With schools reopening, an increasing number of custodians are applying disinfectant spray methods to decontaminate frequently touched surfaces, including school supplies, walls, desks, and chairs, to mitigate SARS-CoV-2 virus transmission between students, and teachers and students in the classroom. In this research, we present a novel characterization method to evaluate disinfectant droplet size and coverage for two types of commonly used disinfectant sprayers and suggest the optimum application practice for them.

Importance: Convalescent plasma is a proposed treatment for COVID-19.

Objective: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).

Data sources: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021.

Study selection: The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting.

Data extraction and synthesis: Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Main outcomes and measures: All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events.

Results: A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was -1.21% (95% CI, -5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was -2.56% [95% CI, -13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences.

Conclusions and relevance: Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, setting, and participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main outcomes and measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99).

Conclusions and relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Importance: Clinical effectiveness data on remdesivir are urgently needed, especially among diverse populations and in combination with other therapies.

Objective: To examine whether remdesivir administered with or without corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is associated with more rapid clinical improvement in a racially/ethnically diverse population.

Design, setting, and participants: This retrospective comparative effectiveness research study was conducted from March 4 to August 29, 2020, in a 5-hospital health system in the Baltimore, Maryland, and Washington, DC, area. Of 2483 individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection assessed by polymerase chain reaction, those who received remdesivir were matched to infected individuals who did not receive remdesivir using time-invariant covariates (age, sex, race/ethnicity, Charlson Comorbidity Index, body mass index, and do-not-resuscitate or do-not-intubate orders) and time-dependent covariates (ratio of peripheral blood oxygen saturation to fraction of inspired oxygen, blood pressure, pulse, temperature, respiratory rate, C-reactive protein level, complete white blood cell count, lymphocyte count, albumin level, alanine aminotransferase level, glomerular filtration rate, dimerized plasmin fragment D [D-dimer] level, and oxygen device). An individual in the remdesivir group with k days of treatment was matched to a control patient who stayed in the hospital at least k days (5 days maximum) beyond the matching day.

Exposures: Remdesivir treatment with or without corticosteroid administration.

Main outcomes and measures: The primary outcome was rate of clinical improvement (hospital discharge or decrease of 2 points on the World Health Organization severity score), and the secondary outcome, mortality at 28 days. An additional outcome was clinical improvement and time to death associated with combined remdesivir and corticosteroid treatment.

Results: Of 2483 consecutive admissions, 342 individuals received remdesivir, 184 of whom also received corticosteroids and 158 of whom received remdesivir alone. For these 342 patients, the median age was 60 years (interquartile range, 46-69 years), 189 (55.3%) were men, and 276 (80.7%) self-identified as non-White race/ethnicity. Remdesivir recipients had a shorter time to clinical improvement than matched controls without remdesivir treatment (median, 5.0 days [interquartile range, 4.0-8.0 days] vs 7.0 days [interquartile range, 4.0-10.0 days]; adjusted hazard ratio, 1.47 [95% CI, 1.22-1.79]). Remdesivir recipients had a 28-day mortality rate of 7.7% (22 deaths) compared with 14.0% (40 deaths) among matched controls, but this difference was not statistically significant in the time-to-death analysis (adjusted hazard ratio, 0.70; 95% CI, 0.38-1.28). The addition of corticosteroids to remdesivir was not associated with a reduced hazard of death at 28 days (adjusted hazard ratio, 1.94; 95% CI, 0.67-5.57).

Conclusions and relevance: In this comparative effectiveness research study of adults hospitalized with COVID-19, receipt of remdesivir was associated with faster clinical improvement in a cohort of predominantly non-White patients. Remdesivir plus corticosteroid administration did not reduce the time to death compared with remdesivir administered alone.

Punti nascita, le società scientifiche a Bonaccini: “Perplessità sulle riaperture”

Objective: Previous observational studies suggested that increased cardiac markers are commonly found in COVID-19. This study aimed to determine the relationship between several cardiac markers and the severity/mortality of COVID-19 patients.

Methods: We analysed several cardiac markers in this meta-analysis. RevMan 5.4 was used to provide pooled estimates for standardized mean difference (SMD) with 95% confidence intervals.

Results: Twenty nine clinical studies were included in this meta-analysis. This study found significantly higher CKMB (0.64, 95% CI = 0.19-1.09,), PCT (0.47, 95% CI = 0.26-0.68), NT-proBNP (1.90, 95% CI = 1.63-2.17), BNP (1.86, 95% CI = 1.63-2.09), and D-dimer (1.30, 95% CI = 0.91-1.69) in severe compared to non-severe COVID-19. This study also found significantly higher CKMB (3.84, 95% CI = 0.62-7.05), PCT (1.49, 95% CI = 0.86-2.13), NT-proBNP (4.66, 95% CI = 2.42-6.91,), BNP (1.96, 95% CI = 0.78-3.14), troponin (1.64 (95% CI = 0.83-2.45), and D-dimer (2.72, 95% CI = 2.14-3.29) in death cases compared to survived cases with COVID-19.

Conclusions: In conclusion, high CKMB, PCT, NT-proBNP, BNP, and D-dimer could be predictive markers for the severity of COVID-19, while high CKMB, PCT, NT-proBNP, BNP, troponin, and D-dimer could be predictive markers for the survival of COVID-19 patients.

Background: Cardiac injury is frequently encountered in patients with coronavirus disease 2019 (COVID-19) and is associated with increased risk of mortality. Elevated troponin may signify myocardial damage and is predictive of mortality. This study aimed to assess the prognostic value of troponin above the 99th percentile upper reference limit (URL) for mortality, and factors affecting the relationship.

Methods: A comprehensive literature search of PubMed (MEDLINE), Scopus and Embase was undertaken, from inception of the databases until 16 December 2020. The key exposure was elevated serum troponin, defined as troponin (of any type) above the 99th percentile URL. The outcome was mortality due to any cause.

Results: In total, 12,262 patients from 13 studies were included in this systematic review and meta-analysis. The mortality rate was 23% (20-26%). Elevated troponin was observed in 31% (23-38%) of patients. Elevated troponin was associated with increased mortality [odds ratio (OR) 4.75, 95% confidence interval (CI) 4.07-5.53; P < 0.001; I2 = 19.9%]. Meta-regression showed that the association did not vary with age (P = 0.218), male gender (P = 0.707), hypertension (P = 0.182), diabetes (P = 0.906) or coronary artery disease (P = 0864). The association between elevated troponin and mortality had sensitivity of 0.55 (0.44-0.66), specificity of 0.80 (0.71-0.86), positive likelihood ratio of 2.7 (2.2-3.3), negative likelihood ratio of 0.56 (0.49-0.65), diagnosis odds ratio of 5 (4-5) and area under the curve of 0.73 (0.69-0.77). The probability of mortality was 45% in patients with elevated troponin and 14% in patients with non-elevated troponin.

