Mês: março 2020

#Nova estratégia contra a dor crónica inflamatória

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Fonte de imagem: New Atlas

Num estudo da Universidade de Medicina Charité de Berlim desenvolveu-se um novo método contra a dor e inflamação crónica.

Inflamação no nervo periférico pode levar a dor crónica. A resposta inflamatória é mediada por células imunitárias derivadas do sangue que produzem citoquinas que irão aumentar ou reduzir a dor e inflamação.

Graças às suas propriedades anti-inflamatórias, as citoquinas interleuquina-4 (IL-4) incitam à produção de opiáceos endógenos por parte de células sanguíneas no local da inflamação, reduzindo a dor.

Para analisar este mecanismo, os cientistas usaram modelos animais com dor ciática. Uma só injeção de IL-4 perto do nervo inflamado aliviou a dor durante alguns minutos.

Quando repetida diariamente, a injeção reduziu a dor durante 8 dias, mesmo depois de parado o tratamento.

Este método levou a que a IL-4 induzisse a acumulação de macrófagos M2, um tipo de células imunitárias que produzem opiáceos, consequentemente reduzindo a dor.

Estes macrófagos foram depois transplantados noutro animal a quem reduziram a dor de igual forma no nervo inflamado. Uma análise mais profunda e isolada revelou que estas células produziram os opiáceos endorfina, encefalina e dinorfina.

Esta descoberta oferece novas perspetivas de tratamento contra a dor e inflamação crónica.


#Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies

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Coronavirus Travel Advice – How to Avoid Covid-19 while Travelling


Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China. [1It was initially reported to the World Health Organization (WHO) on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency. [23On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring H1N1 influenza a pandemic in 2009. [4]

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process. Gordon et al identified 332 high-confidence SARS-CoV-2 human protein-protein interactions. Among these, they identified 66 human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials, and/or preclinical compounds. As of March 22, 2020, these researchers are in the process of evaluating the potential efficacy of these drugs in live SARS-CoV-2 infection assays. [5]

McCreary and Pogue’s “Review of Early and Emerging Options” for COVID-19 treatment provides a comprehensive review of potential beneficial therapies and adjunctive treatments. [6]

An international collaborative publication offers guidance for sepsis management in critically ill adults with COVID-19 and includes evidence-based recommendations.


Updated: Mar 27, 2020
  • Author: Scott J Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP;

#Coronaviruses and Acute Respiratory Syndromes (COVID-19, MERS, and SARS)

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Coronavirus Travel Advice – How to Avoid Covid-19 while Travelling
Coronaviruses are a large family of viruses that cause respiratory illness ranging in severity from the common cold to fatal pneumonia.

There are many different coronaviruses. Most of them cause illness in animals. However, 7 types of coronaviruses are known to cause illness in humans.

Four of these 7 human coronavirus infections involve mild upper respiratory tract illness that causes symptoms of the common cold.

However, 3 of the 7 human coronavirus infections can be much more severe and have recently caused major outbreaks of deadly pneumonia:

  • SARS-CoV2 is a novel coronavirus that was first identified in Wuhan, China in late 2019 as the cause of coronavirus disease 2019 (COVID-19) and spread worldwide.

  • MERS-CoV was identified in 2012 as the cause of Middle East respiratory syndrome (MERS).

  • SARS-CoV was identified in 2002 as the cause of an outbreak of severe acute respiratory syndrome (SARS).

These coronaviruses that cause severe respiratory infections are transmitted from animals to humans (zoonotic pathogens).


COVID-19 is an acute respiratory illness that can be severe and is caused by a newly identified coronavirus officially named SARS-CoV2.

COVID-19 was first reported in late 2019 in Wuhan, China and has since spread extensively in China and worldwide. For current information on the number of cases and deaths, see the Centers for Disease Control and Prevention: 2019 Novel Coronavirus and the World Health Organization’s Novel Coronavirus (COVID-2019) situation reports.

Early COVID-19 infections were linked to a live animal market in Wuhan, China, suggesting that the virus was transmitted from animals being sold as exotic food to humans. COVID-19 is mainly spread from person to person through airborne droplets that are coughed or sneezed out by an infected person. People may also get a COVID-19 infection by touching something that has the virus on it and then touching their own mouth, nose, or eyes. The newly identified coronavirus that causes COVID-19 has been called SARS-CoV2 although it is slightly different from the coronavirus that causes SARS.


Most people infected with COVID-19 have mild symptoms or no symptoms at all, but some become severely ill and die. Symptoms can include fever, cough, and shortness of breath.

Symptoms usually appear about 1 to 14 days after people are infected.


  • Tests to identify the virus

Doctors suspect COVID-19 in people who have flu-like symptoms and have traveled to or live in an area where they could have been exposed to the virus or who have had recent close contact with someone who may have had COVID-19.

Tests, such as a polymerase chain reaction (PCR) test, can be done on upper and lower respiratory secretions to identify the virus. In the US, these tests have recently been done only at the Centers for Disease Control and Prevention (CDC), but tests are starting to become available through certain other laboratories. People’s public health departments will be a source of local information on testing.


To help prevent transmission, people are being quarantined (isolated) when they have been exposed to people with the virus or if they test positive for the virus.

