current evidence and found, compared with symptomatic cases, the transmission capacity of asymptomatic individuals is weaker, even though they have similar viral load and relatively short virus shedding duration. As the outbreak progresses, asymptomatic infections have also been found to develop long COVID-19. In addition, the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge. Nevertheless, as asymptomatic infections transmit the SARS-CoV-2 virus silently, they still pose a substantial threat to public health. Therefore, it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible; meanwhile, management of them is also a key point in the fight against COVID-19 community transmission. The different management of asymptomatic infections in various countries are compared and the experience in China is displayed in detail.

2.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1863910

ABSTRACT

The emergence of SARS-CoV-2 variants that have greater transmissibility and resistance to neutralizing antibodies has increased the incidence of breakthrough infections. We show that breakthrough infection increases neutralizing antibody titers to varying degrees depending on the nature of the breakthrough variant and the number of vaccine doses previously administered. Omicron breakthrough infection resulted in neutralizing antibody titers that were the highest across, particularly against omicron.

3.
EClinicalMedicine ; 46: 101373, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1850961

ABSTRACT

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes. Methods: A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not). Findings: Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I2  = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 (N = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I2  = 78%; N = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I2  = 26%), or an increased probability of intensive care unit (ICU) admission (N = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I2  = 82% ; N = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I2  = 60%), requiring mechanical ventilation (N = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I2  = 63%; N = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I2  = 66%), or administration of supplemental oxygen (N = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I2  = 63%; N = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I2  = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen (N = 5, OR = 1.09, 95% CI: 0.50 to 2.39; N = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor (N = 4, OR = 0.62, 95% CI: 0.35 to 1.11; N = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death. Interpretation: Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings. Funding: There was no funding source for this study.

4.
BMC Med Res Methodol ; 22(1): 89, 2022 04 03.
Article in English | MEDLINE | ID: covidwho-1846794

ABSTRACT

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.


Subject(s)
COVID-19 , COVID-19/epidemiology , Child , Disease Outbreaks , Guidelines as Topic , Humans , Public Health
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336206

ABSTRACT

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.

6.
Nature ; 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1805634

ABSTRACT

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

7.
EClinicalMedicine ; 46:101373-101373, 2022.
Article in English | EuropePMC | ID: covidwho-1782304

ABSTRACT

Background There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes. Methods A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not). Findings Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I2 = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 (N = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I2 = 78%;N = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I2 = 26%), or an increased probability of intensive care unit (ICU) admission (N = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I2 = 82% ;N = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I2 = 60%), requiring mechanical ventilation (N = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I2 = 63%;N = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I2 = 66%), or administration of supplemental oxygen (N = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I2 = 63%;N = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I2 = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen (N = 5, OR = 1.09, 95% CI: 0.50 to 2.39;N = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor (N = 4, OR = 0.62, 95% CI: 0.35 to 1.11;N = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death. Interpretation Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings. Funding There was no funding source for this study.

8.
Immunity ; 55(6): 998-1012.e8, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1778212

ABSTRACT

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Humans , SARS-CoV-2
9.
Eur J Pediatr ; 181(5): 2135-2146, 2022 May.
Article in English | MEDLINE | ID: covidwho-1699807

ABSTRACT

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.


Subject(s)
COVID-19 , Adolescent , COVID-19/complications , COVID-19/drug therapy , Child , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/adverse effects , Respiration, Artificial , Systemic Inflammatory Response Syndrome
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321377

ABSTRACT

Background: The prognosis of children and adolescents with COVID-19 obtain increasing attention worldwide. This study provides the first systematic review and meta-analysis to identify risk factors which predict poor prognosis in this group.Methods: Electronic databases from inception to March, 2021 were searched for cohort studies, case-control studies and case series that investigated risk factors for poor prognosis of children and adolescents with COVID-19. We estimated the summary effect size by use of random-effects models and the 95% confidential interval (CI).Findings: We identified 33 studies, comprising 32,225 individuals. The risk of bias were generally high. In children and adolescents with COVID-19, risk of death was significantly increased in patients with MIS-C complication (odds ratio [OR]=58.00, 95% CI 6.39 to 526.79) and in need for intensive care (OR=15.25, 95% CI 1.98 to 117.44). Congenital heart disease (OR=2.90, 95% CI 1.26 to 6.67), chronic pulmonary disease (OR=3.45, 95% CI 1.47 to 8.07), and gastrointestinal symptoms (OR=2.11, 95% CI 1.43 to 3.12) increased the odds to be admitted to ICU;MIS-C complication (OR=70.00, 95% CI 6.51 to 752.27) and neurological diseases (OR=2.51, 95% CI 1.03 to 6.15) increased the odds of respiratory support;neurological diseases (OR=4.59, 95% CI 1.99 to 10.61), obesity (OR=2.51, 95% CI 2.02 to 3.12), C-reactive protein (CRP) level ≥80mg/L (OR=11.70, 95% CI 4.37 to 31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76 to 236.44) on admission increased the odds of progression to severe/critical disease.Interpretation: Very low to moderate quality evidence found that MIS-C, congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, and gastrointestinal symptoms, in need for intensive care, elevated CRP and D-dimer are risk factors for poor prognosis in children and adolescents with COVID-19.Funding: None.Declaration of Interests: The authors declare that they have no competing interests.

11.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327676

ABSTRACT

The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals. The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain. The 3 rd mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection. Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses. We find that the 3 rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2 nd vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2 nd vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3 rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3 rd dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

12.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327582

ABSTRACT

Vaccination and infection by viral variants are shaping population immunity to SARS-CoV-21 and breakthrough infections of vaccinated or previously infected individuals have become common as variants evade preexisting immunity. Omicron (B.1.1.529) is highly resistant to plasma neutralizing antibodies elicited by infection with prior variants and the 2-dose mRNA vaccination regimens. However, vaccination after infection or a third mRNA vaccine dose elicit high levels of neutralizing antibodies that can also neutralize omicron to a degree2-4. We compared neutralizing antibody titers in 54 individuals that had received 2 or 3 doses of mRNA vaccines and had experienced breakthrough infection with SARS-CoV-2 variants.

