Mese: Dicembre 2020

van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Crit Care. 2020 Dec 14;24(1):696. doi: 10.1186/s13054-020-03400-9. PMID: 33317589; PMCID: PMC7735177.

Background: In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed.

Objectives: The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19.

Methods: A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections.

Results: Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57-0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present.

Conclusions: Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.

Shah S, Majmudar K, Stein A, Gupta N, Suppes S, Karamanis M, Capannari J, Sethi S, Patte C. Novel Use of Home Pulse Oximetry Monitoring in COVID-19 Patients Discharged From the Emergency Department Identifies Need for Hospitalization. Acad Emerg Med. 2020 Aug;27(8):681-692. doi: 10.1111/acem.14053. Epub 2020 Jul 23. PMID: 32779828; PMCID: PMC7323027.

Objectives: Our objective was to evaluate patient-reported oxygen saturation (SpO2 ) using pulse oximetry as a home monitoring tool for patients with initially nonsevere COVID-19 to identify need for hospitalization.

Methods: Patients were enrolled at the emergency department (ED) and outpatient testing centers. Each patient was given a home pulse oximeter and instructed to record their SpO2 every 8 hours. Patients were instructed to return to the ED for sustained home SpO2 < 92% or if they felt they needed emergent medical attention. Relative risk was used to assess the relation between hospitalization and home SpO2 < 92% in COVID-19-positive patients.

Results: We enrolled 209 patients with suspected COVID-19, of whom 77 patients tested positive for COVID-19 and were included. Subsequent hospitalization occurred in 22 of 77 (29%) patients. Resting home SpO2 < 92% was associated with an increased likelihood of hospitalization compared to SpO2 ≥ 92% (relative risk = 7.0, 95% confidence interval = 3.4 to 14.5, p < 0.0001). Home SpO2 < 92% was also associated with increased risk of intensive care unit admission, acute respiratory distress syndrome, and septic shock. In our cohort, 50% of patients who ended up hospitalized only returned to the ED for incidental finding of low home SpO2 without worsening of symptoms. One-third (33%) of nonhospitalized patients stated that they would have returned to the ED if they did not have a pulse oximeter to reassure them at home.

Conclusions: This study found that home pulse oximetry monitoring identifies need for hospitalization in initially nonsevere COVID-19 patients when a cutoff of SpO2 92% is used. Half of patients who ended up hospitalized had SpO2 < 92% without worsening symptoms. Home SpO2 monitoring also reduces unnecessary ED revisits.

Selhorst P, Van Ierssel S, Michiels J, Mariën J, Bartholomeeusen K, Dirinck E, Vandamme S, Jansens H, Ariën KK. Symptomatic SARS-CoV-2 reinfection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response. Clin Infect Dis. 2020 Dec 14:ciaa1850. doi: 10.1093/cid/ciaa1850. Epub ahead of print. PMID: 33315049.

Background: It is currently unclear whether SARS-CoV-2 reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection.

Methods: A case of reinfection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 health care workers. To distinguish reinfection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the reinfection case’s first episode. IgA, IgM, and IgG and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case.

Results: Reinfection was confirmed in a young, immunocompetent health care worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic reinfection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and virus culture remained inconclusive, the health care worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs.

Conclusion: If this case is representative of most Covid-19 patients, long-lived protective immunity against SARS-CoV-2 after primary infection might not be likely.

Donnelly JP, Wang XQ, Iwashyna TJ, Prescott HC. Readmission and Death After Initial Hospital Discharge Among Patients With COVID-19 in a Large Multihospital System. JAMA. 2020 Dec 14:e2021465. doi: 10.1001/jama.2020.21465. Epub ahead of print. PMID: 33315057; PMCID: PMC7737131.

This study describes reasons for readmission, use of ICU interventions during readmission, and proportions of death after initial hospital discharge of COVID-19 patients from US Veterans Affairs (VA) hospitals March-June 2020.