The best way to prevent infection is to avoid being exposed to this virus, which can be difficult because some infected people do not know they have the virus. The CDC recommends the following routine actions to help prevent the spread of respiratory viruses (see CDC’s Prevention and Treatment):

  • Washing hands often with soap and water for at least 20 seconds, especially after going to the bathroom, before eating, and after blowing the nose, coughing, or sneezing

  • Using an alcohol-based hand sanitizer with at least 60% alcohol if soap and water are not readily available

  • Always washing hands with soap and water if hands are visibly dirty

  • Avoiding touching eyes, nose, and mouth with unwashed hands

  • Avoiding close contact with people who are sick

  • Staying home when sick

  • Covering cough or sneeze with a tissue, then throwing the tissue in the trash

  • Cleaning and disinfecting frequently touched objects and surfaces using a regular household cleaning spray or wipe


  • Drugs to relieve fever and muscle aches

There is no vaccine, antiviral drug, or specific treatment for COVID-19. Acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen, is given to relieve fever and muscle aches. Some people become so severely ill that they need to be treated with mechanical ventilation to assist their breathing.

More Information

Middle East Respiratory Syndrome (MERS)

Middle East respiratory syndrome is a coronavirus infection that causes severe flu-like symptoms.

The virus that causes Middle East respiratory syndrome (MERS) is a coronavirus similar to the virus that causes severe acute respiratory syndrome (SARS).

The MERS virus was first detected in Jordan and Saudi Arabia in 2012. As of early 2018, there were 2,220 confirmed cases of MERS and 790 deaths. Most occurred in Saudi Arabia, where new cases continue to appear. Cases have also occurred in countries outside the Middle East, including France, Germany, Italy, Tunisia, and the United Kingdom in people who had been traveling or working in the Middle East.

An outbreak of MERS coronavirus occurred in South Korea from May to July 2015 after a South Korean man returned from the Middle East. This outbreak involved more than 180 cases and 36 deaths. Most person-to-person spread occurred in health care settings.

In May 2014, two cases were confirmed in the United States. Both were health care workers who had recently returned from the Persian Gulf. There have been no MERS cases in the United States since May 2014.

In several countries (including Egypt, Oman, Qatar, and Saudi Arabia), dromedary camels are suspected of being the primary source of infection for people, but how the virus spreads from camels to people is unknown.

The infection is more common among men and is more severe in older people and in people with an underlying chronic disorder such as diabetes or a heart or kidney disorder. The infection has been fatal in about one third of infected people.

The MERS virus is spread through close contact with people who have MERS or through airborne droplets that were coughed or sneezed out by an infected person. People are not thought to be contagious until symptoms develop. Most cases of person-to-person spread have occurred in health care workers caring for infected people.

Symptoms usually appear about 5 days (but anywhere from 2 to 14 days) after people are infected. Most people have a fever, chills, muscle aches, and cough. About one third have diarrhea, vomiting, and abdominal pain.


  • Testing of fluids from the respiratory tract

  • Blood tests

Doctors suspect MERS in people who have a lower respiratory tract infection and have traveled to or reside in an area where they could have been exposed to the virus or who have had recent close contact with someone who may have had MERS.

To diagnose MERS, doctors take a sample of fluids from several places in the respiratory tract at different times and test it for the virus. They also do blood tests to detect the virus or antibodies to it. Blood tests are done on all people who have had close contact with someone who may have MERS.


  • Drugs to relieve fever and muscle aches

  • Isolation

There is no specific treatment for MERS. Acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen are given to relieve fever and muscle aches.

Precautions are taken to prevent the spread of the virus. For example, the person is isolated in a room with a ventilation system that limits the spread of microorganisms in the air. People who go into the room must wear a special mask, eye protection, and a gown, cap, and gloves. Doors to the room should be kept closed except when people enter or leave the room, and people should enter and leave as few times as possible.

People traveling to the Middle East should check the World Health Organization (WHO) web site for travel advice (see WHO World-travel advice on MERS-CoV for pilgrimages).

Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory syndrome is a coronavirus infection that causes flu-like symptoms.
  • No cases had been reported worldwide since 2004.

  • Symptoms of SARS resemble those of other more common respiratory viral infections (such as fever, headache, chills, and muscle aches) but are more severe.

  • Doctors suspect SARS only if people may have been exposed to an infected person.

  • If doctors think a person may have SARS, the person is isolated in a room with a ventilation system that limits the spread of microorganisms in the air.

Severe acute respiratory syndrome (SARS) was first detected in China in late 2002. A worldwide outbreak occurred, resulting in more than 8,000 cases worldwide, including Canada and the United States, and more than 800 deaths by mid 2003. No cases had been reported worldwide since 2004, and SARS (the disease, but not the virus) is considered to have been eradicated.

The immediate source was presumed to be civets, cat-like mammals, that were being sold in live animal markets as exotic food. How civets became infected is unclear, though bats are thought to be the reservoir host of the SARS virus in nature.

SARS is caused by a coronavirus. SARS is much more severe than most other coronavirus infections, which usually cause only coldlike symptoms. However, the Middle East respiratory syndrome (MERS) is another severe illness caused by a coronavirus.

SARS is spread from person to person through close contact with an infected person or through airborne droplets that were coughed or sneezed out by an infected person.


Symptoms of SARS resemble those of other more common respiratory viral infections but are more severe. They include fever, headache, chills, and muscle aches, followed by a dry cough and sometimes difficulty breathing.

Most people recovered within 1 to 2 weeks. However, some developed severe difficulty breathing, and about 10% died.


  • A doctor’s evaluation

  • Tests to identify the virus

SARS is suspected only if people who may have been exposed to an infected person have a fever plus a cough or difficulty breathing.