Conclusion: Elevated troponin was associated with mortality in patients with COVID-19 with 55% sensitivity and 80% specificity.

Background: National and international guidelines differ about the optimal physical distancing between students for prevention of SARS-CoV-2 transmission; studies directly comparing the impact of ≥3 versus ≥6 feet of physical distancing policies in school settings are lacking. Thus, our objective was to compare incident cases of SARS-CoV-2 in students and staff in Massachusetts public schools among districts with different physical distancing requirements. State guidance mandates masking for all school staff and for students in grades 2 and higher; the majority of districts required universal masking.

Methods: Community incidence rates of SARS-CoV-2, SARS-CoV-2 cases among students in grades K-12 and staff participating in-person learning, and district infection control plans were linked. Incidence rate ratios (IRR) for students and staff members in districts with ≥3 versus ≥6 feet of physical distancing were estimated using log-binomial regression; models adjusted for community incidence are also reported.

Results: Among 251 eligible school districts, 537,336 students and 99,390 staff attended in-person instruction during the 16-week study period, representing 6,400,175 student learning weeks and 1,342,574 staff learning weeks. Student case rates were similar in the 242 districts with ≥3 feet versus ≥6 feet of physical distancing between students (IRR, 0.891, 95% CI, 0.594-1.335); results were similar after adjusting for community incidence (adjusted IRR, 0.904, 95% CI, 0.616-1.325). Cases among school staff in districts with ≥3 feet versus ≥6 feet of physical distancing were also similar (IRR, 1.015, 95% CI, 0.754-1.365).

Conclusions: Lower physical distancing policies can be adopted in school settings with masking mandates without negatively impacting student or staff safety.

COVID-19 vaccine trials provide valuable insight into the safety and efficacy of vaccines, with individually-randomized, placebo-controlled trials being the gold standard in trial design. However, a myriad of variables must be considered as clinical trial data are interpreted and used to guide policy decisions. These variables include factors such as the characteristics of the study population and circulating SARS-CoV-2 strains, the force of infection, the definition and ascertainment of endpoints, the timing of vaccine efficacy assessment, and the potential for performance bias. In this Viewpoint, we discuss critical variables to consider when comparing efficacy measurements across current and future COVID-19 vaccine trials.

We describe 3 instances of SARS-CoV-2 transmission despite medical masks and eye protection, including transmission despite the source person being masked, transmission despite the exposed person being masked, and transmission despite both parties being masked. Whole genome sequencing confirmed perfect homology between source and exposed persons’ viruses in all cases.

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 μg and 6 μg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28.

Methods: We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12-65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT50) and the microneutralisation test (MNT50). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at ClinicalTrials.gov, NCT04471519.

Findings: Between Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 μg with Algel-IMDG group (n=190) or 6 μg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT50) at day 56 were significantly higher in the 6 μg with Algel-IMDG group (197·0 [95% CI 155·6-249·4]) than the 3 μg with Algel-IMDG group (100·9 [74·1-137·4]; p=0·0041). Seroconversion based on PRNT50 at day 56 was reported in 171 (92·9% [95% CI 88·2-96·2] of 184 participants in the 3 μg with Algel-IMDG group and 174 (98·3% [95·1-99·6]) of 177 participants in the 6 μg with Algel-IMDG group. GMTs (MNT50) at day 56 were 92·5 (95% CI 77·7-110·2) in the 3 μg with Algel-IMDG group and 160·1 (135·8-188·8) in the 6 μg with Algel-IMDG group. Seroconversion based on MNT50 at day 56 was reported in 162 (88·0% [95% CI 82·4-92·3]) of 184 participants in the 3 μg with Algel-IMDG group and 171 (96·6% [92·8-98·8]) of 177 participants in the 6 μg with Algel-IMDG group. The 3 μg with Algel-IMDG and 6 μg with Algel-IMDG formulations elicited T-cell responses that were biased to a Th1 phenotype at day 42. No significant difference in the proportion of participants who had a solicited local or systemic adverse reaction in the 3 μg with Algel-IMDG group (38 [20·0%; 95% CI 14·7-26·5] of 190) and the 6 μg with Algel-IMDG group (40 [21·1%; 15·5-27·5] of 190) was observed on days 0-7 and days 28-35; no serious adverse events were reported in the study. From the phase 1 trial, 3-month post-second-dose GMTs (MNT50) were 39·9 (95% CI 32·0-49·9) in the 3μg with Algel-IMDG group, 69·5 (53·7-89·9) in the 6 μg with Algel-IMDG group, 53·3 (40·1-71·0) in the 6 μg with Algel group, and 20·7 (14·5-29·5) in the Algel alone group.

Interpretation: In the phase 1 trial, BBV152 induced high neutralising antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes, and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial.

Objectives: To compare clinical characteristics and outcomes of infants born to COVID-19 to non COVID-19 mothers at delivery in a community hospital in Queens, New York.

Methods: Case-control study conducted March 15 to June 15, 2020. Cases were infants born to mothers with laboratory-confirmed COVID-19 infection at delivery. The infant of non COVID-19 mother born before and after each case were selected as controls.

Results: Of 695 deliveries, 62 (8.9%) infants were born to COVID-19 mothers; 124 controls were selected. Among cases, 18.3% were preterm compared to 8.1% in controls (p=0.04). In preterm cases, birth weight was not significantly different between groups. However, there was a significantly higher proportion of neonatal intensive care unit (NICU) admissions, need for respiratory support, suspected sepsis, hyperbilirubinemia, feeding intolerance and longer length of stay (LOS) in preterm cases. Among term cases, birth weight and adverse outcomes were not significantly different between cases and controls except for more feeding intolerance in cases. All infants born to COVID-19 mothers were COVID-19 negative at 24 and 48 h of life. No infants expired during birth hospitalization.

Conclusions: Significantly, more infants of COVID-19 mothers were premature compared to controls. Preterm cases were more likely to have adverse outcomes despite having similar birth weight and gestational age. These differences were not seen among full term infants. Health care providers should anticipate the need for NICU care when a COVID-19 mother presents in labor.