Doan T, Hinterwirth A, Arzika AM, Worden L, Chen C, Zhong L, Oldenburg CE, Keenan JD, Lietman TM. Reduction of Coronavirus Burden With Mass Azithromycin Distribution. Clin Infect Dis. 2020 Nov 19;71(16):2282-2284. doi: 10.1093/cid/ciaa606. PMID: 32426812; PMCID: PMC7314118.

We evaluated the potential antiviral effects of azithromycin on the nasopharyngeal virome of Nigerien children who had received multiple rounds of mass drug administration. We found that the respiratory burden of non-severe acute respiratory syndrome coronaviruses was decreased with azithromycin distributions.

Deleers M, Breiman A, Daubie V, Maggetto C, Barreau I, Besse T, Clémenceau B, Ruvoën-Clouet N, Fils JF, Maillart E, Doyen V, Mahadeb B, Jani J, der Linden PV, Cannie M, Hayef N, Corazza F, Le Pendu J, Kenz HE. Covid-19 and blood groups: ABO antibody levels may also matter. Int J Infect Dis. 2020 Dec 13:S1201-9712(20)32549-2. doi: 10.1016/j.ijid.2020.12.025. Epub ahead of print. PMID: 33326874.

Background: Susceptibility to Covid-19 has been found to be associated with ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection.

Methods: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies.

Results: We found significantly lower IgM anti-A+ anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls.

Conclusion: In this study, we showed that ABO antibodies levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

Peahl AF, Howell J. The Evolution of Prenatal Care Delivery Guidelines in the United States. Am J Obstet Gynecol. 2020 Dec 11:S0002-9378(20)31391-0. doi: 10.1016/j.ajog.2020.12.016. Epub ahead of print. PMID: 33316276.

The coronavirus disease COVID-19 pandemic led to some of the most drastic changes in clinical care delivery ever seen in the United States. Almost overnight, providers of prenatal care adopted virtual visits and reduced visit schedules. These changes stood in stark contrast to the 12 to 14 in-person prenatal visit schedule than had been previously recommended for almost a century. As maternity care providers consider what prenatal care delivery changes we should maintain following the acute pandemic, we may gain insight from understanding the evolution of prenatal care delivery guidelines. In this paper, we start by sketching out the relatively unstructured beginnings of prenatal care in the 19th century. Most medical care fell within the domain of laypeople, and childbirth was a central feature of female domestic culture. We explore how early discoveries about “toxemia” created the groundwork for future prenatal care interventions, including screening of urine and blood pressure-which in turn created a need for routine prenatal care visits. We then discuss the organization of the medical profession, including the field of obstetrics and gynecology. In the early 20th century, new data increasingly revealed high rates of both infant and maternal mortality, leading to a greater emphasis on prenatal care. These discoveries culminated in the first codification of a prenatal visit schedule in 1930 by the Children’s Bureau. Surprisingly, this schedule remained essentially unchanged for almost a century. Through the founding of the American College of Obstetricians and Gynecologists, significant technological advancements in laboratory testing and ultrasonography, and even an NIH Task Force call for changes in prenatal care delivery in 1989, prenatal care recommendations continued to be the same as they had been in 1930-monthly visits until 28 weeks, bimonthly visits until 36 weeks, and weekly visits until delivery. But COVID-19 forced us to change, to reconsider both the need for in-person visits and the frequency of visits. Now, as we transition from the acute pandemic, we should consider how to use what we have learned in this unprecedented time to shape future prenatal care. Lessons from over a century of prenatal care provide valuable insights to inform the next generation of prenatal care delivery.

Li N, Han L, Peng M, Lv Y, Ouyang Y, Liu K, Yue L, Li Q, Sun G, Chen L, Yang L. Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study. Clin Infect Dis. 2020 Nov 19;71(16):2035-2041. doi: 10.1093/cid/ciaa352. PMID: 32249918; PMCID: PMC7184430.

Background: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia.

Methods: We conducted a case-control study to compare clinical characteristics and maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia.

