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New Guidance: American College of Physicians Discusses Antibody Response in COVID-19 Immunity

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Because of the novelty of the coronavirus that causes COVID-19, there is not enough evidence to determine whether antibodies produced after exposure are protective against reinfection. As such, the American College of Physicians (ACP) published rapid, evidence-based living practice points in the Annals of Internal Medicine discussing the role of antibodies in, tests for diagnosing, and tests for estimating the prevalence of COVID-19.

Practice Point 1: Antibody Tests for COVID-19 Diagnosis

The ACP does not recommend using SARS-CoV-2 antibody tests to diagnose COVID-19. This recommendation is based on the limited evidence that suggests not all patients with COVID-19 develop antibodies early in the course of their infection, as the presence and levels of antibodies can vary across patients and be dictated by certain disease characteristics.


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The guideline panel adds that clinicians and patients should be mindful that some SARS-CoV-2 antibody tests may provide false-positive results, which are caused by cross-reactivity with antibodies of other coronaviruses.

Studies also suggest that the sensitivity, specificity, and accuracy of currently available antibody tests widely vary, further complicating their use as reliable diagnostic tools. Variation in the sensitivity and specificity of these tests can also contribute to both false-negative and false-positive results, leading to inaccurate conclusions about infection and possibly inappropriate or insufficient treatment.

Practice Point 2: Antibody Tests for Estimating Community Prevalence

Studies suggest that patients develop immune responses following exposure to the novel coronavirus. The evidence shows immunoglobulin (Ig)A and IgM antibodies are detectable in the majority of patients who are infected with the SARS-CoV-2 virus. Nearly all patients also demonstrate detectable IgG and neutralizing antibodies.

Over time, the prevalence and levels of these antibodies may vary by different patient characteristics, disease symptoms, and disease severity. On average, the levels of each of the antibody types peak between 20 to 31 days following symptom onset or polymerase chain reaction diagnosis. Studies also show that the IgM antibodies may persist for up to 115 days and neutralizing antibodies may persist up to 152 days. Therefore, the ACP notes that antibody tests could be feasible options for estimating community prevalence of COVID-19.

Practice Point 3: The Protective Effect of SARS-CoV-2 Antibodies Against Reinfection

There is a paucity of evidence to suggest that natural immunity is conferred by SARS-CoV-2 antibodies. There is no evidence to suggest SARS-CoV-2 antibodies can predict the presence, level, or durability of any conferred natural immunity, especially as it relates to protection against reinfection.

Given that most patients exhibit detectable antibodies at least 100 days after infection, it may be plausible that natural immunity can occur. However, the panel reiterates that there is no direct evidence to answer the question of whether these antibodies can protect against reinfection.

Some literature indicates that both asymptomatic and symptomatic patients can develop an antibody response indicative of natural immunity following COVID-19, but variables such as disease severity, patient factors, type and amount of antibodies developed, as well as the longevity of those antibodies, play an important role.

The guideline panel cites a small study of hospitalized patients with COVID-19 that reported a single possible case of reinfection during the convalescence stage. This patient did not have IgM or IgG antibodies detected at the 4-week follow-up period.

Limitations of the Practice Points

According to the guideline authors, the practice points presented concern only the antibody-mediated natural immunity response in COVID-19 and do not particularly address the involvement of other natural immune responses, including cell-mediated immunity or vaccine-acquired immunity.

Currently, the only evidence-based recommendation for increasing immunity to the SARS-CoV-2 virus and preventing infection is to receive an authorized COVID-19 vaccine. Additional prevention strategies recommended in the guideline include social distancing, wearing a mask in public, quarantining, and regular hand washing.

“Given limited knowledge about the association between antibody levels and natural immunity,” the guideline authors wrote, “patients with SARS-CoV-2 infection and those with a history of SARS-CoV-2 infection should follow recommended infection prevention and control procedures to slow and reduce the transmission of SARS-CoV-2.”

