Many studies have shown that re-positive tests for SARS-CoV-2 by RT-PCR in recovered COVID-19 patients are very common. We aim to conduct this review to summarize the clinical and epidemiological characteristics of these patients and discuss the potential explanations for recurrences, the contagiousness of re-detectable positive SARS-CoV-2 virus, and the management of COVID-19 patients after discharge from hospital. The proportion of re-positive tests in discharged COVID-19 patients varied from 2.4 to 69.2% and persisted from 1 to 38 days after discharge, depending on population size, age of patients, and type of specimens. Currently, several causes of re-positive tests for SARS-CoV-2 in recovered COVID-19 patients are suggested, including false-negative, false-positive RT-PCR tests; reactivation; and re-infection with SARS-CoV-2, but the mechanism leading to these re-positive cases is still unclear. The prevention of re-positive testing in discharged patients is a fundamental measure to control the spread of the pandemic. In order to reduce the percentage of false-negative tests prior to discharge, we recommend performing more than two tests, according to the standard sampling and microbiological assay protocol. In addition, specimens should be collected from multiple body parts if possible, to identify SARS-CoV-2 viral RNA before discharge. Further studies should be conducted to develop novel assays that target a crucial region of the RNA genome in order to improve its sensitivity and specificity.

/pdf/recurrence-of-sars-cov-2-viral-rna-in-recovered-covid-19-1bmpraxmqo.pdf

Recurrence of SARS-CoV-2 viral RNA in recovered COVID-19 patients: a narrative review.

SARS-CoV-2 infections have been reported in all age groups including infants, children, and adolescents. However, the role of children in the COVID-19 pandemic is still uncertain. This systematic review of early studies synthesises evidence on the susceptibility of children to SARS-CoV-2 infection, the severity and clinical outcomes in children with SARS-CoV-2 infection, and the transmissibility of SARS-CoV-2 by children in the initial phases of the COVID-19 pandemic. A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published up to July 4th 2020 during the first wave of the SARS-CoV-2 outbreak using a standardised form and assessed quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. For studies included in the meta-analysis, we used a random effects model to calculate pooled estimates of the proportion of children considered asymptomatic or in a severe or critical state. We identified 2775 potential studies of which 128 studies met our inclusion criteria; data were extracted from 99, which were then quality assessed. Finally, 29 studies were considered for the meta-analysis that included information of symptoms and/or severity, these were further assessed based on patient recruitment. Our pooled estimate of the proportion of test positive children who were asymptomatic was 21.1% (95% CI: 14.0-28.1%), based on 13 included studies, and the proportion of children with severe or critical symptoms was 3.8% (95% CI: 1.5-6.0%), based on 14 included studies. We did not identify any studies designed to assess transmissibility in children and found that susceptibility to infection in children was highly variable across studies. Children's susceptibility to infection and onward transmissibility relative to adults is still unclear and varied widely between studies. However, it is evident that most children experience clinically mild disease or remain asymptomatically infected. More comprehensive contact-tracing studies combined with serosurveys are needed to quantify children's transmissibility relative to adults. With children back in schools, testing regimes and study protocols that will allow us to better understand the role of children in this pandemic are critical.

/pdf/children-s-role-in-the-covid-19-pandemic-a-systematic-review-4b2qd8h25t.pdf

Children's role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility.

Background There is recently a concern regarding the reinfection and reactivation of previously reCoVered coronavirus disease 2019 (CoVID-19) patients. Aim To summarize the recent findings and reports of CoVID-19 reinfection in patients previously reCoVered from the disease. Methods This study was a systematic review of current evidence conducted in August 2020. The authors studied the probable reinfection risk of novel coronavirus (CoVID-19). We performed a systematic search using the keywords in online databases. The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of this study and results. Results We reviewed 31 studies. Eight studies described reCoVered patients with reinfection. Only one study reported reinfected patients who died. In 26 studies, there was no information about the status of the patients. Several studies indicated that reinfection is not probable and that post-infection immunity is at least temporary and short. Conclusion Based on our review, we concluded that a positive polymerase chain reaction retest could be due to several reasons and should not always be considered as reinfection or reactivation of the disease. Most relevant studies in positive retest patients have shown relative and probably temporary immunity after the reCoVery of the disease.

Reinfection risk of novel coronavirus (COVID-19): A systematic review of current evidence

Can a patient diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) be infected again? This question is still unsolved. We tried to analyze local and literature cases with a positive respiratory swab after recovery. We collected data from symptomatic patients diagnosed with SARS-CoV-2 infection in the Italian Umbria Region that, after recovery, were again positive for SARS-CoV-2 in respiratory tract specimens. Samples were also assessed for infectivity in vitro. A systematic review of similar cases reported in the literature was performed. The study population was composed of 9 patients during a 4-month study period. Among the new positive samples, six were inoculated in Vero-E6 cells and showed no growth and negative molecular test in culture supernatants. All patients were positive for IgG against SARS-CoV-2 nucleoprotein and/or S protein. Conducting a review of the literature, 1350 similar cases have been found. The presumptive reactivation occurred in 34.5 days on average (standard deviation, SD, 18.7 days) after COVID-19 onset, when the 5.6% of patients presented fever and the 27.6% symptoms. The outcome was favorable in 96.7% of patients, while the 1.1% of them were still hospitalized at the time of data collection and the 2.1% died. Several hypotheses have been formulated to explain new positive respiratory samples after confirmed negativity. According to this study, the phenomenon seems to be due to the prolonged detection of SARS-CoV-2 RNA traces in respiratory samples of recovered patients. The failure of the virus to replicate in vitro suggests its inability to replicate in vivo.

/pdf/is-recurrence-possible-in-coronavirus-disease-2019-covid-19-ym9sl61mq9.pdf

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations. Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software. Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00-84.72) vs. 58.33% (52.78-68.06) in scope and purpose, 59.72% (38.89-75.00) vs. 36.11% (33.33-36.11) in stakeholder involvement, 64.58% (32.29-71.88) vs. 22.92% (16.67-26.56) in rigor of development, 75.00% (52.78-86.81) vs. 52.78% (50.00-63.89) in clarity of presentation, 40.63% (22.40-62.50) vs. 20.83% (13.54-25.00) in applicability, and 58.33% (50.00-100.00) vs. 50.00% (50.00-77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P < 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/- azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued. Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/- azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.

/pdf/quality-of-and-recommendations-for-relevant-clinical-20bkctf2lq.pdf

Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal

The number of children with confirmed coronavirus disease 2019 (COVID-19) is increasing substantially due to the lack of special prevention and control measures, especially in younger age groups.1 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus. No specific therapies have been shown effective to date.2 Treatment is mainly directed at symptomatic relief and includes antipyretics, antitussives, mucolytics, and anti-diarrheal therapy. If the disease does not resolve, then antiviral and antibiotic therapy may be used. According to the guidelines for treatment of SARS-CoV-2 infection (Trial Version 7),3 patients can be discharged if they meet all the criteria for clinical cure. A small proportion of adults experience recurrence in a positive test for SARS-CoV-2 during convalescence,4-6 but there are currently no known specific clinical characteristics to predict the reactivation of SARS-CoV-2.6 To the best of our knowledge, there are no published studies on the reactivation of SARS-CoV-2 in children. The aim of this study was to determine the clinical features of children with SARS-CoV-2 reactivation after hospital discharge.

https://journals.sagepub.com/doi/pdf/10.1177/0009922820928057

Characteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge.

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Characteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge.