Nights against COVID-19

Debate about COVID-19 in a webinar format

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Recent COVID-19

Dan Sun

• march, 2020

Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study

Background: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19.\n\n Methods: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children’s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19.\n\n Results: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-γ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home.\n\n Conclusions: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.

World Journal of Pediatrics

Bin Cao

• march, 2020

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit.

New England Journal of Medicine

van Doremalen

• march, 2020

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates.

New England Journal of Medicine

Gautret et al.

• march, 2020

Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐ randomized clinical trial.

Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

International Journal of Antimicrobial Agents

Neil M Ferguson

• march, 2020

Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand

The global impact of COVID-19 has been profound, and the public health threat it represents is the absenteeism. The major challenge of suppression is that this type of intensive intervention package –or something equivalently effective at reducing transmission – will need to be maintained until avaccine becomes available (potentially 18 months or more) – given that we predict that transmissionwill quickly rebound if interventions are relaxed. We show that intermittent social distancing –triggered by trends in disease surveillance – may allow interventions to be relaxed temporarily inrelative short time windows, but measures will need to be reintroduced if or when case numbersrebound. Last, while experience in China and now South Korea show that suppression is possible inthe short term, it remains to be seen whether it is possible long-term, and whether the social andeconomic costs of the interventions adopted thus far can be reduced.most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present theresults of epidemiological modelling which has informed policymaking in the UK and other countriesin recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number ofpublic health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducingcontact rates in the population and thereby reducing transmission of the virus. In the results presentedhere, we apply a previously published microsimulation model to two countries: the UK (Great Britainspecifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likelyto be limited, requiring multiple interventions to be combined to have a substantial impact ontransmission. Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarilystopping epidemic spread – reducing peak healthcare demand while protecting those most at risk ofsevere disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducingcase numbers to low levels and maintaining that situation indefinitely. Each policy has majorchallenges. We find that that optimal mitigation policies (combining home isolation of suspect cases,home quarantine of those living in the same household as suspect cases, and social distancing of theelderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 anddeaths by half. However, the resulting mitigated epidemic would still likely result in hundreds ofthousands of deaths and health systems (most notably intensive care units) being overwhelmed manytimes over. For countries able to achieve it, this leaves suppression as the preferred policy option.We show that in the UK and US context, suppression will minimally require a combination of socialdistancing of the entire population, home isolation of cases and household quarantine of their familymembers. This may need to be supplemented by school and university closures, though it should berecognised that such closures may have negative impacts on health systems due to increased

Imperial College London

António Pedro Machado

• march, 2020

Posição da Sociedade Portuguesa de Cardiologia sobre a utilização de IECA e ARA II no contexto da pandemia do COVID-19

No contexto da actual pandemia, a segurança dos IECA e ARA II foi questionada em dois artigos de opinião, tendo os autores sugerido que os doentes sob tratamento com estes fármacos poderiam estar sujeitos a uma evolução mais grave da doença, em caso de infecção pelo coronavírus 1,2. Na origem destas preocupações há razões teóricas legítimas apoiadas em dados epidemiológicos; no conhecimento disponível dos mecanismos patogénicos da infecção pelos coronavírus; na resposta inflamatória do hospedeiro às infecções e das complexas vias de sinalização envolvidas; e no mecanismo de acção dos IECA e ARA II. Algumas das extrapolações publicadas baseiam-se em resultados de estudos que mostraram, entre os doentes com o COVID-19, ser a prevalência de hipertensão (HTA) mais elevada nos que desenvolveram doença grave, incluindo ARDS e morte, do que nos que tiveram uma evolução mais favorável3,4. Porém, à excepção de um estudo com 191 casos5, não foram feitas análises ajustadas dos resultados, razão por que os estudos não permitem, com segurança, associar o pior prognóstico dos doentes à presença de HTA, cuja prevalência variou entre 23,7% e 58%3-5. Apesar de o tratamento anti-hipertensivo prévio não ter sido avaliado em qualquer dos estudos em causa3-5 , os autores procuraram estabelecer uma relação de causalidade entre a terapêutica anti-hipertensiva e o pior prognóstico observado nos hipertensos infectados pelo COVID-19. Dado os bloqueadores do Sistema Renina-Angiotensina-Aldosterona (SRAA) - IECA e ARA II serem dos fármacos mais utilizados no tratamento da HTA, admitiram aqueles autores que estes fármacos poderiam ter tido um efeito facilitador da invasão viral e das suas complicações1, notavelmente a ARDS6. Não foi considerada a hipótese alternativa de a hiperactividade do SRRA, presente nos hipertensos e agravada pelo SARS-CoV, ser um dos determinantes major da amplificação do processo inflamatório desencadeado pelo hospedeiro em resposta à invasão viral. Acontece que na China, onde 37% da população entre os 37 e os 75 anos é hipertensa e 44% das mortes são atribuídas às doenças cardiovasculares, apenas 23% dos hipertensos estão sob tratamento anti-hipertensivo7. Como a taxa de prescrição dos ARAII /IECA na China é inferior a 7.5%7 e porque a associação das duas classes não está recomendada, dos mais de 250 milhões de hipertensos existentes, menos de 4,5 milhões estarão em tratamento com um ARA II ou IECA7. Desta forma, pela força dos números, não é possível estabelecer-se uma relação de causalidade entre o pior prognóstico observado nos hipertensos com infecção pelo COVID-19 e o tratamento com ARA II ou IECA.

