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Coronavirus infections may lead to delirium and potentially PTSD

May 19, 2020

Science Daily/University College London

People taken ill by coronavirus infections may experience psychiatric problems while hospitalised and potentially after they recover, suggests an analysis of past research led by the UCL Institute of Mental Health with King's College London collaborators.

The systematic review paper, published in The Lancet Psychiatry, compiled results from short- and long-term studies of people hospitalised by recent coronaviruses, namely SARS (Severe acute respiratory syndrome) in 2002-2004, MERS (Middle East respiratory syndrome) in 2012, as well as COVID-19 this year.

COVID-19 is caused by the SARS-CoV-2 virus, a type of coronavirus. Some coronaviruses only cause mild symptoms of the common cold, but SARS-CoV-2 can cause severe respiratory illness, as did SARS-CoV-1 (the virus implicated in the 2002-2004 SARS epidemic) and MERS-CoV, which caused MERS in 2012.

The analysis found that one in four people hospitalised with COVID-19 may experience delirium during their illness, a known problem among hospital patients, which can increase risk of death or extend time in hospital.

The post-recovery effects of COVID-19 are not yet known, so long-term risks such as post-traumatic stress disorder (PTSD), chronic fatigue, depression, and anxiety are based on SARS and MERS studies, which may or may not apply to COVID-19 as well.

Co-lead author Dr Jonathan Rogers (UCL Psychiatry and South London and Maudsley NHS Foundation Trust) said: "Most people with COVID-19 will not develop any mental health problems, even among those with severe cases requiring hospitalisation, but given the huge numbers of people getting sick, the global impact on mental health could be considerable.

"Our analysis focuses on potential mental health risks of being hospitalised with a coronavirus infection, and how psychiatric conditions could worsen the prognosis or hold people back from returning to their normal lives after recovering."

The authors of the new paper analysed 65 peer-reviewed studies and seven recent pre-prints that are awaiting peer review, which included data from over 3,500 people who have had one of the three related illnesses. The review only included results from people who were hospitalised, and not people with more mild cases. The findings cover both acute symptoms during the illness, and long-term outcomes from two months to 12 years.

Almost one in three people hospitalised with SARS or MERS went on to develop PTSD, at an average follow-up time of almost three years, especially if they had ongoing physical health problems. Rates of depression and anxiety were also high, at roughly 15% one year or longer after the illness, with a further 15% also experiencing some symptoms of depression and anxiety without a clinical diagnosis. More than 15% also experienced chronic fatigue, mood swings, sleep disorder or impaired concentration and memory.

While in hospital, a significant minority of people with coronavirus infections experienced delirium symptoms such as confusion, agitation and altered consciousness. Almost 28% of people hospitalised for SARS and MERS experienced confusion, and early evidence from the ongoing pandemic suggests that delirium could be similarly common in COVID-19 patients. The authors found some preliminary evidence that delirium may have been associated with raised mortality during the MERS outbreak.

Co-lead author Dr Edward Chesney (Institute of Psychiatry, Psychology & Neuroscience, King's College London and South London and Maudsley NHS Foundation Trust) said: "We need more research on how to prevent mental health problems in the long term. One possibility might be to reduce social isolation by allowing patients to communicate with their loved ones by using video links."

The body of research also identified some of the risk factors associated with worse mental health outcomes. Researchers found that worrying a lot about the illness was associated with worse mental health in the long run, and healthcare workers had worse long-term mental health outcomes than other groups, while making a good physical recovery predicted better long-term mental health.

Senior author Professor Anthony David (UCL Institute of Mental Health) said: "To avoid a large-scale mental health crisis, we hope that people who have been hospitalised with COVID-19 will be offered support, and monitored after they recover to ensure they do not develop mental illnesses, and are able to access treatment if needed.

"While most people with COVID-19 will recover without experiencing mental illness, we need to research which factors may contribute to enduring mental health problems, and develop interventions to prevent and treat them."

https://www.sciencedaily.com/releases/2020/05/200518184914.htm

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A possible treatment for COVID-19 and an approach for developing others

March 26, 2020

Science Daily/American Society for Microbiology

SARS-CoV-2, the virus that causes COVID-19 disease is more transmissible, but has a lower mortality rate than its sibling, SARS-CoV, according to a review article published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

In humans, coronaviruses cause mainly respiratory infections. Individuals with SARS-CoV-2 may remain asymptomatic for 2 to 14 days post-infection and some individuals likely transmit the virus without developing disease symptoms.

So far, the most promising compound for treating COVID-19 is the antiviral, remdesivir. It is currently in clinical trials for treating Ebola virus infections.

Remdesivir was recently tested in a non-human primate model of MERS-CoV infection. Prophylactic treatment 24 hours prior to inoculation prevented MERS-CoV from causing clinical disease and inhibited viral replication in lung tissues, preventing formation of lung lesions. Initiation of treatment 12 hours after virus inoculation was similarly effective.

Remdesivir has also shown effectiveness against a wide range of coronaviruses. It has already undergone safety testing in clinical trials for Ebola, thereby reducing the time that would be necessary for conducting clinical trials for SARS-CoV-2.

Nonetheless, much work needs to be done to gain a better understanding of the mechanics of SARS-CoV-2. For example, understanding how SARS-CoV-2 interacts with the host ACE2 receptor -- by which SARS-CoV-2 gains entry into the host (whether human or animal) -- might reveal how this virus overcame the species barrier between animals and humans. This could also lead to design of new antivirals.

Although coronaviruses are common in bats, no direct animal source of the epidemic has been identified to date, according to the report. "It is critical to identify the intermediate species to stop the current spread and to prevent future human SARS-related coronavirus epidemics," the researchers write.

https://www.sciencedaily.com/releases/2020/03/200326124159.htm

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Remdesivir prevents MERS coronavirus disease in monkeys

February 13, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.sciencedaily.com/releases/2020/02/200213160128.htm

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