Tests can be done to identify the virus.


  • Isolation

  • If needed, oxygen

  • Sometimes a ventilator to help with breathing

If doctors think a person may have SARS, the person is isolated in a room with a ventilation system that limits the spread of microorganisms in the air. In the first and only outbreak of SARS, such isolation kept the virus from being transmitted and eventually eliminated it.

People with mild symptoms need no specific treatment. Those with moderate difficulty breathing may need to be given oxygen. Those with severe difficulty breathing may need mechanical ventilation to aid breathing.


Merck Manual

#Características clínicas de #pneumonia refratária por #Covid-19

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médico avaliando raio x de paciente com pneumonia por covid-19

Embora mais de 80% dos casos de Covid-19 sejam leves ou moderados, a infecção pode assumir um curso grave. Nesse contexto, medidas de suporte podem não ser suficientes e as taxas de letalidade são altas.

Um estudo chinês recentemente publicado procurou avaliar características clínicas de pacientes diagnosticados com infecção por SARS-CoV-2 e que desenvolveram pneumonia refratária.

Pneumonia refratária a Covid-19

Trata-se de um estudo retrospectivo, em um único centro, que incluiu todos os pacientes com casos confirmados de Covid-19 internados em um hospital de referência em Wuhan no período de 1° de janeiro a 5 de fevereiro.

Os casos de infecção foram confirmados pela detecção de RNA viral em swabs de orofaringe por meio da técnica de PCR. Pacientes internados foram classificados como tendo caso geral de Covid-19 se apresentassem os seguintes critérios: melhora óbvia dos sintomas respiratórios (como tosse, desconforto torácico e dispneia) depois de tratamento, estar afebril por três dias ou mais sem uso de corticoides ou antipiréticos, melhora de alterações radiológicas em TC ou Rx de tórax depois do tratamento e internação hospitalar por 10 dias ou menos. Caso contrário, os participantes foram classificados como tendo Covid-19 refratária.

Na admissão, doença grave foi definida como a presença de pelo menos um: frequência respiratória ≥ 30 irpm, sO2 ≤ 93% em repouso ou P/F ≤ 300. Casos críticos foram definidos como os que apresentavam pelo menos um dos seguintes: insuficiência respiratória e necessidade de ventilação mecânica, choque ou disfunção orgânica com necessidade de internação em CTI.

Dados clínicos, laboratoriais, radiológicos e sociodemográficos foram retirados dos registros em prontuários eletrônicos. Na análise multivariada, os resultados foram ajustados pela gravidade da doença, ventilação mecânica e transferência para CTI.



No total, 155 pacientes foram incluídos no estudo. A média de idade foi de 54 anos e a maioria dos pacientes eram homens (55,5%). Em relação à presença de comorbidades, 45,8% tinham pelo menos uma comorbidade, sendo hipertensão a mais frequente (23,9%), seguida de diabetes (9,7%) e doenças cardiovasculares (9,7%). Os sintomas mais comuns incluíram febre (81,3%), fadiga (73,2%), tosse (62,6%) e mialgia/artralgia (61%). Sintomas gastrointestinais foram raros. À admissão, 55 (35,5%) e 37 pacientes (23,9%) foram categorizados como tendo doença grave ou crítica, respectivamente.

Após internação hospitalar, 70 pacientes (45,2%) obtiveram remissão clínica e radiológica dentro de dez dias. Quando comparados com esses pacientes, os participantes identificados como tendo Covid-19 refratária eram mais velhos (p < 0,001) e mais frequentemente homens (p = 0,011). Da mesma forma, possuíam mais comorbidades (p < 0,001), incluindo diabetes (p = 0,039), doenças cardiovasculares (p = 0,002) e doenças cerebrovasculares (p = 0,039), menor incidência de febre (p = 0,012), maiores temperaturas entre aqueles que fizeram febre (p = 0,005) e maior incidência de dispneia (p = 0,009), anorexia (p = 0,005) e doença grave na admissão (p < 0,001).

À admissão, a maioria dos pacientes apresentava linfopenia e alterações em neutrófilos, plaquetas, transaminases, LDH e marcadores inflamatórios. Alterações radiológicas foram comuns, com 92,3% apresentando pneumonia bilateral e 10,3%, derrame pleural. Pacientes com Covid-19 refratária apresentaram maiores valores de neutrófilos (p = 0,017), TGO (p = 0,004), LDH (p – 0,017) e PCR (p = 0,001), e menores valores de albumina (p = 0,001) e plaquetas (p = 0,049). Além disso, tinham maior incidência de pneumonia bilateral (p = 0,031) e derrame pleural (p = 0,006).

Na análise multivariada, sexo masculino (p = 0,047; OR = 2,206, IC 95% = 1,012 – 4,809) e anorexia na admissão (p = 0,003; OR = 3,921; IC 95% = 1,144 – 13,443) foram encontrados como fatores de risco, enquanto a presença de febre foi fator protetor (p = 0,0039; OR = 0,331; IC 95% = 0,116 – 0,945).


Mensagens práticas

  • Os dados corroboram que indivíduos mais velhos apresentam maior risco de doença grave por SARS-CoV-2. Homens idosos e com comorbidades podem configuram um grupo particular com doença mais grave e mais difícil de tratar;
  • Alterações radiológicas bilaterais foram frequentes. Chama a atenção a presença de casos de derrame pleural, pouco descrita em outras séries de casos publicadas até então;
  • Da mesma forma, destaca-se a presença de febre como fator protetor de doença refratária. Os autores mencionam que esse resultado sugere que pacientes com resposta lenta ou escassa ao vírus estão sob risco de doença refratária;
  • Linfopenia não foi capaz de diferenciar entre os doentes com boa evolução e os que evoluíram com doença refratária. Pacientes refratários apresentaram aumento marcante de LDH e PCR ao longo da evolução.