Sociedade Portuguesa de Cardiologia

Chaomin Wu

• march, 2020

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures: Confirmed COVID-19 pneumonia.Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Jama Network

Chaomin Wu

• march, 2020

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Jama Network

Fei Zhou

• march, 2020

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Background: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.\n\n Methods: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.\n\n Findings: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.

The Lancet

Lauer, Stephen A.

• march, 2020

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases.

Annals of Internal Medicine

E. Mullins

• march, 2020

Coronavirus in pregnancy and delivery: rapid review

OBJECTIVES: Person-to-person spread of COVID-19 in the UK has now been confirmed. There are limited case series reporting the impact on women affected by coronaviruses (CoV) during pregnancy. In women affected by SARS and MERS, the case fatality rate appeared higher in women affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the RCOG guidelines on COVID-19 infection in pregnancy.\n\n METHODS: Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomised controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the RCPCH and RCOG who provided expert consensus on areas in which data were lacking.\n\n RESULTS: From 9965 results in PubMed and 600 in MedRxiv, 23 relevant studies (case reports and case series) were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU) (one of whom remained on extracorporeal membrane oxygenation). No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with RT-PCR after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester.\n\n CONCLUSIONS: Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and one woman who remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK’s reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, the RCOG (in consultation with the RCPCH) developed guidance for delivery and neonatal care which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of COVID-19-affected mothers and babies. We hope this review will be helpful for maternity and neonatal services planning their response to COVID-19.

Ultrasound in Obstetrics and Gynecology

Joshua M. Sharfstein

• march, 2020

Diagnostic Testing for the Novel Coronavirus

Controversies over diagnostic testing have dominated US headlines about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease 2019 (COVID-19). Technical challenges with the first test developed by the Centers for Disease Control and Prevention (CDC) left the nation with minimal diagnostic capacity during the first few weeks of the epidemic. The CDC also initially limited access to testing to a narrow group of individuals with known exposure. The delayed discovery of a case of COVID-19 in California, followed quickly by evidence of community transmission in multiple states, revealed the shortcomings of this strategy. In the early stages, COVID-19 has spread beyond the nation’s ability to detect it. On February 29, the US Food and Drug Administration (FDA) moved to expand testing capacity by eliminating a requirement that advanced laboratories obtain prior FDA authorization before using their own, laboratory-developed tests. Then, on March 3, Vice President Pence announced the removal of all federal limits on testing, stating that “subject to doctors’ orders, any American can be tested.” These steps left many with questions about what had happened with testing and what should happen next. Unraveling this situation requires understanding how the regulatory structure for diagnostic tests interacts with public health emergencies. It also involves appreciating the distinction between testing capacity for public health surveillance and clinical care. While the public may want extensive testing, the usefulness of testing is greater in some scenarios than others. It is important to balance 2 concepts: remedying testing gaps is imperative, yet more testing is not always better.