In order to investigate the clinical features of pregnant women and their neonates with coronavirus disease 2019 (COVID-19) and the evidence of vertical transmission of COVID-19, we retrieved studies included in PubMed, Medline and Chinese databases from January 1, 2000 to October 25, 2020 using relevant terms, such as ‘COVID-19’, ‘vertical transmission’ et al. in ‘Title/Abstract’. Case reports and case series were included according to the inclusion and exclusion criteria. We conducted literature screening and data extraction, and performed literature bias risk assessment. Total of 13 case series and 16 case reports were collected, including a total of 564 pregnant women with COVID-19 and their 555 neonates, of which 549 neonates received nucleic acid test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 18 neonates was diagnosed with COVID-19. The positive rate is 3.28%. Amniotic fluid of one woman was tested positive for SARS-CoV-2. The majority of infected neonates were born under strict infection control and received isolation and artificial feeding. Up till now, there is no sufficient evidence to exclude the possibility of vertical transmission for COVID-19 based on the current available data.

Background: Lung ultrasound (LUS) and lung ultrasound score (LUSS) have been successfully used to diagnose neonatal pneumonia, assess the lesion distribution, and quantify the aeration loss. The present study design determines the diagnostic value of LUSS in the semi-quantitative assessment of pneumonia in coronavirus disease 2019 (COVID-19) neonates.

Methods: Eleven COVID-19 neonates born to mothers with COVID-19 infection and 11 age- and gender-matched controls were retrospectively studied. LUSS was acquired by assessing the lesions and aeration loss in 12 lung regions per subject.

Results: Most of the COVID-19 newborns presented with mild and atypical symptoms, mainly involving respiratory and digestive systems. In the COVID-19 group, a total of 132 regions of the lung were examined, 83 regions (62.8%) of which were detected abnormalities by LUS. Compared with controls, COVID-19 neonates showed sparse or confluent B-lines (83 regions), disappearing A-lines (83 regions), abnormal pleural lines (29 regions), and subpleural consolidations (2 regions). The LUSS was significantly higher in the COVID-19 group. In total, 49 regions (37%) were normal, 73 regions (55%) scored 1, and 10 regions (8%) scored 2 by LUSS. All the lesions were bilateral, with multiple regions involved. The majority of the lesions were located in the bilateral inferior and posterior regions. LUS detected abnormalities in three COVID-19 neonates with normal radiological performance. The intra-observer and inter-observer reproducibility of LUSS was excellent.

Conclusions: LUS is a noninvasive, convenient, and sensitive method to assess neonatal COVID-19 pneumonia, and can be used as an alternative to the use of diagnostic radiography. LUSS provides valuable semi-quantitative information on the lesion distribution and severity.

Purpose of review: To provide an update on the consequences of severe acute respiratory syndrome (SARS)-CoV-2 infection on the health and perinatal outcomes of pregnant women and their infants.

Recent findings: The severity of SARS-CoV-2 infection is greater in pregnant compared to nonpregnant women as measured by rates of admission to intensive care units, mechanical ventilation, mortality, and morbidities including myocardial infarction, venous thromboembolic and other thrombotic events, preeclampsia, preterm labor, and preterm birth. The risk of transmission from mother-to-infant is relatively low (1.5-5%) as quantitated by neonatal SARS-CoV-2 testing. Infants appear to be at higher risk of testing positive for SARS-CoV-2 if the mother has tested positive within 1 week of delivery or is herself symptomatic at the time of maternity admission. The rate of positivity is not higher in infants who room in with the mother compared to infants who are initially separated and cared for in a SARS-CoV-2-free environment. Infants who test positive in the hospital have no or mild signs of disease, most of which may be attributable to prematurity, and rarely require readmission for clinical signs consistent with COVID-19.

Summary: Pregnant women should take precautions to avoid infection with SARS-CoV-2. Infants born to mothers who test positive for SARS-CoV-2 can receive normal neonatal care in-hospital with their mothers if mother and staff adhere to recommended infection control practices.

Objective: There is a paucity of evidence to guide the clinical care of late preterm and term neonates born to women with perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The objective of this case series is to describe early neonatal outcomes and inpatient management in U.S. hospitals.

Study design: We solicited cases of mother-infant dyads affected by novel coronavirus disease 2019 (COVID-19) from the Better Outcomes through Research for Newborns (BORN) Network members. Using a structured case template, participating sites contributed deidentified, retrospective birth hospitalization data for neonates ≥35 weeks of gestation at birth with mothers who tested positive for SARS-CoV-2 before delivery. We describe demographic and clinical characteristics, clinical management, and neonatal outcomes.

Results: Sixteen U.S. hospitals contributed 70 cases. Birth hospitalizations were uncomplicated for 66 (94%) neonates in which 4 (6%) required admission to a neonatal intensive care unit. None required evaluation or treatment for infection, and all who were tested for SARS-CoV-2 were negative (n = 57). Half of the dyads were colocated (n = 34) and 40% directly breastfed (n = 28). Outpatient follow-up data were available for 13 neonates, all of whom remained asymptomatic.

Conclusion: In this multisite case series of 70 neonates born to women with SARS-CoV-2 infection, clinical outcomes were overall good, and there were no documented neonatal SARS-CoV-2 infections. Clinical management was largely inconsistent with contemporaneous U.S. COVID-19 guidelines for nursery care, suggesting concerns about the acceptability and feasibility of those recommendations. Longitudinal studies are urgently needed to assess the benefits and harms of current practices to inform evidence-based clinical care and aid shared decision-making.

Key points: · Birth hospitalizations were uncomplicated for late preterm and term infants with maternal COVID-19.. · Nursery management of dyads affected by COVID-19 varied between hospitals.. · Adherence to contemporaneous U.S. clinical guidelines for nursery care was low.. · Breastfeeding rates were lower for dyads roomed separately than those who were colocated..

Background: Predicting the clinical trajectory of individual patients hospitalized with coronavirus disease 2019 (COVID-19) is challenging but necessary to inform clinical care. The majority of COVID-19 prognostic tools use only data present upon admission and do not incorporate changes occurring after admission.

Objective: To develop the Severe COVID-19 Adaptive Risk Predictor (SCARP) (https://rsconnect.biostat.jhsph.edu/covid_trajectory/), a novel tool that can provide dynamic risk predictions for progression from moderate disease to severe illness or death in patients with COVID-19 at any time within the first 14 days of their hospitalization.

Design: Retrospective observational cohort study.

Setting: Five hospitals in Maryland and Washington, D.C.

Patients: Patients who were hospitalized between 5 March and 4 December 2020 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed by nucleic acid test and symptomatic disease.

Measurements: A clinical registry for patients hospitalized with COVID-19 was the primary data source; data included demographic characteristics, admission source, comorbid conditions, time-varying vital signs, laboratory measurements, and clinical severity. Random forest for survival, longitudinal, and multivariate (RF-SLAM) data analysis was applied to predict the 1-day and 7-day risks for progression to severe disease or death for any given day during the first 14 days of hospitalization.