Isabel Cristina Melo Mendes

Infectologista pelo Hospital Universitário Clementino Fraga Filho (UFRJ) ⦁ Graduação em Medicina na Universidade Federal do Rio de Janeiro

Referências bibliográficas:

  • Mo, P, Xing, Y, Xiao, Y, Deng, L, Zhao, Q, Wang, H, Xiong, Y, Cheng, Z, Gao, S, Liang, K, Luo, M, Chen, T, Song, S, Ma, Z, Chen, X, Zheng, R, Cao, Q, Wang, F, Zhang, Y. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clinical Infectious Diseases, ciaa270, https://doi.org/10.1093/cid/ciaa270

#Coronavírus: qual a relação entre #vitamina D e #infecções respiratórias?

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Identificada em 1920 como uma vitamina, o calciferol hoje é definido como um pró-hormônio. Dieta e exposição solar são as formas naturais de se obter a vitamina D. Essas duas vias trazem a forma inativa do calciferol e necessita ser ativado pelo fígado e se tornar 25-hidroxivitamina D, forma ativa do composto. Nos rins a 25-hidroxivitamina D se torna um hormônio biologicamente ativo, a 1,25 hidroxivitamina D.

Vitamina D e coronavírus

Nos últimos anos, a vitamina D ganhou muito espaço na mídia e é citada como agente capaz de trazer resultados positivos em diversas condições, especialmente relacionadas a imunidade e infecções de vias respiratórias.

No contexto da pandemia do coronavírus, faz-se necessária uma revisão das evidências atuais sobre tal assunto de visando o melhor serviço de orientações e prescrição sobre vitamina D.

A relação entre vitamina D e sistema imune é complexa e suas vias metabólicas ainda não são completamente descritas nem entendidas pelos pesquisadores.

Vamos às evidências!

Em 2017, o British Journal of Medicine publicou uma revisão sistemática e meta-análise de estudos clínicos randomizados sobre esse assunto: suplementação de vitamina D e prevenção de infecções respiratórias agudas.

Metodologia: Foram elegíveis os estudos clínicos randomizados, duplo-cegos, controlados com placebo com vitamina D3 ou D2 por qualquer tempo de duração. Restaram 25 estudos elegíveis com n=10 933 participantes. Pacientes de toda as faixas de idades participaram do estudo, desde o nascimento até os 95 anos.

Resultados: A suplementação com vitamina D se mostrou protetiva contra infecções agudas do trato respiratório. Quando divididas em subgrupos o subgrupo com níveis séricos < 25 nmol/L mostrou se beneficiar das suplementação (P=0,002), com um número necessário ao tratamento (NNT) de 8 (5-21) porém o subgrupo com níveis de vitamina D > 25 nmol/L não mostraram diferença estatisticamente significativa (P=0,15). Quanto menor eram os níveis de vitamina D, abaixo de 25 nmol/L, maior era a proteção da suplementação de vitamina D contra infecções do trato respiratório.


A suplementação diária ou semanal da vitamina D se mostrou eficaz em diversos estudos clínicos. O nível basal e frequência de dosagem se mostraram variáveis estatisticamente significativas no processo, porém a idade não foi uma variável importante. Isso mostra que o mais importante é manter um nível basal de vitamina D acima de 25 nmol/L durante o ano todo (por isso a frequência de dosagens é importante), independente da idade ou da posologia diária ou semanal.

A suplementação em altas doses agudas parece não ser indicada por causas flutuações demasiada grandes nos níveis basais de vitamina D e causarem desregulação de enzimas responsáveis pela síntese e degradação da forma 1,25 hidroxivitamina D, reduzindo assim as concentrações dessa substância nos tecidos extrarrenais.



O estudo mostrou que a suplementação de vitamina D, mantendo os níveis dentro dos valores de referência, se mostrou segura e com raros efeitos adversos (hipercalcemia 0,5% e nefrolitíase 0,2%).

Dessa forma a orientação mais atual e baseada em evidência sobre a relação da vitamina D com infecções do trato respiratório é: existe sim relação. Paciente com níveis de vitamina D abaixo de 25 nmol/L devem receber suplementação na dose necessária para atingir valores acima de 25 nmol/L. Dose diárias ou semanais são seguras e eficazes, porém, altas doses agudas podem não trazem mais benefícios e, por hoje, devem ser desencorajadas.


Victor Miranda

Residência Médica em Medicina do Exercício e do Esporte (IAMSPE) ⦁ Título de Especialista em Medicina do Exercício e do Esporte  (MEE) ⦁ Preceptor da residência médica de MEE ⦁ Diretor da Sociedade Paulista de Medicina Desportiva (SPAMDE) ⦁ Assessor de Comunicação na diretoria da Sociedade Brasileira de MEE ⦁ Conteudista do Whitebook ⦁ Médico da Care Club ⦁ Criador do curso online Diabetes Revertido ⦁ Sócio fundador do Além da Medicina – instagram @alem.da.medicina

Referências bibliográficas:

  • Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. Published 2017 Feb 15. doi:10.1136/bmj.i6583
  • Rosen CJ, Taylor CL. Common misconceptions about vitamin D–implications for clinicians. Nat Rev Endocrinol. 2013;9(7):434–438. doi:10.1038/nrendo.2013.75

#COVID-19 : les recommandations du CNGOF pour la prise en charge de l’IVG

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France – L’épidémie de Covid-19 bouleverse les pratiques médicales, y compris potentiellement celles touchant aux droits sexuels et reproductifs des femmes. Le gouvernement se dit néanmoins mobilisé sur ce sujet. Aussi, a-t-il été rappelé par le Ministère des Solidarités et de la Santé que les interruptions de grossesse sont considérées comme des interventions urgentes.