Jama Network

Jasper Fuk-Woo Chan

• march, 2020

Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-polymerase chain reaction assay validated in vitro and with clinical specimens

On 31st December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated Coronavirus Disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time RT-PCR assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 TCID50/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRd-P2-negative specimens [119/273 (43.6%) vs 77/273 (28.2%), P<0.001], including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21×104 RNA copies/ml (range, 2.21×102 to 4.71×105 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.

Journal of Clinical Microbiology

Dong Y

• march, 2020

Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China

OBJECTIVES: To identify the epidemiological characteristics and transmission patterns ofpediatric patients with COVID-19 in China.METHODS: Nationwide case series of 2143 pediatric patients with COVID-19 reported to theChinese Center for Disease Control and Prevention from January 16 to February 8, 2020 wereincluded. The epidemic curves were constructed by key dates of disease onset and case diagnosis.Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on bothonset and diagnosis dates.RESULTS: There were 731 (34.1%) laboratory-confirmed cases and 1412 (65.9%) suspectedcases. The median age of all patients was 7 years (interquartile range: 2-13), and 1213 cases(56.6%) were boys. Over 90% of all patients were asymptomatic, mild, or moderate cases. Themedian time from illness onset to diagnoses was 2 days (range: 0 to 42 days). There was a rapidincrease of disease at the early stage of the epidemic and then there was a gradual and steadydecrease. Disease rapidly spread from Hubei Province to surrounding provinces over time. Morechildren were infected in Hubei province than any other province.CONCLUSIONS: Children at all ages appeared susceptible to COVID-19, and there was nosignificant gender difference. Although clinical manifestations of children’s COVID-19 caseswere generally less severe than those of adults’ patients, young children, particularly infants, werevulnerable to infection. The distribution of children’s COVID-19 cases varied with time and space,and most of the cases concentrated in Hubei province and surrounding

Pediatrics

Sana Salehi

• february, 2020

Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients

OBJECTIVE. Available information on CT features of the 2019 novel coronavirus disease (COVID-19) is scattered in different publications, and a cohesive literature review has yet to be compiled. MATERIALS AND METHODS. This article includes a systematic literature search of PubMed, Embase (Elsevier), Google Scholar, and the World Health Organization database. RESULTS. Known features of COVID-19 on initial CT include bilateral multilobar ground-glass opacification (GGO) with a peripheral or posterior distribution, mainly in the lower lobes and less frequently within the right middle lobe. Atypical initial imaging presentation of consolidative opacities superimposed on GGO may be found in a smaller number of cases, mainly in the elderly population. Septal thickening, bronchiectasis, pleural thickening, and subpleural involvement are some of the less common findings, mainly in the later stages of the disease. Pleural effusion, pericardial effusion, lymphadenopathy, cavitation, CT halo sign, and pneumothorax are uncommon but may be seen with disease progression. Follow-up CT in the intermediate stage of disease shows an increase in the number and size of GGOs and progressive transformation of GGO into multifocal consolidative opacities, septal thickening, and development of a crazy paving pattern, with the greatest severity of CT findings visible around day 10 after the symptom onset. Acute respiratory distress syndrome is the most common indication for transferring patients with COVID-19 to the ICU and the major cause of death in this patient population. Imaging patterns corresponding to clinical improvement usually occur after week 2 of the disease and include gradual resolution of consolidative opacities and decrease in the number of lesions and involved lobes. CONCLUSION. This systematic review of current literature on COVID-19 provides insight into the initial and follow-up CT characteristics of the disease. Read More: https://www.ajronline.org/doi/abs/10.2214/AJR.20.23034

American Journal of Roentgenology

Yishan Wang

• february, 2020

Combination of RT‐qPCR testing and clinical features for diagnosis of COVID‐19 facilitates management of SARS‐CoV‐2 outbreak