Results: Among 3163 patients admitted with moderate COVID-19, 228 (7%) became severely ill or died in the next 24 hours; an additional 355 (11%) became severely ill or died in the next 7 days. The area under the receiver-operating characteristic curve (AUC) for 1-day risk predictions for progression to severe disease or death was 0.89 (95% CI, 0.88 to 0.90) and 0.89 (CI, 0.87 to 0.91) during the first and second weeks of hospitalization, respectively. The AUC for 7-day risk predictions for progression to severe disease or death was 0.83 (CI, 0.83 to 0.84) and 0.87 (CI, 0.86 to 0.89) during the first and second weeks of hospitalization, respectively.

Limitation: The SCARP tool was developed by using data from a single health system.

Conclusion: Using the predictive power of RF-SLAM and longitudinal data from more than 3000 patients hospitalized with COVID-19, an interactive tool was developed that rapidly and accurately provides the probability of an individual patient’s progression to severe illness or death on the basis of readily available clinical information.

Background: Patients with COVID-19 can present to the emergency department (ED) at any point during the spectrum of illness, making it difficult to predict what level of care the patient will ultimately require. Admission to a ward bed, which is subsequently upgraded within hours to an intensive care unit (ICU) bed, represents an inability to appropriately predict the patient’s course of illness. Predicting which patients will require ICU care within 24 hours would allow admissions to be managed more appropriately.

Methods: This was a retrospective study of adults admitted to a large healthcare system, including 14 hospitals across the state of Indiana. Included patients were aged ≥ 18 years, were admitted to the hospital from the ED, and had a positive PCR test for COVID-19. Patients directly admitted to the ICU or in whom the PCR test was obtained > 3 days after hospital admission were excluded. Extracted data points included demographics, comorbidities, ED vital signs, laboratory values, chest imaging results, and level of care on admission. The primary outcome was a combination of either death or transfer to ICU within 24 hours of admission to the hospital. Data analysis was performed by logistic regression modeling to determine a multivariable model of variables that could predict the primary outcome.

Results: Of the 542 included patients, 46 (10%) required transfer to ICU within 24 hours of admission. The final composite model, adjusted for age and admission location, included history of heart failure, initial oxygen saturation of <93%, plus either WBC > 6.4 or GFR < 46. The odds ratio for decompensation within 24 hours was 5.17 (CI 2.17-12.31) when all criteria were present. For patients without the above criteria, the odds ratio for ICU transfer was 0.20 (0.09 to 0.45).

Conclusions: Although our model did not perform well enough to stand alone as a decision guide, it highlights certain clinical features which are associated with increased risk of decompensation.

We describe the first infant born to a woman with COVID-19 in Vietnam, by Caesarean section at 36 weeks and five days of gestation. The mother and baby remained together during their hospital stay and prolonged skin-to-skin contact and early and exclusive breastfeeding were achieved. This was in line with the World Health Organization’s Early Essential Newborn Care (EENC) recommendations, the national Vietnamese standard of care since 2014. The baby remained virus free throughout the 34-day postpartum follow up. CONCLUSION: The EENC approach can still be used with mothers who have COVID-19 if effective infection control measures are applied.

Amidst the evolving COVID-19 pandemic and its precarious conditions that have impacted the worldwide community, the need to achieve a herd immunity through immunization has become the only resort to control this horrendous pandemic.

Introduction: Teicoplanin has a potential antiviral activity expressed against SARS-CoV-2 and was suggested as a complementary option to treat COVID-19 patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID-19 in critically ill patients.

Methods: 55 patients with severe COVID-19, hospitalized in the ICUs and treated with best available therapy were retrospectively analysed. Among them 34 patients were also treated with teicoplanin (Tei-COVID group), while 21 without teicoplanin (control group).

Results: Crude in-hospital day-30 mortality was lower in Tei-COVID group (35,2%) than in control group (42,8%), however not reaching statistical significance (p = 0.654). No statistically significant differences in length of stay in the ICU were observed between Tei-COVID group and control group (p = 0.248). On day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei-COVID group and 57.1% of control group, without statistical difference. Serum C reactive Protein level was significantly reduced in Tei-COVID group compared to control group, but not other biochemical parameters. Finally, Gram-positive were the causative pathogens for 25% of BSIs in Tei-COVID group and for 70,6% in controls. No side effects related to teicoplanin use were observed.

Conclusion: Despite several limitations require further research, in this study the use of teicoplanin is not associated with a significant improvement in outcomes analysed. The antiviral activity of teicoplanin against SARS-CoV-2, previously documented, is probably more effective at early clinical stages

Introduction: The impact of maternal SARS-CoV-2 infection and its risk of vertical transmission is still not well known. Recommendations from scientific societies seek to provide safety for newborns without compromising the benefits of early contact. The aim of the study is to describe characteristics and evolution of newborns born to mothers with SARS-CoV-2 infection, as well as the implemented measures following recommendations from the Sociedad Española de Neonatología.

Methods: Observational, prospective and single-center cohort study. A specific circuit was designed for mothers with SARS-CoV-2 infection and their newborns. Epidemiological and clinical data were collected. PCR were performed in newborns at delivery and at 14 days of age.

Results: 73 mothers and 75 newborns were included in the study. 95.9% of maternal infections were diagnosed during the third trimester of pregnancy, 43.8% were asymptomatic. Median gestational age was 38 weeks (IQR: 37-40), 25.9% of newborns required admission to Neonatology. Skin-to-skin mother care was performed in 68% of newborns, 80% received exclusive maternal or donated breast milk during hospital stay. No positive PCR results were observed in newborns at delivery, one case of positive PCR was observed in an asymptomatic neonate at 14 days of age.

Conclusions: Risk of SARS-CoV-2 transmission is low when complying to the recommendations issued by Sociedad Española de Neonatología, allowing rooming-in and promoting breastfeeding.

Objective: The impact of evolving guidelines and clinical practices on SARS-CoV-2-positive dyads across New York City Health and Hospitals during the early peak of COVID-19.

Design: A retrospective cohort study of positive-positive (P/P), positive-negative (P/N), and positive-untested (P/U) dyads delivered from March 1 to May 9, 2020. Wilcoxon rank sum, Chi-squared, and Fisher exact tests were used to analyze demographics, clinical variables, and system-wide management practices.

Result: A total of 2598 mothers delivered. 23.8% (286/1198) of mothers tested for SARS-CoV-2 were positive. 89.7% (260/290) newborns of SARS-CoV-2-positive mothers were tested and 11 were positive. Positive-positive newborns were more likely to be breastfed (81%), be admitted to NICU, and have longer length of stay (7.5 days) than P/N and P/U newborns.

