The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe 4 adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.

COVID 19 is associated with pulmonary cavitation as rare late complication . Cavitatory lesion in COVID 19 recovered patient is very rare and can cause significant morbidity and mortality. we present case series associated with pulmonary cavitation as late complication.

Fluvoxamine for COVID-19 ICU patients?Vladimir TrkuljaDepartment of PharmacologyZagreb University School of MedicineŠalata 11, Zagreb, Croativladimir.trkulja@mef.hrNumber of words: 800Number of figures/tables: 1To the Editor,I read with interest a recently BJCP-accepted manuscript on the use of fluvoxamine in COVID-19 patients who needed admission to an intensive care unit (ICU) 1. It was instructive to read about the pre-existing clinical experience and about possible mechanisms of presumed benefits of fluvoxamine in COVID-19. However, attention needs to be drawn to the suggested effect of fluvoxamine quantified as a 40% reduction in instantaneous risk of death. The authors report1 on a cohort (n=51) of patients who, upon ICU admission, were treated with oral fluvoxamine added to the standard of care (SoC) (3x100 mg/day over 15 days, then 2x50 mg/day over 7 days), and who were compared to a cohort (n=51) of SoC-only patients. The two cohorts were said to be matched 1. Based on reported data 1, it appears that the patients were matched exactly in respect to gender and COVID-19 vaccination status, and, seemingly, on a rather narrow age-caliper, but the matching method was not reported 1; not reported was also a measure of matching adequacy – standardized difference (d ), a preferred method of balance assessment (adequate if d <0.1) since independent of the sample size 2. Based on the reported data1, for example, the fluvoxamine – SoC d regarding body mass index was -0.30 (-0.31 in women and -0.29 in men); also, d=-0.122 regarding history of diabetes,d= -0.350 regarding history of treated hypertension,d=-0.11 regarding on-admission APACHE score – all suggesting a considerable imbalance between the two cohorts (lower values in the fluvoxamine cohort). The authors provide Kaplan-Meier curves of time-to-death (or ICU discharge) but without the numbers at risk1. Still, data could be read from the graphs and curves reconstructed (Figure 1A):(i) the first marked difference between the treated and controls occurs during the first 7 days of observation – 3 patients died and 3 were censored in the former, and 11 died and 4 were censored the latter cohort (Figure 1A). This difference in deaths (3 vs. 11) did not change over the entire later period since the overall difference in the number of deaths was 9 (30/51 in treated vs. 39/51 in controls). This would indicate a very rapid-onset (and subsequently “lost”) effect of fluvoxamine, which does not seem pharmacologically plausible. The assumed fluvoxamine mechanisms1 are not of the immediate-onset type; with a 3x100 mg/day dosing, elimination half-life is likely to extend well beyond 30 hours, hence steady-state would be achieved only after 7-10 days 3. Combined with the baseline imbalance between groups, this indicates that the initial separation of the two curves – more or less preserved throughout the entire subsequent period - was likely not attributable to fluvoxamine; (ii) after day 21, and particularly after day 28, the numbers at risk were very low, and after day 35 there were no further events (Figure 1A), hence accounting for the entire curve is likely misleading 4; (iii) although the curves do not cross (Figure 1A), they indicate a possibility that hazard ratio varied over time. Hazard ratio as generated in a Cox proportional hazard model (as done by the authors) is an average of values that can change over time5; it is also inherently prone to selection bias and, even in absence of confounding its interpretation is not straightforward5. This holds for randomized and particularly for non-randomized settings 5. Reconstructed data depicted in Figure 1A were used to fit a complementary log-log model for continuous time process taking into account the first 35 days (no events after that point): the method treats time as a continuous but more “coarsely” measured variable, in intervals of identical length (in this case 7-day intervals, i.e., weeks); based on assumption of constant hazard within the interval, the method provides period-specific (for weeks 1-5) hazard ratios 6, which is likely a preferable option 5. Figure 1B depicts estimated probabilities of death and HRs: it is only during week 1 that the hazard appeared lower in treated – a period during which, as elaborated, fluvoxamine most likely had no effect. Finally, authors fitted a multivariable Cox model 1to substantiate the fluvoxamine effect. With a total of 15 independents in a study with 102 subjects, the model was likely overfitted and susceptible to bias arising from over(unnecessary)-adjustments 7. But more importantly, it included adjustment for renal replacement therapy (RRT), which was actually one of the outcomes. Inadequacy of adjustments for post-exposure outcomes as if they were baseline covariates has been extensively elaborated 8 and almost inevitably results in a considerable bias, regardless of whether the respective variable was actually a mediator or a collider 8. Such adjustments require implementation of marginal structural models or some of the g-estimation methods 9.Overall, the reported difference between the two cohorts of patients is more likely bias arising from design and analysis than evidence supporting a causal effect of fluvoxamine.ReferencesČalušić M, Marčec R, Lukša L et al. Safety and efficacy of fluvoxamine in COVID-19 ICU patients: an open label, prospective cohort trial with matched controls. Br J Clin Pharmacol . 2021; doi: 10.1111/bcp.15126.Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci . 2010; 25(1):1-21.Hiemke C, Hartter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther . 2000; 85 (1):11-28.Machin D, Cheung YB, Parmar MKB, eds. Survival analysis: a practical approach . 2nd ed. Chichester, West Sussex: John Wiley & Sons Ltd; 2006. p.38.Hernan MA. The hazards of hazard ratios. Epidemiology 2010; 21(1):13-15.Prentice RL, Gloecker LA. Regression analysis of grouped survival data with application to breast cancer data. Biometrics 1978; 34(1):57-67.Schisterman EF, Core SF, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiological studies. Epidemiology 2009; 20(4):488-495.Greenland S. Quantifying biases in causal models: classical confounding vs collider-stratification bias. Epidemiology 2003; 14(4):300-306.Hernan MA, Robins JM, eds. Causal inference: What if . 1st ed. CRC Press LLC; 2019.Figure 1 . Summary of re-analysis of survival data published in ref. 1. A . Reconstructed curves of Kaplan-Meier product-limit estimates. Data1 were read using a digitizing software, and were re-analyzed and curves were drawn using JMP 13 software (SAS Institute Inc., Cary, NC). Upward oriented ticks indicate censorings, downward oriented ticks indicate failures. ICU – intensive care unit. B . Estimated probabilities of death during weeks 1 to 5 by treatment (Fluvox – fluvoxamine) and period-specific hazard ratios (HR) with confidence intervals. A complementary log-log model was fitted to reconstituted data using SAS 9.4 for Windows (SAS Inc., Cary, NC).