Quantitative real‐time reverse transcriptase‐polymerase chain reaction (RT‐qPCR) assay has routinely been used for the detection of causative viruses from respiratory secretions and final pathogenic diagnostics of COVID‐19. More than seven types of SARS‐CoV‐2 nucleic acid test kit have been developed and approved rapidly, while a large number of the “suspected” cases with typical clinical COVID‐19 features and identical specific computed tomography (CT) images were not diagnosed. Unfortunately, due to an overwhelming situation in local hospitals, many “suspected” cases and diagnosed cases cannot efficiently be separated or treated. Recently, one patient was not confirmed by RT‐qPCR testing for SARS‐CoV‐2 infection for the first three times within 3 weeks before bronchoalveolar lavage fluid (BALF) was acquired, results from both RT‐qPCR and next‐generation sequencing (NGS) testing were positive for SRAS‐CoV‐2. These largely affected efficiency to control viral spreading and outbreak. Indeed, several factors have been proposed to explain the inconsistency or the high false‐negative rate (FNR). For example, results from RT‐qPCR testing using primers in the ORF1ab gene and N genes can be affected by the variation of viral RNA sequences. In terms of the natural history of the disease and viral load in different anatomic sites of the patients, sampling procedures largely contribute to high FNR. By estimate, FNR from one‐time testing was as high as 30% to 50% in real COVID‐19 cases.

Journal of Medical Virology

Huijun Chen

• february, 2020

Clinical Characteristics and Intrauterine Vertical Transmission Potential of COVID-19 Infection in Nine Pregnant Women: A Retrospective Review of Medical Records

Background: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0×10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.

The Lancet

Huaping Zhu

• february, 2020

Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia

Background: The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019-nCoV infections in neonates. Methods: The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. Results: Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. Conclusions: Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.

Translational Pediatrics

Leslie A. Nickell

• march, 2004

Psychosocial effects of SARS on hospital staff: survey of a large tertiary care institution

Background: The outbreak of SARS in 2003 had a dramatic effect on the health care system in Toronto. The main objective of this study was to investigate the psychosocial effects associated with working in a hospital environment during this outbreak.\n\n Methods: Questionnaires were distributed to all willing employees of Sunnybrook and Women's College Health Sciences Centre between Apr. 10 and 22, 2003. The survey included questions regarding concern about SARS, precautionary measures, personal well-being and sociodemographic characteristics; a subsample also received the 12-item version of the General Health Questionnaire (GHQ-12).\n\n Results: Of the 4283 questionnaires distributed, 2001 (47%) were returned, representing 27% of the total hospital employee population of 7474. The proportions of respondents who were allied health care professionals, nurses and doctors and who worked in areas other than patient care were representative of the hospital staff population as a whole. Of the 2001 questionnaires, 510 contained the GHQ-12. Two-thirds of the respondents reported SARS-related concern for their own or their family's health. A total of 148 respondents (29%) scored above the threshold point on the GHQ-12, indicating probable emotional distress; the rate among nurses was 45%. Masks were reported to be the most bothersome infection control precaution. Logistic regression analysis identified 4 factors as being significantly associated with increased levels of concern for personal or family health: perception of a greater risk of death from SARS (adjusted odds ratio [OR] 5.0, 95% confidence interval [CI] 2.6–9.6), living with children (adjusted OR 1.8, 95% CI 1.5–2.3), personal or family lifestyle affected by SARS outbreak (adjusted OR 3.3, 95% CI 2.5–4.3) and being treated differently by people because of working in a hospital (adjusted OR 1.6, 95% CI 1.2–2.1). Four factors were identified as being significantly associated with the presence of emotional distress: being a nurse (adjusted OR 2.8, 95% CI 1.5–5.5), part-time employment status (adjusted OR 2.6, 95% CI 1.2–5.4), lifestyle affected by SARS outbreak (adjusted OR 2.2, 95% CI 1.4–3.5) and ability to do one's job affected by the precautionary measures (adjusted OR 2.9, 95% CI 1.9–4.6).\n\n Interpretation: Our findings indicate that the SARS outbreak had significant psychosocial effects on hospital staff. These effects differed with respect to occupation and risk perception. The effect on families and lifestyle was also substantial. These findings highlight the need for interventions to address psychosocial distress and concern and to provide support for employees during such crises.

CMAJ

Nights against COVID-19

Debate about COVID-19 in a webinar format

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