Conclusion: Our study shows that varied testing, feeding, and isolation practices resulted in favorable short-term outcomes for SARS-CoV-2-positive mothers and their newborns. High-risk populations can be safely and effectively treated in resource-limited environments.

Objective: To compare the risk of intrauterine fetal death (20 weeks of gestation or later) and neonatal death among individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with those who tested negative for SARS-CoV-2 on admission for delivery.

Data sources: MEDLINE, Ovid, EMBASE, Cumulative Index to Nursing and Allied Health, and Cochrane Library were searched from their inception until July 17, 2020. Hand search for additional articles continued through September 24, 2020. ClinicalTrials.gov was searched on October 21, 2020.

Methods of study selection: The inclusion criteria were publications that compared at least 20 cases of both pregnant patients who tested positive for SARS-CoV-2 on admission to labor and delivery and those who tested negative. Exclusion criteria were publications with fewer than 20 individuals in either category or those lacking data on primary outcomes. A systematic search of the selected databases was performed, with co-primary outcomes being rates of intrauterine fetal death and neonatal death. Secondary outcomes included rates of maternal and neonatal adverse outcomes.

Tabulation, integration, and results: Of the 941 articles and completed trials identified, six studies met criteria. Our analysis included 728 deliveries to patients who tested positive for SARS-CoV-2 and 3,836 contemporaneous deliveries to patients who tested negative. Intrauterine fetal death occurred in 8 of 728 (1.1%) patients who tested positive and 44 of 3,836 (1.1%) who tested negative (P=.60). Neonatal death occurred in 0 of 432 (0.0%) patients who tested positive and 5 of 2,400 (0.2%) who tested negative (P=.90). Preterm birth occurred in 95 of 714 (13.3%) patients who tested positive and 446 of 3,759 (11.9%) who tested negative (P=.31). Maternal death occurred in 3 of 559 (0.5%) patients who tested positive and 8 of 3,155 (0.3%) who tested negative (P=.23).

Conclusion: The incidences of intrauterine fetal death and neonatal death were similar among individuals who tested positive compared with negative for SARS-CoV-2 when admitted to labor and delivery. Other immediate outcomes of the newborns were also similar among those born to individuals who tested positive compared with negative for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has spread worldwide within a short period, and there is still no sign of an end to the pandemic. Management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant women at the time of delivery presents a unique challenge. To fulfill the goal of providing adequate management of such women and their infants, and to decrease the risk of exposure of the healthcare providers, tentative guidelines are needed until more evidence is collected. Practical preventative action is required that takes into account the following infection routes: (i) aerosol transmission from mothers to healthcare providers, (ii) horizontal transmission to healthcare providers from infants infected by their mothers, and (iii) horizontal transmission from mothers to infants. To develop standard operating procedures, briefings/training simulations should be carried out, taking into account the latest information. Briefings should be carefully conducted to clarify the role and procedures. Healthcare providers should wear personal protective equipment. If it is physically possible, neonatal resuscitation should be performed in a separate area next to the delivery room. If a separate area is not available, the infant warmer should be placed at least 2 m away from the delivery table, or partitioned off in the same room. A minimum number of skilled personnel should participate in resuscitation using the latest neonatal resuscitation algorithms.

Background: Studies evaluating the safety and efficacy of currently available vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not include pregnant participants. No data are available to counsel on vaccine safety and potential for neonatal passive immunity.

Case: A 34-year-old multigravid patient working in health care received the Pfizer-BioNTech (BNT162b2) mRNA vaccine for SARS-CoV-2 in the third trimester of pregnancy. Uncomplicated spontaneous vaginal delivery of a female neonate with Apgar scores of 9 and 9 occurred at term. The patient’s blood as well as neonatal cord blood were evaluated for SARS-CoV-2-specific antibodies. Both the patient and the neonate were positive for antibodies at a titer of 1:25,600.

Conclusion: In this case, passage of transplacental antibodies for SARS-CoV-2 was shown after vaccination in the third trimester of pregnancy.

Background: The impact of delivery mode on the infection rates of Coronavirus disease 2019 (COVID-19) in the newborn remains unknown. We aimed to summarize the existing literature on COVID-19 infection during pregnancy to evaluate which mode of delivery is better for preventing possible vertical transmission from a pregnant mother confirmed with COVID-19 to a neonate. Methods: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, and the Chinese Biomedical Literature database (CBM) from 31 December 2019 to 18 June 2020. We applied no language restrictions. We screened abstracts for relevance, extracted data, and assessed the risk of bias in duplicate. We rated the certainty of evidence using the GRADE approach. The primary outcome was severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity in neonates born to mothers with confirmed COVID-19 following different delivery modes. Secondary outcomes were neonatal deaths and maternal deaths. This study is registered with PROSPERO, CRD42020194049. Results: Sixty-eight observational studies meeting inclusion criteria were included in the current study, with no randomized controlled trials. In total, information on the mode of delivery, detailed neonatal outcomes, and SARS-CoV-2 status were available for 1,019 pregnant women and 1,035 neonates. Six hundred and eighteen (59.71%) neonates were born through cesarean section and 417(40.29%) through vaginal delivery. Probable congenital SARS-CoV-2 infections were reported in 34/1,035 (3.29%) neonates. Of babies born vaginally, 9/417 (2.16%) were tested positive compared with 25/618 (4.05%) born by cesarean. Of babies born vaginally, 0/417 (0.00%) neonatal deaths were reported compared with 6/618 (0.97%) born by cesarean. Of women who delivered vaginally, 1/416 (0.24%) maternal deaths were reported compared with 11/603 (1.82%) delivered by cesarean. Two women died before delivery. Sensitivity analyses and subgroup analyses showed similar findings. Conclusions: The rate of neonatal COVID-19 infection, neonatal deaths, and maternal deaths are no greater when the mother gave birth through vaginal delivery. Based on the evidence available, there is no sufficient evidence supporting that the cesarean section is better than vaginal delivery in preventing possible vertical transmission from a pregnant mother confirmed with COVID-19 to a neonate. The mode of birth should be individualized and based on disease severity and obstetric indications. Additional good-quality studies with comprehensive serial tests from multiple specimens are urgently needed.

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.

Methods: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005).

Findings: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]).

Interpretation: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose.