Objective: Evaluate the impact of the timing of SARS-CoV-2 infection on pregnancy outcomes in a low-middle income setting. Design: two parallel, observational studies. Setting and population: pregnant women or women presenting for labour, enrolled between April-September 2020, in South Africa. Methods: i) longitudinal follow-up study of symptomatic or asymptomatic pregnant women investigated for SARS-CoV-2 infection antenatally, ii) cross-sectional study of SARS-CoV-2 infection at time of labour. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT). Main Outcome Measures: association of SARS-CoV-2 infection on nasal swab and birth outcomes. Results: Antenatally, 793 women were tested for SARS-CoV-2. Overall SARS-CoV-2 infection was confirmed in 138 women, including 119/275 with symptomatic illness (COVID-19) and 19/518 asymptomatic women; 493 women were asymptomatic and SARS-CoV-2 non-reactive. Women with COVID-19 were 1.66-times (95%CI: 1.02, 1.71) more likely to have a low-birthweight newborn (30%) compared to asymptomatic women without SARS-CoV-2 (21%). Overall, 3117 women were tested for SARS-CoV-2 infection at delivery, including 1560 healthy women with an uncomplicated term delivery. Adverse birth outcomes or pregnancy-related complications were not associated with infection at delivery. Among women with SARS-CoV-2 infection at delivery, NAAT was reactive on 6/98 of maternal blood samples, 8/93 of cord-blood, 14/54 of placentas and 3/22 of nasopharyngeal swabs from newborns collected within 72-hours of birth. Conclusions: Antenatal, but not intrapartum, SARS-CoV-2 infection was associated with low-birthweight delivery. Maternal infection at the time of labour was associated with in utero foetal and placental infection, and possible vertical and/or horizontal viral transfer to the newborn.

Children with sickle cell disease (SCD) are at increased risk for severe illness due to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). We describe the successful native lung recovery of a child with SCD referred for lung transplant (LTx) evaluation who was on prolonged veno-venous extracorporeal membrane oxygenation (VV-ECMO). He initially presented with acute chest syndrome complicated by SARS-CoV-2 infection that ultimately required dual-lumen, single bicaval VV-ECMO cannulation for respiratory support. Despite increased risk of hemolysis and thrombosis from SCD and SARS-CoV-2 infection, he was successfully supported on VV-ECMO for 71 days without complications leading to native lung recovery with meticulous management of his SCD therapy. This report provides new insight on our approach to VV-ECMO support in a child with SCD and SARS-CoV-2 infection. With a successful outcome, the patient has returned home but still on mechanical ventilation with LTx still an option if he is not eventually liberated from invasive respiratory support.

