Update of European Society of Clinical Microbiology and Infectious Diseases coronavirus disease 2019 guidelines: diagnostic testing for severe acute respiratory syndrome coronavirus 2.

SCOPE: Since the onset of COVID-19, several assays have been deployed for the diagnosis of SARS-CoV-2. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first set of guidelines on SARS-CoV-2 in vitro diagnosis in February 2022. Because the COVID-19 landscape is rapidly evolving, the relevant ESCMID guidelines panel releases an update of the previously published recommendations on diagnostic testing for SARS-CoV-2. This update aims to delineate the best diagnostic approach for SARS-CoV-2 in different populations based on current evidence. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. The panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the population, intervention, comparison, and outcome (PICO) format was developed at the beginning of the process. For each PICO, 2 panel members performed a literature search focusing on systematic reviews with a third panellist involved in case of inconsistent results. The panel reassessed the PICOs previously defined as priority in the first set of guidelines and decided to address 49 PICO questions, because 6 of them were discarded as outdated/non-clinically relevant. The 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)-adoption, adaptation, and de novo development of recommendations (ADOLOPMENT)' evidence-to-decision framework was used to produce the guidelines. QUESTIONS ADDRESSED BY THE GUIDELINES AND RECOMMENDATIONS: After literature search, we updated 16 PICO questions; these PICOs address the use of antigen-based assays among symptomatic and asymptomatic patients with different ages, COVID-19 severity status or risk for severe COVID-19, time since the onset of symptoms/contact with an infectious case, and finally, types of biomaterials used.

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis.

BACKGROUND: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. OBJECTIVES: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. DATA SOURCES: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. STUDY ELIGIBILITY CRITERIA: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. PARTICIPANTS: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. TEST/S: Molecular and/or antigen-based SARS-CoV-2 POCTs. REFERENCE STANDARD: Laboratory-based SARS-CoV-2 RT-PCR. ASSESSMENT OF RISK OF BIAS: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. METHODS OF DATA SYNTHESIS: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. RESULTS: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9-95.4%) and 97.6% (95% CI, 96.6-98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2-73.8%) and 98.9% (95% CI, 98.5-99.2%), respectively. DISCUSSION: Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.

Immunogenicity 6 months post COVID-19 mRNA-vaccination among adolescents with juvenile idiopathic arthritis on treatment with TNF-inhibitors.

OBJECTIVES: Mass vaccination is the most effective strategy for controlling the COVID-19 pandemic. This study aimed to evaluate the 6-month immunogenicity after BNT162b2-COVID-19 vaccination in adolescents with JIA on TNFi treatment. METHODS: This single-center study included adolescents with JIA treated with TNFi for at least 18 months. Patients received two doses of COVID-19 vaccine (Pfizer-BioNTech) from April 15th to May 15th 2021. Quantitative measurement of IgG antibodies to SARS-CoV-2-spike-protein-1 was performed at 1,3 and 6 months post-vaccination. RESULTS: Overall, 21 adolescents with JIA in clinical remission at the time of vaccinations were enrolled. None of them discontinued TNFi/MTX treatment at the time of vaccine administration or during the follow-up period. All patients developed a sustained humoral response against SARS-CoV-2 at 1 and 3 months after vaccination (p< 0.05). The antibody levels decreased significantly at 6 months post-vaccination (p< 0.01). The type of JIA did not reveal any differences in the humoral response at 3 (p= 0.894) or 6 months post-vaccination (p= 0.72). No difference was detected upon comparison of the immunogenicity between the different treatment arms (adalimumab vs etanercept) at 3 (p= 0.387) and 6 months (p= 0.526), or TNFi monotherapy vs combined therapy (TNFi plus methotrexate) at 3 (p= 0.623) and 6 months (p= 0.885). CONCLUSIONS: Although mRNA vaccines develop satisfactory immunogenicity at 1- and 3-months post-vaccination in adolescents with JIA on TNFi, SARS-CoV-2 antibody titers decrease significantly overtime, remaining at lower levels at 6 months. Further collaborative studies are required to determine long-term immunogenicity, real duration of immune protection and the need for a booster vaccine dose.

Seroprevalence of anti-SARS-CoV-2 antibodies among children and their parents in Greece.