Comment assurer le droit à l’IVG aujourd’hui ? Quels sont les changements pour les femmes et pour les soignants qui les prennent en charge ? Le Collège national des gynécologues et obstétriciens français (CNGOF) vient de donner des recommandations.

« La situation dans le Grand Est a une semaine d’avance sur le reste du territoire. Nous constatons, pour le moment, que les choses se passent bien pour les IVG et les accouchements » indique le Pr Israël Nisand (CHU de Strasbourg), président du CNGOF, interrogé par Medscape édition française. « La situation de la France pour les IVG est encore très favorable » insiste-t-il.

Ceci dit, la pratique est déjà bouleversée par l’épidémie si bien que le CNGOF a donné ses premières recommandations pour la prise en charge des IVG durant cette période exceptionnelle. Avec deux lignes de conduite : le droit des femmes à l’accès à l’IVG et la protection des soignants.

Limitation des consultations

Le CNGOF préconise une limitation des consultations avec notamment l’annulation des consultations de contraception et des consultations post IVG. Si la patiente rapporte un problème quand le médecin l’appelle pour annuler la consultation post IVG, elle est alors orientée vers les urgences gynécologiques.

En revanche, le Collège conseille le maintien des consultations pour demande d’IVG. Celles-ci peuvent se faire en téléconsultation.

Des IVG chirurgicales sous anesthésie locale

En cas de grossesse non désirée, le CNGOF émet plusieurs préconisations selon les situations :

  • Jusqu’à 7 semaines d’aménorrhées : il faut privilégier les IVG médicamenteuses à domicile, dont le contrôle se fait par le dosage HCG qui sera transmis au centre.
  • Au-delà de 7 semaines d’aménorrhées : la première consultation est réalisée de façon dématérialisée de préférence. Le CNGOF préconise ensuite de grouper les soins dans une unité de temps et de lieu (consultation gynécologique, avec l’anesthésiste, prélèvements biologiques, échographie de datation) et de ne pas accepter d’accompagnants.

« Il faut absolument privilégier les IVG médicamenteuses. En cas d’IVG chirurgicale, elle sera faite sous anesthésie locale. Nous avons un souci d’épargner des intubations aux collègues anesthésistes afin d’éviter les contaminations » explique le Pr Nisand.

Dans un communiqué commun du 23 mars, Olivier Véran, Ministre des Solidarités et la Santé et Marlène Schiappa, Secrétaire d’Etat auprès du Premier ministre, chargée de l’Égalité entre les femmes et les hommes et de la Lutte contre les discriminations, ont rappelé que « les médecins en ville et les sages-femmes sont autorisés à conseiller les femmes et leurs partenaires sur les questions de contraception. Ils rappellent que ces mêmes professionnels conventionnés avec un établissement de santé sont habilités à réaliser des IVG médicamenteuses sans passer par l’hôpital. A noter, depuis l’arrêté du 19 mars 2020, les sages-femmes peuvent, comme les médecins, pratiquer des consultations à distance.

Que faire en cas de dépassement du délai légal ?

Quand la grossesse est découverte à proximité du délai légal, il s’agit d’une urgence et l’IVG doit être réalisée sans tarder. « Une suspicion de Covid-19 chez une patiente ne doit pas augmenter le délai d’intervention, mais il faut veiller à la mise en œuvre de mesures de protection pour les soignants et les autres patientes » rappelle le gynécologue strasbourgeois.

Les femmes qui dépassent le délai de 14 semaines doivent être orientées vers des hôpitaux qui accepteront de réaliser une interruption médicale de grossesse (IMG) pour cause psychosociale, explique Israël Nisand.



#Despite strict controls, some #infants born to #mothers with COVID-19 appear infected

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Despite implementation of strict infection control and prevention procedures in a hospital in Wuhan, China, a minority of neonates born to mothers with COVID-19 tested positive with novel coronavirus 2019 shortly after birth, according to Lingkong Zeng, MD, of the department of neonatology at Wuhan Children’s Hospital, and associates.

Thirty-three neonates born to mothers with COVID-19 were included in the study, published as a research letter in JAMA Pediatrics. Of this group, three neonates (9%) were confirmed to be infected with the novel coronavirus 2019 at 2 and 4 days of life through nasopharyngeal and anal swabs.

Of the three infected neonates, two were born at 40 weeks’ gestation and the third was born at 31 weeks. The two full-term infants had mild symptoms such as lethargy and fever and were negative for the virus at 6 days of life. The preterm infant had somewhat worse symptoms, but the investigators acknowledged that “the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than [the novel coronavirus 2019] infection.” They added that outcomes for all three neonates were favorable, consistent with past research.

“Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of [novel coronavirus 2019] in the neonates’ upper respiratory tracts or anuses were maternal in origin,” Dr. Zeng and associates surmised.