Adherence to non-pharmaceutical interventions to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been highly variable across settings, particularly in the USA. In this Personal View, we review data supporting the importance of the viral inoculum (the dose of viral particles from an infected source over time) in increasing the probability of infection in respiratory, gastrointestinal, and sexually transmitted viral infections in humans. We also review the available evidence linking the relationship of the viral inoculum to disease severity. Non-pharmaceutical interventions might reduce the susceptibility to SARS-CoV-2 infection by reducing the viral inoculum when there is exposure to an infectious source. Data from physical sciences research suggest that masks protect the wearer by filtering virus from external sources, and others by reducing expulsion of virus by the wearer. Social distancing, handwashing, and improved ventilation also reduce the exposure amount of viral particles from an infectious source. Maintaining and increasing non-pharmaceutical interventions can help to quell SARS-CoV-2 as we enter the second year of the pandemic. Finally, we argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed.

Background and aims: Zinc inhibits replication of the SARS-CoV virus. We aimed to evaluate the safety, feasibility and biological effect of administering high-dose intravenous zinc (HDIVZn) to patients with COVID-19.

Methods: We performed a phase IIa double-blind, randomised controlled trial to compare HDIVZn to placebo in hospitalised patients with COVID-19. We administered trial treatment once daily for a maximum of seven days until either death or hospital discharge. We measured zinc concentration at baseline and during treatment and observed patients for any significant side effects.

Results: For eligible patients, we randomised and administered treatment to 33 adult participants to either HDIVZn (n=15) or placebo (n=18). We observed no serious adverse events throughout the study for a total of 94 HDIVZn administrations. However, 3 participants in the HDIVZn group reported infusion site irritation. Mean serum zinc on day 1 in the placebo, and the HDIVZn group was 6.9 ± 1.1 and 7.7 ± 1.6 µmol/l, respectively, consistent with zinc deficiency. HDIVZn, but not placebo, increased serum zinc levels above the deficiency cut off of 10.7 µmol/l (P<0.001) by day 6. Our study did not reach its target enrolment because stringent public health measures markedly reduced patient hospitalisations.

Conclusion: Hospitalised COVID-19 patients demonstrated zinc deficiency. This can be corrected with HDIVZn. Such treatment appears safe, feasible and only associated with minimal peripheral infusion site irritation. This pilot study justifies further investigation of this treatment in COVID-19 patients

To assess the prevalence of persistent functional impairment after COVID-19, we assessed 118 individuals 3-4 months after their initial COVID-19 diagnosis with a symptom survey, work productivity and activity index questionnaire, and 6-minute walk test. We found significant persistent symptoms and functional impairment, even in non-hospitalized patients with COVID-19.

The clinical course of COVID-19 is very heterogeneous: Most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. We performed a biomarker study to assess the impact of prior infections with seasonal coronaviruses on COVID-19 severity. 60 patients with confirmed COVID-19 infections were included (age 30 – 82 years; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients with severe or moderate disease and 25 outpatients. Patients with critical disease had significantly lower levels of anti-HCoV OC43-NP (p = 0.016) and HCoV HKU1-NP (p = 0.023) antibodies at the first encounter compared to other COVID-19 patients. Our results indicate that prior infections with seasonal coronaviruses might protect against a severe course of disease.

Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

Background: COVID19 is caused by a newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) that affects pregnant women equally to the general population. How SARS-CoV2 affects the mothers, the neonates and the placental pathology remain controversial.

Objective: To explore the effects of maternal SARS-CoV2 infection on the neonates and placental pathology in comparison to those from the normal pregnancies.

Study design: Maternal, neonatal and placental pathology data were collected from medical records between March and August 2020 from New York Presbyterian- Brooklyn Methodist Hospital. The data from a total 142 neonates and 101 placentas from SARS-CoV2 positive mothers were compared with those from SARS-CoV2 negative mothers.

Results: There were 142 SARS-CoV2 positive mothers within the study group, and 43 (36%) of them showed various degrees of COVID19 related clinical symptoms including fever (13.8%), cough (5.7%), loss of taste/smell (anosmia)(5.6%), shortness of breath (2.4%), muscle ache (2.4%), headache (1.6%) and pneumonia (0.8%). A total 142 neonates were born to the SARS-CoV-2 positive mothers, and only 1 neonate tested positive for SARS-CoV2 in the first 24 h. Two additional neonates were initially tested negative in first 24 h, and later tested positive on day 7 and the 1 month visit, and all these neonates were asymptomatic and had no sequelae. There was no increase of pre-term labor and delivery or NICU admissions from SARS-CoV2 positive mothers. Examination of 101 placentas from SARS-CoV2 positive mothers and 121 placentas from SARS-CoV2 negative mothers revealed no increase of placental pathologic features. There were more vaginal deliveries and more meconium stain of fetal membranes from the SARS-CoV2 positive mothers. Previous reports of more maternal vascular malperfusion and fetal vascular malperfusion were not demonstrated in our current data.

Conclusion: Although SARS-CoV2 is a significant risk to the pregnant women (mothers) and general population, there is no increased risk for neonates. Vertical transmission is rare, and perinatal transmission can also occur. There is no increased frequency of placental abnormalities in both maternal and fetal circulation.

Objective: This study aimed to estimate the prevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) among pregnant patients at the time of delivery in a rural Midwest tertiary care hospital and to examine demographics, clinical factors, and maternal and neonatal outcomes associated with SARS-CoV-2 infection during pregnancy.

Study design: This prospective cohort study included all delivering patients between May 1 and September 22, 2020 at the University of Iowa Hospitals and Clinics. Plasma SARS-CoV-2 antibody testing was performed. SARS-CoV-2 viral reverse-transcription polymerase chain reaction (RT-PCR) results and maternal and neonatal outcomes were collected from the electronic medical record. Data were analyzed using univariate statistical methods with clustering for multiple births.

Results: In total, 1,000 patients delivered between May 1 and September 22, 2020. Fifty-eight (5.8%) were SARS-CoV-2 antibody positive. Twenty-three also tested viral positive during pregnancy. Three of 1,000 (0.3%) were viral positive on admission but antibody negative. The median age was 30 years (interquartile range [IQR]: 26-33 years) and body mass index was 31.75 kg/m2 (IQR 27.7-37.5 kg/m2). The cesarean delivery rate was 34.0%. The study population was primarily white (71.6%); however, 41.0% of SARS-CoV-2 infected patients identified as Black, 18.0% as Hispanic/Latino, 3.3% as Native Hawaiian/Pacific Islander, and only 27.9% as White (p < 0.0001). SARS-CoV-2 infection was more likely in patients without private insurance (p = 0.0243). Adverse maternal and/or neonatal outcomes were not more likely in patients with evidence of infection during pregnancy. Two SARS-CoV-2 infected patients were admitted to the intensive care unit. There were no maternal deaths during the study period.