Reference:

Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; for the Scientific Medical Policy Committee of the American College of Physicians. What is the antibody response and role in conferring natural immunity after SARS-CoV-2 infection? Rapid, living practice points from the American College of Physicians (version 1). Ann Intern Med. Published online March 16, 2021. doi:10.7326/M20-7569

This article originally appeared on Infectious Disease Advisor

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Source: https://www.medicalbag.com/home/medicine/american-college-of-physicians-guidelines-antibody-response-in-sars-cov-2-reinfection/

Covid19

The U.S. Has Hit 600,000 COVID Deaths, More Than Any Other Country

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Memorials hang from the front gate of Greenwood Cemetery in New York City during an event organized by Naming the Lost Memorials to remember and celebrate those who died during the COVID-19 pandemic. Spencer Platt/Getty Images hide caption

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Spencer Platt/Getty Images

More than 15 months since the first confirmed death due to COVID-19 in the U.S., the coronavirus pandemic has claimed more than 600,000 lives across the country.

But that trend has slowed from thousands to hundreds per day in recent weeks, thanks largely to the ready availability of vaccines.

Over the winter, the nation was adding about 100,000 deaths each month. But as more and more people were vaccinated — particularly older Americans — the death rate fell precipitously. There are now about 375 deaths per day on average — down from more than 3,000 per day in January.

Worldwide, the U.S. still is reporting the greatest total deaths, followed by Brazil, India and Mexico. The total global death toll stands at 3.8 million.

The U.S. death toll, according to Johns Hopkins University, stood at 600,012 on Tuesday afternoon.

Even so, the cumulative number of deaths in the country clearly shows the recent positive impact of vaccines: Barely a month passed between 400,000 and a half-million deaths, but it has taken nearly four times as long to reach the 600,000 mark. At the same time, the trend in the number of new infections, which has closely mirrored deaths, reached a peak in January of more than 300,000 in a single day. Now the U.S. is hovering around an average of fewer than 15,000 confirmed infections, according to Johns Hopkins.

The positive trends have led many states to lift their coronavirus restrictions — with some dropping mask mandates altogether for vaccinated individuals and eliminating other social distancing requirements.

At the same time, however, many Americans have shown a reluctance to get vaccinated, with just over half of U.S. adults fully immunized. In parts of the Midwest and South, in particular, vaccine rates per 100,000 people still remain relatively low compared with the Northeast and parts of the West Coast, according to data from the U.S. Centers for Disease Control and Prevention. The divide has been particularly marked between rural and urban areas of the country.

Tuesday’s figures follow a study this week showing that a new vaccine, one made by Novavax, is 100% effective against the original strain of the coronavirus that causes COVID-19, and 93% effective against other variants.

The next step is for the company to seek regulatory approval from the Food and Drug Administration, which has issued emergency authorizations for three other vaccines – ones made by Pfizer, Moderna and Johnson & Johnson.

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Source: https://www.npr.org/sections/coronavirus-live-updates/2021/06/15/1006186695/the-u-s-has-hit-600-000-covid-deaths-more-than-any-other-country

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Covid19

Multispecialty Perspectives on Long COVID-19

Published

on

In the year since the global COVID-19 pandemic was declared in March 2020 by the World Health Organization,1 short-term treatments such as prone positioning of patients2 or the use of neutralizing antibody cocktails3 have been optimized, and strategies for patients who remain symptomatic for months or experience long-term sequelae4,5 are being developed. Although several effective vaccines6-9 have been developed and the end of the pandemic is now within sight, the long and laborious healing process for patients with long COVID and society as a whole is only just beginning.

“Politicians, key opinion leaders, and other stakeholders must realize that long-COVID-19 will have a big impact on society. If millions of people feel that they are unable to get back to work, it will mean a lot for society,” said Dr Daniel Kondziella, clinical research associate professor in the Department of Neurology at Rigshospitalet, Copenhagen University Hospital. “The after-effects [of the pandemic] will go on for many years to come.”