While previous studies have shown no evidence of COVID-19 transmission between mothers and neonates, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for the novel coronavirus 2019, “vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19,” the investigators concluded.

The study authors reported that they had no conflicts of interest.

SOURCE: Zeng L et al. JAMA Pediatrics. 2020 Mar 26. doi: 10.1001/jamapediatrics.2020.0878.

#COVID-19: cinco enigmas inmunológicos que la ciencia busca responder

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BUENOS AIRES, ARG. A medida que avanza la pandemia y se multiplican los casos de COVID-19 en todo el mundo, emergen nuevos interrogantes sobre la naturaleza de la respuesta inmunológica a la infección. “Si experimento un síntoma, imagino la batalla entre mi sistema inmune y el virus, y qué citocinas se liberan”, expresó el Dr. Michael Saag, especialista en enfermedades infecciosas de University of Alabama, Birmingham, Estados Unidos, quien contrajo la enfermedad y aseguró que nunca había vivido algo parecido.

A continuación algunos enigmas que científicos y médicos intentan o empiezan a responder, y que podrían definir análisis epidemiológicos, conductas terapéuticas y enfoques preventivos.

1. ¿Cuándo aparecen los anticuerpos contra el virus?

Los anticuerpos contra SARS-CoV-2 pueden aparecer entre 5 y 7 días después del inicio del cuadro clínico, aunque la respuesta es variable: un estudio chino aún no revisado por pares sobre 173 pacientes mostró que menos de 40% había presentado seroconversión antes del día 7, aunque la proporción creció a 100%, 94,3%, y 79,8% para anticuerpos totales, inmunoglobulina M e inmunoglobulina G, respectivamente, después del día 15.[1]

Otro estudio australiano documentó la cinética de la respuesta inmune robusta en una paciente de 47 años con COVID-19 no severo, y detectó células plasmáticas secretoras de anticuerpos a partir del día 7, con un pico, el día 8.[2] Según el Dr. Fernando Fariñas, director de Instituto de Patología y Enfermedades Infecciosas de Málaga e integrante del comité científico de la Fundación io, en España, “se especula que a más tarde aparezcan estos anticuerpos, el cuadro evolucionará peor”.[3]

2. ¿Cuánto tiempo persisten esos anticuerpos? ¿Son protectores?

Nadie lo sabe. En su cuenta de Twitter, la Dra. Krutika Kuppalli, profesora en la división de enfermedades infecciosas y medicina geográfica del Center for Innovation in Global Health de Stanford University School of Medicine, en Stanford, Estados Unidos, escribió: “Sabemos que los pacientes desarrollan una respuesta de anticuerpos, pero no está claro todavía si son protectores y por cuánto tiempo”.

Dr. William Moss

En diálogo con Medscape en español, el Dr. William Moss, director ejecutivo del International Vaccine Accessde la Johns Hopkings Bloomberg School of Publich Health, en Baltimore, Estados Unidos, señaló: “Todavía necesitamos aprender qué niveles de anticuerpos son protectores contra la reinfección o enfermedad, y por cuánto tiempo esos niveles de anticuerpos persisten. Muchas infecciones virales respiratorias resultan en una inmunidad protectora de largo plazo, y ese podría ser el caso para SARS-CoV-2, pero no lo sabemos con certeza todavía. A medida que aumente la disponibilidad de las pruebas para medir anticuerpos, y muchos laboratorios están trabajando en eso, seremos capaces de responder estas muy importantes preguntas”.

3. ¿Puede haber reinfección?

Esta pregunta se relaciona con la anterior. Aunque se han reportado algunos posibles casos de reinfección, no confirmados, la mayoría de los médicos e investigadores considera que los pacientes quedan inmunizados, al menos en el corto y mediano plazos. Un reciente estudio chino en monos Rhesus, expuestos al SARS-CoV-2 un mes después de la primera infección, y que no presentaron síntomas ni evidencias de replicación viral, sugiere que la infección primaria podría proteger de exposiciones posteriores.[4] De cualquier manera se ignora si esos anticuerpos reflejan la respuesta inmune inicial o una memoria inmunológica más duradera.

No hay evidencia que muestre de manera convincente que la reinfección haya ocurrido (en pacientes humanos), afirmó el día 25 la Dra. Angela Rasmussen, Ph. D., viróloga del Center for Infection and Immunity, de Columbia Mailman School of Public Health, en Nueva York, Estados Unidos, en Twitter #AskReuters.

La situación podría cambiar si el virus mutara de manera sustancial, pero no parece ser el caso. No estamos viendo que se den esas mutaciones y que las personas se vuelvan a enfermar. Pero es un virus nuevo y estamos aprendiendo constantemente, señaló la Dra. Paula Zingoni, especialista en medicina familiar, y magíster en salud pública, directora de Planificación Operativa de la Ciudad de Buenos Aires.

“La inmunidad a algunas infecciones virales puede ser de corto plazo si el virus muta rápido. Pero tenemos alguna evidencia de que SARS-CoV-2 no parece tener una tasa de mutación alta, por lo que una inmunidad protectora de largo plazo es posible”, señaló el Dr. Moss a Medscape en español.

4. ¿Qué determina que algunas personas se enfermen gravemente y otras apenas presenten síntomas?