Results: During the period 24 January-29 February 2020, there were 16 pregnant women with confirmed COVID-19 pneumonia and 18 suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest were cesarean delivery. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest computed tomographic images of COVID-19 pneumonia. Compared to the controls, patients with COVID-19 pneumonia had lower counts of white blood cells (WBCs), neutrophils, C-reactive protein (CRP), and alanine aminotransferase on admission. Increased levels of WBCs, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. Three (18.8%) of the mothers with confirmed COVID-19 pneumonia and 3 (16.7%) with suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than in the control group. None experienced respiratory failure during their hospital stay. COVID-19 infection was not found in the newborns, and none developed severe neonatal complications.

Conclusions: Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal or cesarean delivery. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

Erol SA, Tanacan A, Anuk AT, Tokalioglu EO, Biriken D, Keskin HL, Tekin OM, Yazihan N, Sahin D. Evaluation of Maternal Serum Afamin and Vitamin E Levels in Pregnant Women with COVID-19 and Its Association with Composite Adverse Perinatal Outcomes. J Med Virol. 2020 Dec 12. doi: 10.1002/jmv.26725. Epub ahead of print. PMID: 33314206.

Objective: To evaluate the maternal serum afamin and vitamin E levels in pregnant women with coronavirus disease 2019 (COVID-19) and to investigate their association with composite adverse perinatal outcomes.

Methods: This prospective, case-control study consisted of 60 pregnant women with COVID-19 infection and 36 age-matched pregnant women without any defined risk factors. Demographic features, laboratory test results, afamin and vitamin E levels were compared between the groups. Receiver operating characteristic (ROC) curve was used to assess the relationship of afamin and vitamin E levels in predicting composite adverse perinatal outcomes. A correlation analysis was performed between afamin and C-reactive protein (CRP) levels in pregnant women with COVID-19.

Results: Obstetric complication rate was higher in the COVID-19 group (13.3% vs 2.8%) (p=0.01). Afamin levels were higher and vitamin E levels were lower in the COVID-19 group (p=0.02, p<0.001, respectively). Vitamin E levels were lower in the COVID-19 group for the all trimesters (p<0.001, p<0.001, p=0.004, respectively). Afamin levels were higher in the COVID-19 group for the all trimesters without reaching statistical significance (p>0.05). The values in ROC curves with the best balance of sensitivity/specificity for afamin and vitamin E were 0.424 mg/l (70.6% sensitivity, 44.3% specificity) and 3.150 µg/ml (76.5% sensitivity, 58.2% specificity), respectively. A positive moderate statistically significant correlation was found between afamin and CRP levels (r= 0.264, p=0.009).

Conclusion: Higher afamin and lower vitamin E levels may support the elevated oxidative stress in the etiopathogenesis of COVID-19 and the relationship with composite adverse perinatal outcomes.

Edlow AG, Li JZ, Collier AY, Atyeo C, James KE, Boatin AA, Gray KJ, Bordt EA, Shook LL, Yonker LM, Fasano A, Diouf K, Croul N, Devane S, Yockey LJ, Lima R, Shui J, Matute JD, Lerou PH, Akinwunmi BO, Schmidt A, Feldman J, Hauser BM, Caradonna TM, De la Flor D, D’Avino P, Regan J, Corry H, Coxen K, Fajnzylber J, Pepin D, Seaman MS, Barouch DH, Walker BD, Yu XG, Kaimal AJ, Roberts DJ, Alter G. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020 Dec 1;3(12):e2030455. doi: 10.1001/jamanetworkopen.2020.30455. PMID: 33351086.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection.

Design, setting, and participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2.

Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR.

Main outcomes and measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta.

Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted.

Conclusions and relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

Iscrizioni, diventa socio o rinnova la quota SIN

La SIN è una società, non a fini di lucro, che persegue e allarga gli scopi ed obiettivi del Gruppo di Lavoro di Neonatologia della Società Italiana di Pediatria (SIP).