Comparison between Nasopharyngeal and Saliva Samples for the Detection of Respiratory Viruses in Children with Acute Lower Respiratory Tract Infections: A Pilot Study.

PURPOSE: During the COVID-19 pandemic, the use of salivary swabs (SS) to detect the SARS-CoV-2 virus has been implemented and widely studied in adults and children. However, the role of SS in detecting other common respiratory viruses in children is poorly investigated. METHODS: Children younger than 18 years of age admitted with respiratory signs and symptoms underwent both nasopharyngeal and SS procedures. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SS were calculated, considering the nasopharyngeal swab result as the gold standard. RESULTS: A total of 83 patients (44 females, 53%) underwent both nasopharyngeal and SS procedures. Overall, the sensitivity of SS was 49.4%. Sensitivity according to different respiratory viruses ranged from 0% to 71.43%, while the specificity ranged from 96% to 100%. Negative predictive value ranged from 68.06% to 98.8%, while positive predictive value ranged from 0 to 100%. SS sensitivity in patients younger than 12 months of age was 39.47%, while in patients older than or equal to 12 months of age it was 57.78%. Patients with negative SS had a significantly lower median age (8.5 months (15.25) vs. 23 months (34), p = 0.001) and a significantly lower quantity of median saliva collected for salivary analysis (0 µL (213) vs. 300 µL (100), p < 0.001). CONCLUSIONS: SS has a relatively low sensitivity in detecting common respiratory viruses in children with LRTI, with a lower probability in younger children (and in particular those younger than 6 months of age) or those from whom we have collected lesser amounts of saliva. New strategies to improve saliva collection are needed for testing on a larger study population.

Role of Lung Ultrasound in the Follow-Up of Children with Previous SARS-CoV-2 Infection: A Case-Control Assessment of Children with Long COVID or Fully Recovered.

Lung ultrasound (LUS) can detect lower respiratory tract involvement in children with acute SARS-CoV-2 infection. However, its role in follow-up assessments is still unclear. To describe LUS findings in children after SARS-CoV-2 infection, we conducted a prospective study in a population of pediatric patients referred to the post-COVID unit in a tertiary center during the study period from February 2021 to May 2022. Children were classified as recovered from acute infection or with persisting symptoms. LUS was performed in all children and a LUS score (ranging from 0 to 36 points) was calculated according to the Italian Academy of Thoracic Ultrasound. Six hundred forty-seven children (304 females, 47%) were enrolled. The median follow-up evaluation was two months. The median age was 7.9 (IQR: 6) years. At the follow-up evaluation, 251 patients (38.8%) had persistent symptoms, of whom 104 (16.1%) had at least one respiratory symptom. The median LUS level was 2 (IQR: 4). LUS findings and LUS scores did not differ in children with Long COVID compared to the group of children fully recovered from the initial infection. In conclusion, after SARS-CoV-2 infection, LUS was mostly normal or showed minimal artifacts in all groups of children.

Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study.

Background: Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol. Methods: We performed a prospective "disease-based" cohort study between 01/02/2020 to 31/10/2022 including children aged 0-18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher's exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan-Meier method. Findings: 1243 children were included, median age: 7.5 (4-10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18-1.28), comorbidities (OR 1.68; 95% CI 1.14-2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91-12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC. Interpretation: In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed. Funding: This study has been funded by Pfizer non-competitive grant, granted to DB (# 65925795).

Risk Factors for Persistent Anosmia and Dysgeusia in Children with SARS-CoV-2 Infection: A Retrospective Study.