The Evidence


Continue Reading

A detailed follow-up of 150 patients who were treated at the University of Tours Hospital in France showed that 2 months after symptom onset, more than half (68%) of patients presented with 1 or more lingering symptom of COVID-19. The most common symptoms included diarrhea (33.3%), anosmia/ageusia (22.7%), flu-like symptoms (21.5%), a greater than 5% weight loss (17.2%), arthralgia (16.3%), chest pain (13.1%), cutaneous signs (11.5%), palpitations (10.9%), and dyspnea (7.7%).8

A longer-term, larger study of 1733 Chinese patients who were followed up at 6 months after hospital discharge revealed that most (63%) of the patients experienced fatigue and muscle weakness, and many reported difficulty sleeping (23%), below-average 6-minute walking distances (24%), anxiety or depression (23%), and diffusion impairments (22%).9

The Respiratory System

SARS-CoV-2 infection primarily affects the respiratory tract, causing pneumonia in severe cases with a proinflammatory response.10,11 “We categorize pneumonia as typical or atypical, involving different parts of the lungs. COVID-19 is an atypical pneumonia,” explained Dr Ali Gholamrezanezhad, a radiologist and assistant professor of clinical radiology with Keck Medicine of the University of Southern California, in Los Angeles.

Because COVID-19 may manifest as an atypical pneumonia, patients with severe disease can present with peripheral or posterior distribution of bilateral, multilobar ground-glass opacification, septal and/or pleural thickening, bronchiectasis, and subpleural involvement.11

In the long term, patients who present with complex lung manifestations seen on computed tomographic imaging are at increased risk for tissue scarring. “For patients who needed to be admitted into the hospital for COVID-19, the number [of patients with scarring] can be up to 30% to 40%. In patients who are not admitted, this number is much less, possibly less than 10%. It depends on the severity of the disease,” Dr Gholamrezanezhad added. For example, 6 weeks after discharge from University Hospital RWTH Aachen in Germany, 33 patients who did not require ventilation still presented with symptoms of fatigue (45%), cough (33%), and dyspnea (33%), but there was no evidence of widespread scarring.12

The Cardiovascular System

Although primarily a disease of the respiratory tract, extrapulmonary symptoms have been highly penetrant across tissue systems,10 and many of the lingering symptoms appear to involve other organs.8,9

Dr Valentina Püntmann, consultant physician, cardiologist, clinical pharmacologist, and assistant professor in the Department of Cardiology at the University Hospital Frankfurt, and colleagues recruited 100 patients who had recently recovered from COVID-19. Most patients had acute illness, with only 33% requiring hospitalization. Using cardiovascular magnetic resonance imaging a median of 71 days after their COVID-19 diagnosis, most patients presented with persistent cardiac involvement.13

“We actually thought we were not going to find anything because we were only permitted to scan patients later in their recovery,” said Dr Püntmann. “We also didn’t think at the time about COVID-19 as a cardiac condition. And yet, we were surprised to see myocardial inflammation, scarring, and also pericarditis persisting a few months after the original infection,” she continued.

In total, 78% of the patients had abnormal cardiovascular magnetic resonance scans, most commonly elevated myocardial native T1 (73%) and T2 (60%), myocardial late gadolinium (32%), and pericardial (22%) enhancement.13 These results are particularly intriguing, as they were sourced primarily from individuals who recovered at home, indicating that patients who experience even mild symptoms can have persistent myocardial inflammation and scarring for months.

“We are following up with these patients regularly, and for many patients, things do get better. They may not get better very quickly, which is perhaps something that is long-COVID specific,” stated Dr Püntmann. “But there is also a number of patients who don’t get better. I think we definitely need to get much better at understanding why some patients don’t improve, as well as work on developing effective treatments that we can administer early.”

The Nervous System

Throughout the pandemic, hospitalized patients have presented with a wide range of neurologic manifestations, thrombotic events, delirium, seizure-like events, encephalopathy, periodic discharges, ischemic lesions, and white matter lesions, among others.14,15 There has been little to no evidence collected during hospitalization to suggest there is widespread infiltration by the SARS-CoV-2 virus across the blood-brain barrier.14,16-17 With little direct evidence, it has been speculated these presentations occur as a result of neuroinflammation.15,18

During a 3-month follow-up of 61 patients admitted to Rigshospitalet, Copenhagen University Hospital in Denmark, nearly half (45.9%) of the patients had persistent central and peripheral nervous system complications.14

“Many patients actually still have affected cognitive ability. The average MOCA [Montreal Cognitive Assessment] score was 22 out of 30. Particularly, patients [who] were discharged from the intensive care unit had 19.5 out of 30, so they’re affected cognitively,” described Dr Michael E. Benros, professor of immuno-psychiatry in the Department of Immunology and Microbiology at the University of Copenhagen.