No existe una respuesta única, y pueden influir factores tales como estado general de salud, predisposición genética, grado de exposición al virus y hasta tipo de asistencia recibida. En un artículo publicado en Cell Death & Differentiation, científicos de China e Italia propusieron que la respuesta inmune a la infección viral ocurre en dos fases:[5] durante la incubación y los estadios no severos, la respuesta adaptativa inmune puede eliminar el virus y evitar la progresión; pero cuando el virus se propaga, puede ocasionar la destrucción masiva de tejidos afectados y las células dañadas inducen una inflamación en los pulmones que está mediada por macrófagos y granulocitos proinflamatorios.

El Dr. Fariñas escribió que algunos pacientes pueden mostrar especial predisposición a desarrollar hiperrespuesta a la infección, induciendo un estado hiperinflamatorio a través de la llamada tormenta de citocinas. “Finalmente, esta respuesta hiperinflamatoria es la responsable del estado clínico grave del enfermo, e incluso puede producir la muerte. Por tanto, afirmó que es muy importante controlar dicha respuesta en este subgrupo de enfermos”.

La desregulación inmunitaria ocasionada por el virus de COVID-19 y el síndrome de activación macrofágica que se desencadena en los casos severos “es un incendio sobre un fuego que baila sobra lava mientras hace malabarismos sobre un volcán”, puntualizó el Dr. Alberto García Salido, pediatra intensivista y escritor español muy activo en redes sociales.

Un importante documento de la Sociedad Argentina de Inmunología asegura que el aumento de citocinas inflamatorias interleucina-1, interleucina-6, interleucina-8 y factor de necrosis tumoral-alfa preceden la tormenta inflamatoria, mientras que la linfopenia de células CD4+ y el aumento del compartimento T de células CD4+ vírgenes y la disminución de células CD4+ efectoras también son un rasgo de mal pronóstico.[6]

5. ¿Puede haber alguna protección cruzada por infecciones previas con otros coronavirus?

A comienzos de marzo, un estudio alemán con muestras de suero de pacientes convalecientes de la infección por el SARS-CoV, coronavirus que causa el síndrome respiratorio agudo severo, sugirió que la respuesta de anticuerpos neutralizantes puede ofrecer alguna protección contra la infección por SARS-CoV-2.

Sin embargo, eso no significa que los pacientes recuperados del brote de síndrome respiratorio agudo severo de 2002-2003 mantengan a la fecha niveles protectores de anticuerpos. Y para la Dra. Rasmussen, de Columbia, todavía no hay evidencia de inmunidad cruzada con otros coronavirus.

Dr. Roberto Debbag

“Los anticuerpos del síndrome respiratorio agudo severo duran hasta 4 años (aunque la media en un estudio de 2007 fue de 2 años);[7] los del síndrome respiratorio del Medio Oriente, 2 años, y los del resfrío común en la infancia por coronavirus, de 3 a 5 años. No descarto que los niños se enfermen menos con el SARS-CoV-2 porque haya algo de protección cruzada, aunque habría que investigarlo, comentó a Medscape en español el Dr. Roberto Debbag, vicepresidente de la Sociedad Latinoamericana de Infectología Pediátrica.

El Dr. Debbag también recomendar la vacunación contra influenza y neumococo en mayores de 65 años, especialmente en el hemisferio sur, no porque protejan contra COVID-19, sino porque evita tener que buscar atención sanitaria en caso de contraer estas enfermedades, así como el efecto confundidor frente a la infección por coronavirus.

#Haloperidol, #risperidona y #quetiapina, contraindicados con las #terapias para la #Covid-19

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Ocho sociedades científicas publican un documento de consenso sobre el manejo de la psicofarmacoterapia en personas mayores con tratamientos experimentales frente a la infección por SARS-CoV-2.

Los tratamientos experimentales para la Covid-19 generan aún más incertidumbre si se usan junto con psicofármacos.
Los tratamientos experimentales para la Covid-19 generan aún más incertidumbre si se usan junto con psicofármacos.

Existe “claramente una necesidad” de prescribir de forma conjunta los fármacos experimentales para la Covid-19 y los psicofármacos en pacientes de edad avanzada con síntomas psicóticos. Dado que la escasa experiencia “promueve un escenario de incertidumbre”, ocho sociedades científicas médicas han elaborado el documento Manejo farmacológico de trastornos psicóticos en personas mayores con tratamiento de la infección por Covid-19: interacciones y recomendaciones terapéuticas.

Las sociedades que firman el documento son las de Medicina Familiar y Comunitaria (Semfyc), Geriatría y Gerontología (SEGG), Medicina Interna (SEMI), Neurología (SEN), Psicogeriatría (SEPG), Medicina Geriátrica (Semeg), Psiquiatría (SEP) y Psicogeriatría (SEPG). Los psicofármacos analizados son antipsicóticos, antidepresivos y estabilizadores del ánimo, ansiolíticos e hipnóticos.

El documento resume las principales interacciones entre los fármacos prescritos para trastornos psicóticos y los medicamentos que se emplean para tratar a los pacientes con la Covid-19, teniendo en cuenta que estos pacientes “necesitan un abordaje farmacológico racional que resuelva o palíe los síntomas de agitación psicomotriz o psicosis entre otros”.

Antes y después del ingreso

Las recomendaciones son aplicables a pacientes tratados con algunas de las medicaciones experimentales que presentasen previamente trastornos psicóticos o los inicien durante la estancia hospitalaria o la enfermedad aguda. Aunque aborda específicamente el uso de psicofármacos en personas mayores, sus indicaciones podrían ser extrapolables a población más joven.