The evaluation of the lung by ultrasound is an adjunct tool to the clinical assessment. Among different hallmarks at lung ultrasound, B-lines are well known artifacts which are not correlated to identifiable structures but can be used as an instrument for pathological classification. Multiple B-lines are the sonographic sign of lung interstitial syndrome with a direct correlation between the number of B-lines and the severity of the interstitial involvement of lung disease. In neonatology and paediatrics, the quantitative assessment of B-lines is questionable as opposed to in adult medical care. Counting B-lines is an attempt to enrich the clinical assessment and clinical information, and not simply arrive at a dichotomous answer. A semiquantitative or quantitative B-lines assessment was shown to correlate with fluid overload and demonstrated prognostic implications in specific neonatal and paediatric conditions. In neonatology, the count of B-lines is used to predict the need for admission in neonatal intensive care unit and the need for exogenous surfactant treatment. In paediatrics, the B-lines count has the role of quantifying hypervolemia in infants and children receiving dialysis. B-lines as predictors of length of stay in the paediatric intensive care unit after cardiac surgery, as a marker of disease severity in bronchiolitis, or as an indicator of lung involvement from SARS-CoV-2 infection are speculative and not yet supported by solid evidence. Lung ultrasound with the quantitative B-lines assessment is promising. The current evidence allows to use the quantification of B-lines in a limited number of neonatal and paediatric diseases.

In the COVID-19 pandemic, the overlap of clinical features between the other viral infections, make a reliable diagnosis difficult in the initial stage of illness. We describe the first confirmed case of CCHF in Tehran province during this year, who first misdiagnosed as COVID-19 infection.

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma), seems more susceptible to serious illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline, right heart thickning in animal prophylactic. The current study reviewed existing data that the PDE-4 inhibitor protects not just renal tissues but also other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related with a decrease in oxidative and inflammatory burden, caspase-3 suppression, and increased PKA/cAMP levels in renal and other organ tissue.

Background: In response to the coronavirus disease (COVID-19) outbreak that unfolded across Europe in 2020, the World Health Organisation called for repurposing existing influenza surveillance systems to monitor COVID-19. This analysis aimed to compare descriptively the extent to which influenza surveillance systems were adapted and enhanced, and how COVID-19 surveillance could ultimately benefit or disrupt routine influenza surveillance. Methods: We used a previously developed framework in France, Germany, Italy, Spain and the United Kingdom to describe COVID-19 surveillance and its impact on influenza surveillance. The framework divides surveillance systems into 7 sub-systems and 20 comparable outcomes of interest, and uses 5 evaluation criteria based on WHO guidance. Information on influenza and COVID-19 surveillance systems were collected from publicly available resources shared by European and national public health agencies. Results: Overall, non-medically attended, virological, primary care and mortality surveillance were adapted in most countries to monitor COVID-19, whilst community, outbreak, and hospital surveillance were reinforced in all countries. Data granularity improved, with more detailed demographic and medical information recorded. A shift to systematic notification for cases and deaths enhanced both geographic and population representativeness whilst the sampling strategy benefited from the roll out of widespread molecular testing. Data communication was greatly enhanced, contributing to improved public awareness. Conclusions: Well-established influenza surveillance systems are a key component of pandemic preparedness and their upgrade allowed European countries to respond to the COVID-19 pandemic. However, uncertainties remain on how both influenza and COVID-19 surveillance can be jointly and durably implemented.

Abstract Development of serious complications after COVID-19 infection can occur even in very young patients without any comorbidities. Appropriate, non-aggressive ventilation and adequate treatment is essential for COVID-19 convalescents and may prevent them from aggravating surgical procedures.

Supraclavicular Lymphadenopathy after COVID-19 vaccinationKelsey Larkin 1, Archana Sharma DO2, Richard Drachtman MD,2, Gratian Salaru , MD31 Robert Wood Johnson Medical School2Division of Pediatric Hematology, Rutgers Cancer Institute, Robert Wood Johnson Medical School3Department of Pathology, Robert Wood Johnson Medical SchoolCorrespondence to Archana Sharma, DO, Rutgers Cancer Institute of NJ, 195 Little Albany Street, Room 3507, New Brunswick, NJ 08901.Telephone: 732-235-8864Sharmaar@cinj.rutgers.eduText Word Count: 974Brief running title: Lymphadenopathy after COVID-19 vaccination.Key words: lymphadenopathy, COVID-19, vaccine,Images: 2

Liberal use of oxygen plays a significant role in exacerbating the long-term lung injuries associated in COVID-19. Hypoxemia and hypoxia are two different entities. Correcting hypoxemia without hypoxia tends to have disastrous effect and delays lung healing.

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. Our aim was to describe clinical findings and outcomes of SARS-CoV-2 viral infection and Covid-19 disease cared for at a large pediatric tertiary care hospital during the first year of the pandemic. Methods: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 between March 2020 and April 2021 were included. The files of patients diagnosed with covid-19 were reviewed retrospectively. Results: 467 children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups (p<0.05). Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/467). Conclusion: While SARS-CoV-2 infection may be asymptomatic and Covid-19 disease usually has a mild clinical course, some children have severe disease or mortality.

