Mese: Giugno 2020

Del Barba P, Canarutto D, Sala E, et al. COVID-19 cardiac involvement in a 38-day old infant .Pediatr Pulmonol. 2020;10.1002/ppul.24895.

The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS-CoV-2 in children should always be taken into account.

Zhang L, Tao Y, Wang J, et al. Early characteristics of the COVID-19 outbreak predict the subsequent epidemic size . Int J Infect Dis. 2020;S1201-9712(20)30429-X

Objectives: The largely resolved first wave of the COVID-19 epidemic in China provides a unique opportunity to investigate how the early characteristics of the COVID-19 outbreak predicts its subsequent size.

Methods: We collected publicly available COVID-19 epidemiological data from 436 Chinese cities during 16th January-15th March 2020. Based on 45 cities which reported >100 confirmed cases, we examined the correlation between early-stage epidemic characteristics and subsequent epidemic size.

Results: We identified a transition point from a slow- to a fast-growing phase for COVID-19 at 5.5 (95% CI, 4.6-6.4) days after the first report, and 30 confirmed cases marked a critical threshold for this transition. The average time for the number of confirmed cases to increase from 30 to 100 (time from 30-to-100) was 6.6 (5.3-7.9) days, and the average case-fatality rate in the first 100 confirmed cases (CFR-100) was 0.8% (0.2-1.4%). The subsequent epidemic size per million population was significantly associated with both of these indicators. We predict a ranking of epidemic size in the cities based on these two indicators and found it highly correlated with the actual ranking of epidemic size.

Conclusions: Early epidemic characteristics are important indicators for the size of the entire epidemic.

Sajadi MM, Habibzadeh P, Vintzileos A, Shokouhi S, Miralles-Wilhelm F, Amoroso A. Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19). JAMA Netw Open. 2020;3(6):e2011834

Importance: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies.

Objective: To examine the association of climate with the spread of COVID-19 infection.

Design, setting, and participants: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020.

Main outcomes and measures: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis.

Results: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m3). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases.

Conclusions and relevance: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

Parasa S, Desai M, Thoguluva Chandrasekar V, et al. Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e2011335.

Importance: Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces.

Objective: To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19.

Data sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included “COVID-19,” “SARS-Cov-2,” and/or “novel coronavirus.”

Study selection: Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms.

Data extraction and synthesis: Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2).

Main outcomes and measures: Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed.

Results: Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2 = 94%), but no statistically significant publication bias noted.

Conclusions and relevance: These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.

Gharpure R, Hunter CM, Schnall AH, et al. Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention – United States, May 2020. MMWR Morb Mortal Wkly Rep. 2020;69(23):705-709

A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.

Fosbøl EL, Butt JH, Østergaard L, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality . JAMA. 2020;10.1001/jama.2020.11301.

Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.

Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.

Design, setting, and participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.

Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date.

Main outcomes and measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.

Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).

Conclusions and relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

Ellinghaus D, Degenhardt F, Bujanda L, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure . N Engl J Med. 2020;10.1056/NEJMoa2020283.

Background: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.

Methods: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.

Results: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5).

Conclusions: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).

Lavizzari A, Klingenberg C, Profit J, et al. International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic. Pediatr Res. 2020;10.1038/s41390-020-0976-5.

Background: The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers.

Methods: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies.

Results: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance.

Conclusions: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus.

Impact: At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

Thi Tran H, Thi Kim Nguyen P, Thi Li H, et al. Appropriate care for neonates born to mothers with COVID-19 disease. Acta Paediatr. 2020;10.1111/apa.15413.

The global COVID-19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, morbidity and mortality in the general population. Evidence-based guidance on caring for babies born to mothers with COVID-19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin-to-skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID-19 and her baby.

Griffin I, Benarba F, Peters C, et al. The Impact of COVID-19 Infection on Labor and Delivery, Newborn Nursery, and Neonatal Intensive Care Unit: Prospective Observational Data from a Single Hospital System. Am J Perinatol. 2020;10.1055/s-0040-1713416.

Objective: Since its emergence in late 2019, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the novel coronavirus that causes novel coronavirus disease 2019 (COVID-19), has spread globally. Within the United States, some of the most affected regions have been New York, and Northern New Jersey. Our objective is to describe the impact of COVID-19 in a large delivery service in Northern New Jersey, including its effects on labor and delivery (L&D), the newborn nursery, and the neonatal intensive care unit (NICU).

Materials and methods: Between April 21, 2020 and May 5, 2020, a total of 78 mothers (3.6% of deliveries) were identified by screening history or examination to either be COVID-19 positive or possible positives (persons under investigation). Of the mothers who were tested after admission to L&D, 28% tested positive for SARS-CoV-2.

Discussion: Isolation between mother and infant was recommended in 62 cases, either because the mother was positive for SARS-CoV-2 or because the test was still pending. Fifty-four families (87%) agreed to isolation and separation. The majority of infants, 51 (94%), were initially isolated on the newborn nursery. Six needed NICU admission. No infants had clinical evidence of symptomatic COVID-19 infection. Fourteen infants whose mothers were positive for SARS-CoV-2, and who had been separated from the mother at birth were tested for SARS-CoV-2 postnatally. All were negative.

Results: COVID-19 posed a significant burden to mothers, infants, and staff over the 5-week study period. The yield from screening mothers for COVID-19 on L&D was high. Most families accepted the need for postnatal isolation and separation of mother and newborn.

Conclusion: Our study suggests that the transmission of SARS-CoV-2 from mother to her fetus/newborn seems to be uncommon if appropriate separation measures are performed at birth.

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