School closures were enforced as measures to restrain the COVID-19 pandemic, based on the assumption that young children may play a key role in SARS-CoV-2 spread. This study aims to determine the prevalence of SARS-CoV-2 IgG antibodies in children and corresponding parents, in order to improve surveillance and estimate the prevalence of asymptomatic or subclinical COVID-19 cases. A prospective multicenter study was conducted between March and June 2021 in Greece. Children admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 and their parents were tested for anti-Spike SARS-CoV-2 IgG in serum. A questionnaire about clinical and demographic data was completed. The study included 823 participants: 427 children and 396 corresponding parents. The overall seroprevalence was 16.4% in parents and 13.8% in children. Among families with ≥ 1 seropositive child or parent, the combination of a seropositive parent and a corresponding seronegative child was 29.6%, a seronegative parent and a corresponding seropositive child was 24.7%, and a seropositive child with a corresponding seropositive parent was 45.7%. Age, level of education, and school or work attendance were not significantly associated with increased seropositivity. On the contrary, ethnic minority of Roma, close contact with known COVID-19 case, previous symptoms consistent with COVID-19, and mass gatherings were risk factors for seropositivity. CONCLUSION: The spread of SARS-CoV-2 during a period of lockdown in Greece was low in children and comparable to adults most likely due to intrafamilial transmission. Accordingly, it is unlikely that children have boosted virus transmission. WHAT IS KNOWN: • In the earliest months of the pandemic, it was demonstrated that children had significantly lower seroprevalence rates than the older age groups, due to the fact that children had decreased exposure to the virus, because of early public health interventions, such as school and day care closure. • Later, further studies reported that children have similar incidence rate of SARS-CoV-2 infection compared to adults in households and community settings. WHAT IS NEW: • In this seroprevalence study, the spread of SARS-CoV-2 infection during a period of lockdown in Greece with the predominance of the Alpha-variant was particularly low in children and comparable to adults, most likely due to intrafamilial transmission. • These study findings will be useful for decisions regarding non-pharmaceutical interventions during the pandemic, and especially, to guide in designing and implementing appropriate containment measures for schools and social gatherings.

The Psychological Impact of COVID-19 Admission on Families: Results from a Nationwide Sample in Greece.

The aim of the present study was to assess the psychological impact of hospitalization during the COVID-19 pandemic on parents and their offspring. We performed a nationwide cross-sectional study in Greece based on an Internet questionnaire survey. A convenience sample of parents whose offspring had been hospitalized due to COVID-19 (including multisystem inflammatory syndrome in children, MIS-C), diagnosed with COVID-19 but not hospitalized, and hospitalized for another reason during the pandemic were enrolled. Parental stress was assessed using the Perceived Stress Scale (PSS) and the Revised Impact of Event Scale (IES-R) tools, and childhood mental wellbeing with the Children's Revised Impact of Event 13 (CRIES-13) scale. Out of 214 received responses, stress levels were significantly higher in parents whose children had been admitted for COVID-19 or MIS-C versus those not admitted or admitted for other reasons (p < 0.001, for PSS/IES-R). Parental and childhood stress levels were correlated. In the multivariable linear regression analysis, children's hospitalization because of COVID-19 or MIS-C, younger parental age, the existence of comorbidities, and another family member's hospitalization because of COVID-19 were independent factors for higher stress. In light of the above, stricter hospital admission criteria for COVID-19 could be implemented, and psychological support for eventually admitted families may be beneficial.

Transmission of Infections during Cardiopulmonary Resuscitation.

Cardiopulmonary resuscitation (CPR) is an emergency lifesaving endeavor, performed in either the hospital or outpatient settings, that significantly improves outcomes and survival rates when performed in a timely fashion. As with any other medical procedure, CPR can bear potential risks not only for the patient but also for the rescuer. Among those risks, transmission of an infectious agent has been one of the most compelling triggers of reluctance to perform CPR among providers. The concern for transmission of an infection from the resuscitated subject may impede prompt initiation and implementation of CPR, compromising survival rates and neurological outcomes of the patients. Infections during CPR can be potentially acquired through airborne, droplet, contact, or hematogenous transmission. However, only a few cases of infection transmission have been actually reported globally. In this review, we present the available epidemiological findings on transmission of different pathogens during CPR and data on reluctance of health care workers to perform CPR. We also outline the levels of personal protective equipment and other protective measures according to potential infectious hazards that providers are potentially exposed to during CPR and summarize current guidelines on protection of CPR providers from international societies and stakeholders.

Favorable Outcome in Infants Hospitalized With COVID-19: Single Center Experience from Athens, Greece.

This study aims to describe the clinical characteristics and outcome of 92 infants (aged <12 months) with community-acquired coronavirus disease 2019 (COVID-19) between March, 2020 and June, 2021 at a single center in Athens. Infants with COVID-19 developed mild disease (89, 96.7%), and were infected mostly by their household contacts (74, 80.4%). Disease complications were rare, indicating that hospitalization is the result of low threshold for admission rather than disease severity.

Effects of low molecular weight heparin and fondaparinux on mortality, hemorrhagic and thrombotic complications in COVID-19 patients.

Background: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19. Objective: We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases. Design: We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. Data Sources and Methods: MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19-3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses. Conclusion: The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies. Registration: The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

ESCMID COVID-19 guidelines: diagnostic testing for SARS-CoV-2.