Dr Kondziella added, “There are 3 main ways by which COVID-19 might affect the nervous system. First, the virus itself has some sort of neurotropism. That means the virus crosses the blood-brain barrier and enters the brain, where it damages the tissue directly. The other option is that there is an autoimmune response by which cross-reaction toward the virus particles induces a neuroinflammatory pathway in the brain. We did find that in our study to a relatively lesser extent, compared to the third category, which is peripheral nervous system damage not directly caused by the virus or by autoimmune responses, but more because of treatment-related disorders.”

Because many of these nervous system manifestations were attributed to treatment-related complications (n=34 vs unresolved [n=4] vs para/postinfectious [n=3]),14 many of the younger, fitter patients likely will improve over time with rehabilitation after several months, predicted Dr Benros. However, patients who experience stroke or other thrombotic events may experience life-long COVID-19 complications.

Psychiatry

The neurologic presentations observed among patients with COVID-19 may have psychiatric consequences. “Symptoms from long-term COVID-19 are commonly fatigue, headache, insomnia, and brain fog,” stated Dr Samoon Ahmad, professor in the Department of Psychiatry at New York University Grossman School of Medicine and Unit Chief of Inpatient Psychiatry at Bellevue Hospital Center. “However, we don’t know whether these symptoms are neurologic or caused by depression.”

Dr Ahmad explained that approximately 30% of patients who recovered from COVID-19 went on to develop post-traumatic stress disorder (PTSD).19,20 Symptoms of PTSD also have been reported in multiple studies of highly exposed individuals working in the healthcare sector.21

The observation of PTSD among healthcare workers is important because it brings to the forefront the fact that by no means do you need to be infected with the virus to be experiencing psychiatric consequences from SARS-CoV-2.

Dr Ahmad expounded, “Using data from 2019, on average we see that around 8% of people have anxiety disorders, and 6% [have] depressive disorders. If you look at the most recent data in a similar population, it is mind-boggling because rates of anxiety and depression have fluctuated between 34% and 42%. It’s just remarkable that during the pandemic, about 4 in 10 adults have reported symptoms of anxiety or depressive disorders.”

Dr Ahmad commented that the extent of the psychiatric consequences from the pandemic are likely far from being realized. Future research is needed to focus on the long-term psychiatric effects among patients who have recovered from severe illness, healthcare workers who were exposed to traumatic situations, the general public who experienced increased loneliness or the loss of loved ones, and children who were isolated because of the suspension of schools.

Future Perspectives

The need for ongoing collection of highly robust data and for the streamlining of definitions, data collection strategies, and patient stratification such that more consistent data become available is apparent. A more collaborative approach to conducting SARS-CoV-2 research would not only improve understanding but allow for more precise communication with the general public, which is imperative for successful vaccination campaigns and COVID-19 rule compliance.

In the meantime, Dr Püntmann implores fellow clinicians not to ignore the exercise intolerance that persists for weeks or months after infection among some COVID-19 patients. They may offer advice to patients to slow down for 3 to 6 months and not try to push themselves back to their former fitness too early. “By [not] doing that, they can make the symptoms a lot worse and slow down their recovery. This may feel very counterintuitive, especially to the young and fit patients because they are used to getting fit as soon as possible after a flu or a cold. Recovery after COVID-19 is a different, much more protracted process.”

The other largely protracted process will be to overcome the long-term stress associated with the pandemic. “In the short term it is easy to put mental health concerns on the back burner. This sort of constant stress will eventually have an impact on mental health in general,” cautioned Dr Ahmad. “At a certain point, people just reach their breaking point.” He stated that there is a great need for large-scale improved access to basic mental health support, such that everyone can be armed with basic tools to reduce stress and develop healthy routines.