Entre sus principales conclusiones está que no se recomienda el uso de antipsicóticos utilizados habitualmente en personas mayores, como son haloperidol, risperidona y quetiapina en el contexto de los tratamientos experimentales para la Covid-19. El motivo es el “alto riesgo de reacciones adversas mediadas por el incremento del intervalo QT, además de interacciones a nivel de citocromos con potenciales reacciones adversas graves”.

Terapias experimentales

Los medicamentos recomendados por los protocolos de la Covid-19 son lopinavir/ritonavircloroquina/hidroxicloroquina y, en casos seleccionados, interferón, tocilizumab o remdesivir. Tanto lopinavir/ritonavir como hidroxicloroquina/cloroquina pueden prolongar el intervalo QT y ya de por sí interaccionan entre sí aumentando este riesgo, por lo que la adición de otro tercer fármaco con este efecto podría aumentar la toxicidad y propiciar la aparición de arritmias.

Otros psicofámacos con potenciales interacciones graves con los medicamentos de la Covid-19 son ziprasidona, clozapina, carbamacepina, citalopram y escitalopram, midazolam, triazolam y diacepam. Entre los potenciales efectos adversos recogidos en el documento están también la agranulocitosis, la neutropenia grave, la depresión respiratoria y la sedación.

Frecuentes en edad avanzada

Después de la esquizofrenia, la demencia es la segunda enfermedad que más frecuentemente produce síntomas psicóticos. A su vez, la demencia afecta al 18% de las personas de 75 a 79, al 26% de las de 80 a 84 años y al 45% a partir de los 85 años. Los autores del documento de consenso explican que en el caso del delirium, aparece en mayor medida en las personas mayores con vulnerabilidad cerebral y puede producir síntomas psicóticos graves, disruptivos, frecuentes, y de difícil manejo en el entorno del ingreso hospitalario

#Reports suggest possible in #utero transmission of novel #coronavirus 2019

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Reports of three neonates with elevated IgM antibody concentrations whose mothers had COVID-19 in two articles raise questions about whether the infants may have been infected with the virus in utero.

The data, while provocative, “are not conclusive and do not prove in utero transmission” of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), editorialists cautioned.

“The suggestion of in utero transmission rests on IgM detection in these 3 neonates, and IgM is a challenging way to diagnose many congenital infections,” David W. Kimberlin, MD, and Sergio Stagno, MD, of the division of pediatric infectious diseases at University of Alabama at Birmingham, wrote in their editorial. “IgM antibodies are too large to cross the placenta and so detection in a newborn reasonably could be assumed to reflect fetal production following in utero infection. However, most congenital infections are not diagnosed based on IgM detection because IgM assays can be prone to false-positive and false-negative results, along with cross-reactivity and testing challenges.”

None of the three infants had a positive reverse transcriptase–polymerase chain reaction (RT-PCR) test result, “so there is not virologic evidence for congenital infection in these cases to support the serologic suggestion of in utero transmission,” the editorialists noted.

Examining the possibility of vertical transmission

A prior case series of nine pregnant women found no transmission of the virus from mother to child, but the question of in utero transmission is not settled, said Lan Dong, MD, of the department of obstetrics and gynecology at Renmin Hospital of Wuhan University in China and colleagues. In their research letter, the investigators described a newborn with elevated IgM antibodies to novel coronavirus 2019 born to a mother with COVID-19. The infant was delivered by cesarean section February 22, 2020, at Renmin Hospital in a negative-pressure isolation room.

“The mother wore an N95 mask and did not hold the infant,” the researchers said. “The neonate had no symptoms and was immediately quarantined in the neonatal intensive care unit. At 2 hours of age, the SARS-CoV-2 IgG level was 140.32 AU/mL and the IgM level was 45.83 AU/mL.” Although the infant may have been infected at delivery, IgM antibodies usually take days to appear, Dr. Dong and colleagues wrote. “The infant’s repeatedly negative RT-PCR test results on nasopharyngeal swabs are difficult to explain, although these tests are not always positive with infection. … Additional examination of maternal and newborn samples should be done to confirm this preliminary observation.”

A review of infants’ serologic characteristics

Hui Zeng, MD, of the department of laboratory medicine at Zhongnan Hospital of Wuhan University in China and colleagues retrospectively reviewed clinical records and laboratory results for six pregnant women with COVID-19, according to a study in JAMA. The women had mild clinical manifestations and were admitted to Zhongnan Hospital between February 16 and March 6. “All had cesarean deliveries in their third trimester in negative pressure isolation rooms,” the investigators said. “All mothers wore masks, and all medical staff wore protective suits and double masks. The infants were isolated from their mothers immediately after delivery.”

Two of the infants had elevated IgG and IgM concentrations. IgM “is not usually transferred from mother to fetus because of its larger macromolecular structure. … Whether the placentas of women in this study were damaged and abnormal is unknown,” Dr. Zeng and colleagues said. “Alternatively, IgM could have been produced by the infant if the virus crossed the placenta.”

“Although these 2 studies deserve careful evaluation, more definitive evidence is needed” before physicians can “counsel pregnant women that their fetuses are at risk from congenital infection with SARS-CoV-2,” Dr. Kimberlin and Dr. Stagno concluded.

Dr. Dong and associates had no conflicts of interest. Their work was supported by the National Key Research and Development Project and others. Dr. Zeng and colleagues had no relevant financial disclosures. Their study was supported by grants from the National Natural Science Foundation of China and Zhongnan Hospital. Dr. Kimberlin and Dr. Stagno had no conflicts of interest.

SOURCE: Dong L et al. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4621; Zeng H et al. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4861.