13.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327330

ABSTRACT

Summary SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain. In contrast, most neutralizing antibodies to NTD characterized to date bind to a single supersite, however these antibodies were obtained by methods that were not NTD specific. Here we use NTD specific probes to focus on anti-NTD memory B cells in a cohort of pre-omicron infected individuals some of which were also vaccinated. Of 275 NTD binding antibodies tested 103 neutralized at least one of three tested strains: Wuhan-Hu-1, Gamma, or PMS20, a synthetic variant which is extensively mutated in the NTD supersite. Among the 43 neutralizing antibodies that were further characterized, we found 6 complementation groups based on competition binding experiments. 58% targeted epitopes outside the NTD supersite, and 58% neutralized either Gamma or Omicron, but only 14% were broad neutralizers. Three of the broad neutralizers were characterized structurally. C1520 and C1791 recognize epitopes on opposite faces of the NTD with a distinct binding pose relative to previously described antibodies allowing for greater potency and cross-reactivity with 7 different variants including Beta, Delta, Gamma and Omicron. Antibody C1717 represents a previously uncharacterized class of NTD-directed antibodies that recognizes the viral membrane proximal side of the NTD and SD2 domain, leading to cross-neutralization of Beta, Gamma and Omicron. We conclude SARS-CoV-2 infection and/or Wuhan-Hu-1 mRNA vaccination produces a diverse collection of memory B cells that produce anti-NTD antibodies some of which can neutralize variants of concern. Rapid recruitment of these cells into the antibody secreting plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants including omicron.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325364

ABSTRACT

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

15.
J Clin Epidemiol ; 144: 163-172, 2022 04.
Article in English | MEDLINE | ID: covidwho-1670681

ABSTRACT

OBJECTIVE: To describe the current status of COVID-19 vaccine guidelines. STUDY DESIGN AND SETTING: We searched databases, Google and guideline platforms to retrieve COVID-19 vaccine guidelines published between January 1, 2020 and July 8, 2021. We worked in pairs to identify the eligible guidelines and extract data of whether the methodology, funding, and conflict of interests were assessed/reported, and so on. Results were presented descriptively. RESULTS: A total of 106 COVID-19 vaccine guidelines were included. In the first half of 2021, on average 15 guidelines were published every month. Fifty (47.2%) guidelines addressed the vaccination of people with specific medical conditions, and 18 (17.0%) guidelines focused on adverse effects after vaccination. Only 28 (26.4%) guidelines reported the methodology they used. Four (3.8%) of guidelines assessed both the quality of evidence and strength of recommendations; 42 (39.6%) and 65 (61.3%) guidelines reported their funding sources and conflict of interest, respectively. Most guidelines were published in English (n = 92, 86.8%). CONCLUSION: A high number of guidelines on COVID-19 vaccines have been published in the recent months, but most of them lack clear and transparent reporting of methodology, funding, and conflicts of interest. Rigorous methodological and reporting quality evaluation of these guidelines is needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Databases, Factual , Humans
17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296969

ABSTRACT

BACKGROUND The Omicron SARS-CoV-2 variant has spread internationally and is responsible for rapidly increasing case numbers. The emergence of divergent variants in the context of a heterogeneous and evolving neutralizing antibody response in host populations might compromise protection afforded by vaccines or prior infection. METHODS We measured neutralizing antibody titers in 169 longitudinally collected plasma samples using pseudotypes bearing the Wuhan-hu-1 or the Omicron variant or a laboratory-designed neutralization-resistant SARS-CoV-2 spike (PMS20). Plasmas were obtained from convalescents who did or did not subsequently receive an mRNA vaccine, or naive individuals who received 3-doses of mRNA or 1-dose Ad26 vaccines. Samples were collected approximately 1, 5-6 and 12 months after initial vaccination or infection. RESULTS Like PMS20, the Omicron spike protein was substantially resistant to neutralization compared to Wuhan-hu-1. In convalescent plasma the median deficit in neutralizing activity against PMS20 or Omicron was 30- to 60-fold. Plasmas from recipients of 2 mRNA vaccine doses were 30- to 180- fold less potent against PMS20 and Omicron than Wuhan-hu-1. Notably, previously infected or two-mRNA dose vaccinated individuals who received additional mRNA vaccine dose(s) had 38 to 154-fold and 35 to 214-fold increases in neutralizing activity against Omicron and PMS20 respectively. CONCLUSIONS Omicron exhibits similar distribution of sequence changes and neutralization resistance as does a laboratory-designed neutralization-resistant spike protein, suggesting natural evolutionary pressure to evade the human antibody response. Currently available mRNA vaccine boosters, that may promote antibody affinity maturation, significantly ameliorate SARS-CoV-2 neutralizing antibody titers.

18.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296284

ABSTRACT

Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies 1,2 . Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines 3,4 . In the absence of vaccination antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naïve individuals 2,5-8 . The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover, and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in variants of concern 4,9 . In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.

19.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294471

ABSTRACT

Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern 1 . As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested 1, 2 . Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer- BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naïve individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naïve individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with breadth equivalent to those obtained by vaccinating convalescent individuals.

20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292232

ABSTRACT

Introduction: The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. Methods: : We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. Results: : A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 54.7% (95%CI, 10.3% to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2% to 10.1%) died, 27.0% (95%CI, 0% to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. Conclusions: : Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

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