Conclusion: In this largely rural Midwest population, 6.1% of delivering patients had evidence of past or current SARS-CoV-2 infection. Rates of SARS-CoV-2 during pregnancy were higher among racial and ethnic minorities and patients without private insurance. The SARS-CoV-2 infected patients and their neonates were not found to be at increased risk for adverse outcomes.

Purpose of review: To provide an update on the consequences of severe acute respiratory syndrome (SARS)-CoV-2 infection on the health and perinatal outcomes of pregnant women and their infants.

Recent findings: The severity of SARS-CoV-2 infection is greater in pregnant compared to nonpregnant women as measured by rates of admission to intensive care units, mechanical ventilation, mortality, and morbidities including myocardial infarction, venous thromboembolic and other thrombotic events, preeclampsia, preterm labor, and preterm birth. The risk of transmission from mother-to-infant is relatively low (1.5-5%) as quantitated by neonatal SARS-CoV-2 testing. Infants appear to be at higher risk of testing positive for SARS-CoV-2 if the mother has tested positive within 1 week of delivery or is herself symptomatic at the time of maternity admission. The rate of positivity is not higher in infants who room in with the mother compared to infants who are initially separated and cared for in a SARS-CoV-2-free environment. Infants who test positive in the hospital have no or mild signs of disease, most of which may be attributable to prematurity, and rarely require readmission for clinical signs consistent with COVID-19.

Summary: Pregnant women should take precautions to avoid infection with SARS-CoV-2. Infants born to mothers who test positive for SARS-CoV-2 can receive normal neonatal care in-hospital with their mothers if mother and staff adhere to recommended infection control practices.

Objective: The influence of previous viral symptoms on the level and duration of human milk antibodies reactive to SARS-CoV-2, and common human coronaviruses (HCoVs) was investigated.

Study design: Antibodies reactive to S1 and S2 subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E were measured via ELISA in human milk samples collected from March to June 2020 in mothers with and without viral symptoms.

Results: The presence of viral symptoms influenced the levels of SARS-CoV-2 S2-reactive SIgA/IgA and tended to influence SARS-CoV-2 S1 SIgA/IgA and S2-reactive SIgM/IgM in human milk but did not relate to IgG. HCoV-229E S1 + S2-reactive SIgA/IgA and SIgM/IgM, as well as HCoV-OC43 S1 + S2-reactive IgG were related to the symptoms. The duration of antibody levels in human milk in mothers with viral symptoms varied between 3 and 4 months post maternal report of viral symptoms.

Conclusion: Previous viral symptoms and individual mothers may change the antibody cross-reactive levels to SARS-CoV-2 and HCoVs in human milk.

Family-centered care (FCC) has become the normative practice in Neonatal ICUs across North America. Over the past 25 years, it has grown to impact clinician-parent collaborations broadly within children’s hospitals as well as in the NICU and shaped their very culture. In the current COVID-19 pandemic, the gains made over the past decades have been challenged by “visitor” policies that have been implemented, making it difficult in many instances for more than one parent to be present and truly incorporated as members of their baby’s team. Difficult access, interrupted bonding, and confusing messaging and information about what to expect for their newborn can still cause them stress. Similarly, NICU staff have experienced moral distress. In this perspective piece, we review those characteristics of FCC that have been disrupted or lost, and the many facets of rebuilding that are presently required.

In utero transmission of severe acute respiratory syndrome coronavirus 2 infection is a point of debate. We report a case of severe acute respiratory syndrome coronavirus 2 vertical transmission from asymptomatic mother, with molecular detection in mother’s blood at delivery and neonatal nasopharyngeal swabs at 5 and 28 hours of life and later IgG seroconversion. The newborn was asymptomatic.

Background: As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants.

Methods: Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18-54 years) and older adults (aged 55-75 years). Participants were randomly allocated either vaccine or placebo using a list prepared by the study funder. Participants were to receive two doses of SCB-2019 (either 3 μg, 9 μg, or 30 μg) or a placebo (0·9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. The assigned treatment was administered in opaque syringes to maintain masking of assignments. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by ELISA and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. This trial is registered with ClinicalTrials.gov, NCT04405908; this is an interim analysis and the study is continuing.

Findings: Between June 19 and Sept 23, 2020, 151 volunteers were enrolled; three people withdrew, two for personal reasons and one with an unrelated serious adverse event (pituitary adenoma). 148 participants had at least 4 weeks of follow-up after dose two and were included in this analysis (database lock, Oct 23, 2020). Vaccination was well tolerated, with two grade 3 solicited adverse events (pain in 9 μg AS03-adjuvanted and 9 μg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44-69%) than with those containing CpG/Alum adjuvant (6-44%) or no adjuvant (3-13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titres at day 36 were 1567-4452 with AS03 and 174-2440 with CpG/Alum). Titres in all AS03 dose groups and the CpG/Alum 30 μg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses.

Interpretation: The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralising activity. Both adjuvanted vaccine formulations were well tolerated and are suitable for further clinical development.

Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.

Methods: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).

Interpretation: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.

Objective: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.

Design: Observational cohort study.

Setting: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.

Participants: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.

Main outcome measures: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.

Results: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.

Conclusions: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

Background: A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial.

Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial at 25 hospitals and polyclinics in Moscow, Russia. We included participants aged at least 18 years, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the 14 days before enrolment, and no other vaccinations in the 30 days before enrolment. Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group. Investigators, participants, and all study staff were masked to group assignment. The vaccine was administered (0·5 mL/dose) intramuscularly in a prime-boost regimen: a 21-day interval between the first dose (rAd26) and the second dose (rAd5), both vectors carrying the gene for the full-length SARS-CoV-2 glycoprotein S. The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose. All analyses excluded participants with protocol violations: the primary outcome was assessed in participants who had received two doses of vaccine or placebo, serious adverse events were assessed in all participants who had received at least one dose at the time of database lock, and rare adverse events were assessed in all participants who had received two doses and for whom all available data were verified in the case report form at the time of database lock. The trial is registered at ClinicalTrials.gov (NCT04530396).

Findings: Between Sept 7 and Nov 24, 2020, 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476). 19 866 received two doses of vaccine or placebo and were included in the primary outcome analysis. From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14 964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6-95·2). Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events). 45 (0·3%) of 16 427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee. Four deaths were reported during the study (three [<0·1%] of 16 427 participants in the vaccine group and one [<0·1%] of 5435 participants in the placebo group), none of which were considered related to the vaccine.

Interpretation: This interim analysis of the phase 3 trial of Gam-COVID-Vac showed 91·6% efficacy against COVID-19 and was well tolerated in a large cohort.