SCOPE: The objective of these guidelines is to identify the most appropriate diagnostic test and/or diagnostic approach for SARS-CoV-2. The recommendations are intended to provide guidance to clinicians, clinical microbiologists, other health care personnel, and decision makers. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search focusing on systematic reviews, with a third panellist involved in case of inconsistent results. Quality of evidence assessment was based on the GRADE-ADOLOPMENT (Grading of Recommendations Assessment, Development and Evaluation - adoption, adaptation, and de novo development of recommendations) approach. RECOMMENDATIONS: A total of 43 PICO questions were selected that involve the following types of populations: (a) patients with signs and symptoms of COVID-19; (b) travellers, healthcare workers, and other individuals at risk for exposure to SARS-CoV-2; (c) asymptomatic individuals, and (d) close contacts of patients infected with SARS-CoV-2. The type of diagnostic test (commercial rapid nucleic acid amplification tests and rapid antigen detection), biomaterial, time since onset of symptoms/contact with an infectious case, age, disease severity, and risk of developing severe disease are also taken into consideration.

Serious complications of COVID-19 vaccines: A mini-review.

Τhe most promising approach of fighting COVID-19 and restraining the course of this pandemic is indisputably the universal vaccination of the population with safe and effective vaccines. However, besides the common and usually mild side effects of the authorized vaccines, some rare, major adverse reactions are increasingly being reported worldwide during the post marketing surveillance phase of vaccines' circulation, such as anaphylaxis, vaccine-induced thrombotic thrombocytopenia, myopericarditis and Guillain-Barré syndrome. Despite rare cases with complications from COVID-19 vaccines, the net benefit-risk ratio shows a clearly favorable balance towards COVID-19 vaccination for all age and sex groups. Vaccine adverse events should be identified early and monitored closely. As many aspects of these adverse effects remain still obscure for the medical community and the relevant stakeholders, it is also highly important to be promptly reported. Nonetheless, these complications should not constitute a reason to change the vaccine policy and further studies are needed to alleviate concerns and reluctance to COVID-19 vaccinations.

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.

Real-life evaluation of a COVID-19 rapid antigen detection test in hospitalized children.

Rapid antigen detection (RAD) tests for the detection of SARS-CoV-2 are simpler, faster, and less expensive than the reverse-transcription polymerase chain reaction (RT-PCR) that is currently considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19). The objective of this study was to determine the performance of the PANBIO COVID-19 Ag RAD (Abbott) test, a lateral flow immunoassay that detects the nucleocapsid protein, using as a reference RT-PCR method the Cobas®8800 System (Roche Diagnostics). This prospective study was conducted in a tertiary Children's Hospital and included individuals aged ≤16 years with COVID-19-related symptoms or epidemiological criteria for COVID-19. Two nasopharyngeal samples were collected to perform the PANBIO RAD test and RT-PCR. Of 744 children included, 51 (6.86%) had a positive RT-PCR result. The RAD test detected 42 of 51 PCR-positive children while there were no false-positive results. The overall sensitivity and specificity were 82.35% (95% CI, 71.9%-92.8%) and 100%, respectively. Sensitivity was >95% in symptomatic children. The assay performed poorly in asymptomatically infected children. In agreement with previous studies in adults, the PANBIO RAD test can be useful in screening for COVID-19 in children admitted with symptoms suggestive of the disease, especially in the first days of the illness.

Pericarditis as the Main Clinical Manifestation of COVID-19 in Adolescents.

Children and adolescents with severe acute respiratory syndrome coronavirus 2 infection usually have a milder illness, lower mortality rates and may manifest different clinical entities compared with adults. Acute effusive pericarditis is a rare clinical manifestation in patients with COVID-19, especially among those without concurrent pulmonary disease or myocardial injury. We present 2 cases of acute pericarditis, in the absence of initial respiratory or other symptoms, in adolescents with COVID-19.

Breastfeeding during the novel coronavirus (COVID-19) pandemic: guidelines and challenges.

COVID-19 pandemic has raised questions on pregnant women and newborns' management. Guidelines, issued by most international agencies and national bodies, recommend rooming-in and direct breastfeeding. In the early days of this pandemic, breastfeeding practices have been challenged by fear among both parents and healthcare workers occasionally resulting in mother-newborn separation. We herein review current breastfeeding guidelines and discuss remaining questions and challenges. As we are facing the second wave of this pandemic, more information is gathered, especially regarding possible virus transmissibility through breastfeeding, enabling more definite instructions about breastfeeding practices.

Asian-Pacific perspective on the psychological well-being of healthcare workers during the evolution of the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers. AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes. METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country. RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries. CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.