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Tratamento e acompanhamento de doenças raras em tempos de COVID-19

with Tiago Rama ‚Äď MD (Centro Hospitalar de S.Jo√£o), Jo√£o Cabrita ‚Äď Fisioterapeuta (APELA), Filomena Borges ‚Äď Respons√°vel Comunica√ß√£o (APELA)

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Muthiah Vaduganathan

‚ÄĘ march 2020

Renin‚ÄďAngiotensin‚ÄďAldosterone System Inhibitors in Patients with Covid-19

Os autores sugerem os seguintes pontos-chave da rela√ß√£o entre Covid19 e o Sistema Renina-Angiotensina-Aldosterona:- ACE2, uma enzima que contraria fisiologicamente a ativa√ß√£o do RAAS, √© o receptor funcional do SARS-CoV-2, o v√≠rus respons√°vel pela pandemia de Covid-19- Estudos pr√©-cl√≠nicos selecionados sugeriram que os inibidores do RAAS podem aumentar a express√£o da ACE2, levantando preocupa√ß√Ķes sobre a seguran√ßa em pacientes com Covid-19- Dados insuficientes est√£o dispon√≠veis para determinar se essas observa√ß√Ķes se traduzem prontamente em seres humanos e nenhum estudo avaliou os efeitos dos inibidores do RAAS no Covid-19- Ensaios cl√≠nicos est√£o em andamento para testar a seguran√ßa e efic√°cia dos moduladores de RAAS, incluindo a combina√ß√£o ACE2 humano e losartan ARB em Covid-19- A retirada abrupta de inibidores do RAAS em pacientes de alto risco, incluindo aqueles com insufici√™ncia card√≠aca ou enfarte do mioc√°rdio, pode resultar em instabilidade cl√≠nica e resultados adversos √† sa√ļde- At√© que dados adicionais estejam dispon√≠veis, acreditamos que os inibidores do RAAS devem ser continuados em pacientes em condi√ß√Ķes est√°veis que correm risco, sendo suspeitos ou confirmados com Covid-19

New England Journal of Medicine

Bin Cao

‚ÄĘ march 2020

A Trial of Lopinavir‚ÄďRitonavir 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‚Äďritonavir (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‚Äďritonavir group, and 100 to the standard-care group. Treatment with lopinavir‚Äďritonavir 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‚Äďritonavir group and the standard-care group (19.2% vs. 25.0%; difference, ‚ąí5.8 percentage points; 95% CI, ‚ąí17.3 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‚Äďritonavir 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‚Äďritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir‚Äďritonavir 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‚Äďritonavir 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

‚ÄĘ 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 őľm) 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.

‚ÄĘ march 2020

Hydroxychloroquine and azithromycin as a treatment of COVID‚Äź19: results of an open‚Äźlabel non‚Äź 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

António Pedro Machado

‚ÄĘ 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 seguran√ßa dos IECA e ARA II foi questionada em dois artigos de opini√£o, tendo os autores sugerido que os doentes sob tratamento com estes f√°rmacos poderiam estar sujeitos a uma evolu√ß√£o mais grave da doen√ßa, em caso de infec√ß√£o pelo coronav√≠rus 1,2. Na origem destas preocupa√ß√Ķes h√° raz√Ķes te√≥ricas leg√≠timas apoiadas em dados epidemiol√≥gicos; no conhecimento dispon√≠vel dos mecanismos patog√©nicos da infec√ß√£o pelos coronav√≠rus; na resposta inflamat√≥ria do hospedeiro √†s infec√ß√Ķes e das complexas vias de sinaliza√ß√£o envolvidas; e no mecanismo de ac√ß√£o dos IECA e ARA II. Algumas das extrapola√ß√Ķes publicadas baseiam-se em resultados de estudos que mostraram, entre os doentes com o COVID-19, ser a preval√™ncia de hipertens√£o (HTA) mais elevada nos que desenvolveram doen√ßa grave, incluindo ARDS e morte, do que nos que tiveram uma evolu√ß√£o mais favor√°vel3,4. Por√©m, √† excep√ß√£o de um estudo com 191 casos5, n√£o foram feitas an√°lises ajustadas dos resultados, raz√£o por que os estudos n√£o permitem, com seguran√ßa, associar o pior progn√≥stico dos doentes √† presen√ßa de HTA, cuja preval√™ncia variou entre 23,7% e 58%3-5. Apesar de o tratamento anti-hipertensivo pr√©vio n√£o ter sido avaliado em qualquer dos estudos em causa3-5 , os autores procuraram estabelecer uma rela√ß√£o de causalidade entre a terap√™utica anti-hipertensiva e o pior progn√≥stico observado nos hipertensos infectados pelo COVID-19. Dado os bloqueadores do Sistema Renina-Angiotensina-Aldosterona (SRAA) - IECA e ARA II serem dos f√°rmacos mais utilizados no tratamento da HTA, admitiram aqueles autores que estes f√°rmacos poderiam ter tido um efeito facilitador da invas√£o viral e das suas complica√ß√Ķes1, notavelmente a ARDS6. N√£o foi considerada a hip√≥tese alternativa de a hiperactividade do SRRA, presente nos hipertensos e agravada pelo SARS-CoV, ser um dos determinantes major da amplifica√ß√£o do processo inflamat√≥rio desencadeado pelo hospedeiro em resposta √† invas√£o viral. Acontece que na China, onde 37% da popula√ß√£o entre os 37 e os 75 anos √© hipertensa e 44% das mortes s√£o atribu√≠das √†s doen√ßas cardiovasculares, apenas 23% dos hipertensos est√£o sob tratamento anti-hipertensivo7. Como a taxa de prescri√ß√£o dos ARAII /IECA na China √© inferior a 7.5%7 e porque a associa√ß√£o das duas classes n√£o est√° recomendada, dos mais de 250 milh√Ķes de hipertensos existentes, menos de 4,5 milh√Ķes estar√£o em tratamento com um ARA II ou IECA7. Desta forma, pela for√ßa dos n√ļmeros, n√£o √© poss√≠vel estabelecer-se uma rela√ß√£o de causalidade entre o pior progn√≥stico observado nos hipertensos com infec√ß√£o pelo COVID-19 e o tratamento com ARA II ou IECA.