References

1. World Health Organization. Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). Published February 16-24, 2020. Accessed June 1, 2021. http://who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

2. Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46(12):2385-2396. doi:10.1007/s00134-020-06306-w

3. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002

4. Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021;21(5):637-646. doi:10.1016/S1473-3099(20)30942-7

5. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

6. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389

7. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. 2021;NEJMoa2034201. N Engl J Med. doi:10.1056/NEJMoa2034201

8. Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021;27(2):258-263. doi:10.1016/j.cmi.2020.09.052

9. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8

10. Behzad S, Aghaghazvini L, Radmard AR, Gholamrezanezhad A. Extrapulmonary manifestations of COVID-19: radiologic and clinical overview. Clin Imaging. 2020;66:35-41. doi:10.1016/j.clinimag.2020.05.013

11. Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A. Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 Patients. AJR Am J Roentgenol. 2020;215(1):87-93. doi:10.2214/AJR.20.23034

12. Daher A, Balfanz P, Cornelissen C, et al. Follow up of patients with severe coronavirus disease 2019 (COVID-19): pulmonary and extrapulmonary disease sequelae. Respir Med. 2020;174:106197. doi:10.1016/j.rmed.2020.106197

13. Puüntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-1273. doi:10.1001/jamacardio.2020.3557

14. Nersesjan V, Amiri M, Lebech A-M, et al. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up. J Neurol. Published online January 13, 202. doi:10.1007/s00415-020-10380-x

15. Lambrecq V, Hanin A, Munoz-Musat E, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw Open. 2021;4(3):e211489. doi:10.1001/jamanetworkopen.2021.1489

16. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062

17. Domingues RB, Mendes-Correa MC, de Moura Leite FBV, et al. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol. 2020;267(11):3154-3156. doi:10.1007/s00415-020-09996-w

18. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. Published online March 26, 2021. doi:10.1001/jamapsychiatry.2021.0500

19. Forte G, Favieri F, Tambelli R, Casagrande M. COVID-19 pandemic in the Italian population: validation of a post-traumatic stress disorder questionnaire and prevalence of PTSD symptomatology. Int J Environ Res Public Health. 2020;17(11):4151. doi:10.3390/ijerph17114151

20. Janiri D, Carfì A, Kotzalidis GD, et al. Posttraumatic stress disorder in patients after severe COVID-19 infection. JAMA Psychiatry. 2021;78(5):567-569. doi:10.1001/jamapsychiatry.2021.0109

21. Tucker P, Czapla CS. Post-COVID stress disorder: another emerging consequence of the global pandemic. Psychiatric Times. 2021;38(1).

This article originally appeared on Infectious Disease Advisor

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Source: https://www.medicalbag.com/home/news/multispecialty-perspectives-on-long-covid-19/

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Covid19

Multispecialty Perspectives on Long COVID-19

Published

on

In the year since the global COVID-19 pandemic was declared in March 2020 by the World Health Organization,1 short-term treatments such as prone positioning of patients2 or the use of neutralizing antibody cocktails3 have been optimized, and strategies for patients who remain symptomatic for months or experience long-term sequelae4,5 are being developed. Although several effective vaccines6-9 have been developed and the end of the pandemic is now within sight, the long and laborious healing process for patients with long COVID and society as a whole is only just beginning.

“Politicians, key opinion leaders, and other stakeholders must realize that long-COVID-19 will have a big impact on society. If millions of people feel that they are unable to get back to work, it will mean a lot for society,” said Dr Daniel Kondziella, clinical research associate professor in the Department of Neurology at Rigshospitalet, Copenhagen University Hospital. “The after-effects [of the pandemic] will go on for many years to come.”

The Evidence


Continue Reading

A detailed follow-up of 150 patients who were treated at the University of Tours Hospital in France showed that 2 months after symptom onset, more than half (68%) of patients presented with 1 or more lingering symptom of COVID-19. The most common symptoms included diarrhea (33.3%), anosmia/ageusia (22.7%), flu-like symptoms (21.5%), a greater than 5% weight loss (17.2%), arthralgia (16.3%), chest pain (13.1%), cutaneous signs (11.5%), palpitations (10.9%), and dyspnea (7.7%).8

A longer-term, larger study of 1733 Chinese patients who were followed up at 6 months after hospital discharge revealed that most (63%) of the patients experienced fatigue and muscle weakness, and many reported difficulty sleeping (23%), below-average 6-minute walking distances (24%), anxiety or depression (23%), and diffusion impairments (22%).9

The Respiratory System

SARS-CoV-2 infection primarily affects the respiratory tract, causing pneumonia in severe cases with a proinflammatory response.10,11 “We categorize pneumonia as typical or atypical, involving different parts of the lungs. COVID-19 is an atypical pneumonia,” explained Dr Ali Gholamrezanezhad, a radiologist and assistant professor of clinical radiology with Keck Medicine of the University of Southern California, in Los Angeles.