Primary ciliary dyskinesis (PCD) is an autosomal recessive disorder associated with impaired mucociliary clearance caused by defects in ciliary structure and function. The major clinical feature of PCD is recurring or persistent respiratory tract infection. Respiratory tract colonization with drug-resistant organisms impact the frequency of infections and lung function decline. Protective gear has been employed by caregivers in an attempt to control respiratory tract bacterial spread between patients with cystic fibrosis but use in PCD is not known. We conducted a web-based survey to investigate infection control and prevention practices of PCD centers in North America. The response rate was 87.0%. Prior to the COVID-19 pandemic, glove, gown and mask use was variable, and only 3.7% of centers used masks during encounters with PCD outpatients. After COVID-19 mandates are lifted, 48.1% of centers plan to continue to use masks during outpatient care, while the practice regarding use of gloves and gowns was not influenced by the current pandemic. There is no uniform practice for infection control in PCD care indicating the need for practice guidelines. Mitigation of respiratory virus transmission learned during the COVID-19 pandemic may impact future infection control approaches used for patients with PCD and other lung diseases.

Pulmonary infections represent the major causes of morbidity and mortality in cystic fibrosis(CF). Here, we report a3-month old infant with pancreatic insufficient CF was hospitalized with positive RT-PCRtest for COVID-19. He was treated successfully. Hypertonic saline can be hypothesized as a treatment regimen against COVID-19 infection after further investigation

A 16-year-old female presented to our ED with fever and coughing of blood for 3 days. She is known to have SLE for 5 months and takes oral prednisone. She was tested positive for COVID19. She developed hypocalcemia with clinically-diagnosed massive pulmonary embolism. She was treated with heparin and recovered.

Cutaneous manifestations are increasingly reported in patients with COVID-19 disease .A review of cutaneous manifestations of COVID-19 especially among health care workers (HCW) is thus required.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare disease characterized by recurrent severe itching and jaundice. Coronavirus disease 2019 (COVID-19) is a multisystemic acute viral disease and the liver is frequently affected. Here, we wanted to present a BRIC case triggered by COVID-19 infection, discussing it together with current information.

Patients and their families are discouraged from the restrictions on hospital visits for coronavirus Infection control. This separation might further deteriorate the mental health of both vulnerable patients and their family members. Home care could be a preferable solution to this problem.

Ectopia cordis (EC) is a rare congenital condition characterized by a partial or complete defect of the anterior chest wall. It is associated with ventricular and atrial septal defects (ASD),. This study aimed to explore the cardiac manifestations of EC complicated by coronavirus disease 2019 (COVID-19).

Spontaneous bilateral intracerebral hemorrhage is an outstandingly infrequent context. Ensuing hypertension, trauma inflicted to the brain case is another common cause that out turn into the sequelae of bilateral intracerebral hemorrhage. Lately, a few cases of bilateral basal ganglia bleed have been revealed, as a repercussion of COVID-19 infection.

Deferring non-emergent cardiac surgery became the strategy of choice for several international healthcare systems afflicted by high case burdens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) in order to both conserve valuable healthcare resources and protect patients from possible exposure. Missing from the available dataset to help guide policy development has been a clear understanding of the extent to which COVID-19 infection modulates cardiac surgery outcomes. In their investigation, Bonalumi and colleagues uncovered an inpatient COVID-19 positivity rate of almost 10 times higher than that of the general Italian population, as well as a mortality rate over 20 times higher amongst cardiac surgery patients with perioperative COVID-19 infection compared to those COVID-negative. While the summation of available evidence points to the serious consideration cardiac surgeons must give to delaying surgeries during the COVID-19 pandemic, recognition must be given to the risks that postponing cardiac surgery may have on patient outcomes. Emerging data is beginning to demonstrate the efficacy of vaccination in preventing postoperative COVID-19 infection and morbidity.

Stringent public health measures imposed across Canada to control the COVID-19 pandemic have nearly suppressed most seasonal respiratory viruses, with the notable exception of human rhinovirus/enterovirus (hRV/EV). Thanks to this unexpected persistence, we highlight that hRV/EV could serve as a sentinel for levels of contact rate in populations to inform on the efficiency¬, or the need of, public health measures to control the subsequent COVID-19 epidemic, but also for future epidemics from other seasonal or emerging respiratory pathogens.

Psychological and psychosocial issues are more prominent issues of an individual in any disease, which could further deteriorate patients’ condition and hamper their quality of life. However, in treating SARS-CoV-2/COVID-19, those patients’ mental, social, and emotional aspects are still overlooked.