Sociedade Portuguesa de Cardiologia

Chaomin Wu

‚ÄĘ 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 (‚Č•39 ¬įC) 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

‚ÄĘ 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 (‚Č•39 ¬įC) 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

Giacomo Grasselli

‚ÄĘ march 2020

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy

On February 20, 2020, a patient in his 30s admitted to the intensive care unit (ICU) in Codogno Hospital (Lodi, Lombardy, Italy) tested positive for a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). He had a history of atypical pneumonia that was not responding to treatment, but he was not considered at risk for COVID-19 infection. The positive result was immediately reported to the Lombardy health care system and governmental offices. During the next 24 hours, the number of reported positive cases increased to 36. This situation was considered a serious development for several reasons: the patient (‚Äúpatient 1‚ÄĚ) was healthy and young; in less than 24 hours, 36 additional cases were identified, without links to patient 1 or previously identified positive cases already in the country; it was not possible to identify with certainty the source of transmission to patient 1 at the time; and, because patient 1 was in the ICU and there were already 36 cases by day 2, chances were that a cluster of unknown magnitude was present and additional spread was likely. On February 21, an emergency task force was formed by the Government of Lombardy and local health authorities to lead the response to the outbreak. This Viewpoint provides a summary of the response of the COVID-19 Lombardy ICU network and a forecast of estimated ICU demand over the coming weeks (projected to March 20, 2020).

Jama Network

Lauer, Stephen A.

‚ÄĘ 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

Joshua M. Sharfstein

‚ÄĘ 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‚Äôs 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 ‚Äúsubject to doctors‚Äô orders, any American can be tested.‚ÄĚ 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

Dong Y

‚ÄĘ 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

‚ÄĘ 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

‚ÄĘ february 2020

Combination of RT‚ÄźqPCR testing and clinical features for diagnosis of COVID‚Äź19 facilitates management of SARS‚ÄźCoV‚Äź2 outbreak

Quantitative real‚Äźtime reverse transcriptase‚Äźpolymerase chain reaction (RT‚ÄźqPCR) assay has routinely been used for the detection of causative viruses from respiratory secretions and final pathogenic diagnostics of COVID‚Äź19. More than seven types of SARS‚ÄźCoV‚Äź2 nucleic acid test kit have been developed and approved rapidly, while a large number of the ‚Äúsuspected‚ÄĚ cases with typical clinical COVID‚Äź19 features and identical specific computed tomography (CT) images were not diagnosed. Unfortunately, due to an overwhelming situation in local hospitals, many ‚Äúsuspected‚ÄĚ cases and diagnosed cases cannot efficiently be separated or treated. Recently, one patient was not confirmed by RT‚ÄźqPCR testing for SARS‚ÄźCoV‚Äź2 infection for the first three times within 3 weeks before bronchoalveolar lavage fluid (BALF) was acquired, results from both RT‚ÄźqPCR and next‚Äźgeneration sequencing (NGS) testing were positive for SRAS‚ÄźCoV‚Äź2. These largely affected efficiency to control viral spreading and outbreak. Indeed, several factors have been proposed to explain the inconsistency or the high false‚Äźnegative rate (FNR). For example, results from RT‚ÄźqPCR 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‚Äźtime testing was as high as 30% to 50% in real COVID‚Äź19 cases.

Journal of Medical Virology

Huijun Chen

‚ÄĘ 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√ó10‚ĀĻ 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‚Äď9 and a 5-min Apgar score of 9‚Äď10. 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

‚ÄĘ 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

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