BACKGROUND: Olfactory and gustative dysfunctions are two of the most common post-acute sequelae of SARS-CoV-2 infection in children, which can have a negative impact on the routines of children and families. As several children have had COVID-19 since the Omicron variant, it is important to investigate if this increase in infections is reflected in higher olfactory/taste disfunctions. The primary aim of this study was to characterize the presence of olfactory/gustative problems in a cohort of children, its evolution, and its association with risk factors such as COVID-19 variant, hospitalization, presence of olfactory/gustative dysfunction during the acute phase, and vaccination. METHODS: This was a retrospective analysis of children with microbiologically confirmed SARS-CoV-2 infection evaluated in person at a referral pediatric post-COVID-19 clinic in Rome, Italy. We included children younger than 19 years old, evaluated from the beginning of the pandemic up to October 2022. At specific timepoints, we investigated the presence of olfactory/taste disfunctions and evaluated them according to the SARS-CoV-2 variants circulating at the time of infection. RESULTS: A total of 1250 children (650 females; 52.0%) with a mean age of 6.77 (±4.12) years were included in the study. At 3, 6, 12, and 18 months, 12 (9.6%), 7 (5.6%), 2 (1.6%), and 1 (0.8%) of the children reported anosmia and dysgeusia post-COVID-19 infection, respectively. The presence of anosmia and dysgeusia during the acute phase of infection and being infected with a pre-Omicron variant were found to be significant risk factors for persistent olfactory and gustatory dysfunction during all follow-up periods. CONCLUSIONS: anosmia and dysgeusia symptoms tended to decrease gradually over time, but not all children recovered quickly.

Changes in Childhood Immunizations and Intermittent Preventive Malaria Treatment in a Peripheral, Referral Immunization Center During the First 12 Months of COVID-19 Pandemic in Sierra Leone, Western Africa.

Background: There is increasing evidence that the COVID-19 pandemic disrupted childhood immunization services. However, detailed reports on immunizations and preventive antimalarial prophylactic treatments delivered and how the trends changed in referral centers in low-income countries are still missing. Methods: We performed a retrospective cross-sectional study. Data for vaccinations administered to children <5 years of age, according to the local vaccination schedule, were extracted from the official records of the Kent Community Health Post, Sierra Leone, in the period between April 2019 and March 2021. We compared the vaccinations performed in the first year, considered as a pre-Covid period, with the second year, post-Covid period. Both the period was then divided in four trimester each and the same analysis was operated for each trimester. A Chi-square goodness of fit test was performed to compare the number of vaccinations performed both in the 2 years and in the 8 trimesters. Findings: Seven thousand two hundred and eighty-three vaccinations were administered: 4,641 in the period between April 2019 and March 2020 and 2,642 between April 2020 and March 2021. The drop in immunizations performed began as soon as the first cases were described in China. The drops were statistically significant when the first three trimesters of the two study periods were compared, while no statistically significant differences were observed for all the vaccines performed in the 4th trimesters. Vaccines administered at birth (BCG) were less affected compared to booster vaccinations. Conclusions: Immunizations administered in a referral health center in Sierra Leone significantly declined during the pandemic. Although the decline was less pronounced in the last months of the pandemic, we don't think that the small increase would indicate the recovery of previously missed vaccinations. These findings open new public health challenges for the coming years.

Extended coagulation profile of children with Long Covid: a prospective study.

Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8-12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.

Changes in Childhood Immunizations and Intermittent Preventive Malaria Treatment in a Peripheral, Referral Immunization Center During the First 12 Months of COVID-19 Pandemic in Sierra Leone, Western Africa

Background There is increasing evidence that the COVID-19 pandemic disrupted childhood immunization services. However, detailed reports on immunizations and preventive antimalarial prophylactic treatments delivered and how the trends changed in referral centers in low-income countries are still missing. Methods We performed a retrospective cross-sectional study. Data for vaccinations administered to children <5 years of age, according to the local vaccination schedule, were extracted from the official records of the Kent Community Health Post, Sierra Leone, in the period between April 2019 and March 2021. We compared the vaccinations performed in the first year, considered as a pre-Covid period, with the second year, post-Covid period. Both the period was then divided in four trimester each and the same analysis was operated for each trimester. A Chi-square goodness of fit test was performed to compare the number of vaccinations performed both in the 2 years and in the 8 trimesters. Findings Seven thousand two hundred and eighty-three vaccinations were administered: 4,641 in the period between April 2019 and March 2020 and 2,642 between April 2020 and March 2021. The drop in immunizations performed began as soon as the first cases were described in China. The drops were statistically significant when the first three trimesters of the two study periods were compared, while no statistically significant differences were observed for all the vaccines performed in the 4th trimesters. Vaccines administered at birth (BCG) were less affected compared to booster vaccinations. Conclusions Immunizations administered in a referral health center in Sierra Leone significantly declined during the pandemic. Although the decline was less pronounced in the last months of the pandemic, we don't think that the small increase would indicate the recovery of previously missed vaccinations. These findings open new public health challenges for the coming years.

Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study.

Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62-10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19.