Background: Remdesivir is being studied and used for treatment of coronavirus disease 2019 (COVID-19).

Purpose: To update a previous review of remdesivir for adults with COVID-19, including new meta-analyses of patients with COVID-19 of any severity compared with control.

Data sources: Several sources from 1 January 2020 through 7 December 2020.

Study selection: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. New evidence is incorporated by using living review methods.

Data extraction: 1 reviewer abstracted data; a second reviewer verified the data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.

Data synthesis: The update includes 5 RCTs, incorporating data from a new large RCT and the final results of a previous RCT. Compared with control, a 10-day course of remdesivir probably results in little to no reduction in mortality (risk ratio [RR], 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) but may result in a small reduction in the proportion of patients receiving mechanical ventilation (RR, 0.71 [CI, 0.56 to 0.90]; 3 RCTs). Remdesivir probably results in a moderate increase in the percentage of patients who recovered and a moderate decrease in serious adverse events and may result in a large reduction in time to recovery. Effect on hospital length of stay or percentage remaining hospitalized is mixed. Compared with a 10-day course for those not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved.

Limitation: Summarizing findings was challenging because of varying disease severity definitions and outcomes.

Conclusion: In hospitalized adults with COVID-19, remdesivir probably results in little to no mortality difference but probably improves the percentage recovered and reduces serious harms and may result in a small reduction in the proportion receiving ventilation. For patients not receiving ventilation, a 5-day course may provide greater benefits and fewer harms with lower drug costs than a 10-day course.

Importance: Convalescent plasma is a proposed treatment for COVID-19.

Objective: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).

Data sources: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021.

Study selection: The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting.

Data extraction and synthesis: Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Main outcomes and measures: All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events.

Results: A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was -1.21% (95% CI, -5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was -2.56% [95% CI, -13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences.

Conclusions and relevance: Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

Current diagnostic standards involve SARS-CoV-2 detection in nasopharyngeal swabs (NPS), but saliva is an attractive and non-invasive option for diagnosis. The objectives were to determine the performance of saliva in comparison to NPS for detecting SARS-CoV-2 and to compare the optimized home brew RT-PCR with a commercial RT-PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT-PCR from patients presenting at an emergency room with signs and symptoms compatible with COVID-19. A total of 348 samples from 174 patients were tested by RT-PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS-CoV-2 positive in NPS using the optimized home-brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS-CoV-2 saliva was detected in a patient with pneumonia. Kappa Cohen’s coefficient agreement between NPS and saliva was 0.96 (95%CI 0.90-0.99). Median Ct values in NPS versus saliva were 18.88 (IQR 15.60-23.58; Range: 11.97-38.10) versus 26.10 (IQR 22.75-30.06; Range: 13.78-39.22), respectively (p < 0.0001). The optimized home-brew RT-PCR demonstrated higher analytical and clinical sensitivity compared to the commercial RT-PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home-brew PCR even when the viral load in saliva was lower than in NPS. This non-invasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self-collection of saliva can diminish exposure to healthcare personnel.

The preterm birth rate was unchanged in a metropolitan U.S. hospital system during the peak of the coronavirus disease 2019 (COVID-19) pandemic compared with the prior year.

The coronavirus disease 2019 (COVID-19), which had spread to the world from Wuhan (China) in late December, was announced as a pandemic by the World Health Organization in March 2020. In addition to acute respiratory syndrome symptoms, this virus also affects nonrespiratory organs, according to existing data. ACE2 and TMPRSS2, which play a critical role in the entrance of SARS-COV-2 into the cell, are coexpressed in placental development stages, so the placenta also carries a risk for this virus. Many studies have shown that this virus causes some histopathological changes in the placenta. The vertical transmission of the virus is not yet clear, but available data have shown that the indirect effects of the virus can be seen on the fetus. This article focuses on revealing the effects of the virus on the placenta in all aspects.

COVID-19, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), affects people of all ages. The virus can cause multiple systemic infections, principally in the respiratory tract, as well as microvascular damage. Ocular manifestations of COVID-19 are uncommon in adults and children. We describe ophthalmic manifestations in newborns detected by slit-lamp examination, fundus examination, and fluorescein angiography. All patients showed edema and hemorrhagic conjunctivitis; fundus examinations revealed cotton wool spots and vitreous hemorrhage, and microvascular damage manifested as patchy choroidal filling, peripapillary hyperfluorescence, delayed retinal filling and venous laminar flow, and boxcarring on fluorescein angiography.

Background: A population-based study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes.

Methods: Prospective, population-based study including pregnant women consecutively attended at first/second trimester or at delivery at three hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (IgG and IgM/IgA) were measured in all participants and nasopharyngeal RT-PCR was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2 positive versus negative women: miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational age, neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women.

Results: Of 2,225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n=314, 99.1%) and/or RT-PCR (n=36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild COVID-19 and 7 (2.2%) pneumonia, of which 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively [risk difference -0.4%, (95% CI: -4.1% to 4.1)]. As compared with non-infected women, women with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs. 16.9%, p=0.003) and intrapartum fetal distress (9.1% vs. 19.2%, p=0.004), while asymptomatic women had similar rates to non-infected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood.

Conclusions: The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to non-infected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.

Preliminary data in Europe have suggested a reduction in prematurity rates during the COVID-19 pandemic, implying that contingency measures could have an impact on prematurity rates. We designed a population-based prevalence proportion study to explore the potential link between national lockdown measures and a change in preterm births and stillbirths. Adjusted multivariate analyses did not show any decrease in preterm proportions during the lockdown period with respect to the whole prelockdown period or to the prelockdown comparison periods (2015-2019): 6.5% (95%CI 5.6-7.4), 6.6% (95%CI 6.5-6.8), and 6.2% (95%CI 5.7-6.7), respectively. Proportions of preterm live births did not change during lockdown when different gestational age categories were analyzed, nor when birthweight categories were considered. No differences in stillbirth rates among the different study periods were found: 0.33% (95%CI 0.04-0.61) during the lockdown period vs. 0.34% (95%CI 0.22-0.46) during the prelockdown comparison period (2015-2019).Conclusion: We did not find any link between prematurity and lockdown, nor between stillbirths and lockdown. Collaborative efforts are desirable to gather more data and additional evidence on this global health issue. What is Known: • Prematurity is associated with increased risk of morbidity and mortality. • Contingency measures during the COVID-19 pandemic may have an impact on reducing prematurity rates. What is New: • Prematurity and stillbirth rates remained stable in Castilla-y-León, a Spanish region, during COVID-19 lockdown. • The role of behavioral patterns and sociocultural factors in the prevention of preterm birth as a result of lockdown measures remains a subject for debate.