Because COVID-19 may manifest as an atypical pneumonia, patients with severe disease can present with peripheral or posterior distribution of bilateral, multilobar ground-glass opacification, septal and/or pleural thickening, bronchiectasis, and subpleural involvement.11

In the long term, patients who present with complex lung manifestations seen on computed tomographic imaging are at increased risk for tissue scarring. “For patients who needed to be admitted into the hospital for COVID-19, the number [of patients with scarring] can be up to 30% to 40%. In patients who are not admitted, this number is much less, possibly less than 10%. It depends on the severity of the disease,” Dr Gholamrezanezhad added. For example, 6 weeks after discharge from University Hospital RWTH Aachen in Germany, 33 patients who did not require ventilation still presented with symptoms of fatigue (45%), cough (33%), and dyspnea (33%), but there was no evidence of widespread scarring.12

The Cardiovascular System

Although primarily a disease of the respiratory tract, extrapulmonary symptoms have been highly penetrant across tissue systems,10 and many of the lingering symptoms appear to involve other organs.8,9

Dr Valentina Püntmann, consultant physician, cardiologist, clinical pharmacologist, and assistant professor in the Department of Cardiology at the University Hospital Frankfurt, and colleagues recruited 100 patients who had recently recovered from COVID-19. Most patients had acute illness, with only 33% requiring hospitalization. Using cardiovascular magnetic resonance imaging a median of 71 days after their COVID-19 diagnosis, most patients presented with persistent cardiac involvement.13

“We actually thought we were not going to find anything because we were only permitted to scan patients later in their recovery,” said Dr Püntmann. “We also didn’t think at the time about COVID-19 as a cardiac condition. And yet, we were surprised to see myocardial inflammation, scarring, and also pericarditis persisting a few months after the original infection,” she continued.

In total, 78% of the patients had abnormal cardiovascular magnetic resonance scans, most commonly elevated myocardial native T1 (73%) and T2 (60%), myocardial late gadolinium (32%), and pericardial (22%) enhancement.13 These results are particularly intriguing, as they were sourced primarily from individuals who recovered at home, indicating that patients who experience even mild symptoms can have persistent myocardial inflammation and scarring for months.

“We are following up with these patients regularly, and for many patients, things do get better. They may not get better very quickly, which is perhaps something that is long-COVID specific,” stated Dr Püntmann. “But there is also a number of patients who don’t get better. I think we definitely need to get much better at understanding why some patients don’t improve, as well as work on developing effective treatments that we can administer early.”

The Nervous System

Throughout the pandemic, hospitalized patients have presented with a wide range of neurologic manifestations, thrombotic events, delirium, seizure-like events, encephalopathy, periodic discharges, ischemic lesions, and white matter lesions, among others.14,15 There has been little to no evidence collected during hospitalization to suggest there is widespread infiltration by the SARS-CoV-2 virus across the blood-brain barrier.14,16-17 With little direct evidence, it has been speculated these presentations occur as a result of neuroinflammation.15,18

During a 3-month follow-up of 61 patients admitted to Rigshospitalet, Copenhagen University Hospital in Denmark, nearly half (45.9%) of the patients had persistent central and peripheral nervous system complications.14

“Many patients actually still have affected cognitive ability. The average MOCA [Montreal Cognitive Assessment] score was 22 out of 30. Particularly, patients [who] were discharged from the intensive care unit had 19.5 out of 30, so they’re affected cognitively,” described Dr Michael E. Benros, professor of immuno-psychiatry in the Department of Immunology and Microbiology at the University of Copenhagen.

Dr Kondziella added, “There are 3 main ways by which COVID-19 might affect the nervous system. First, the virus itself has some sort of neurotropism. That means the virus crosses the blood-brain barrier and enters the brain, where it damages the tissue directly. The other option is that there is an autoimmune response by which cross-reaction toward the virus particles induces a neuroinflammatory pathway in the brain. We did find that in our study to a relatively lesser extent, compared to the third category, which is peripheral nervous system damage not directly caused by the virus or by autoimmune responses, but more because of treatment-related disorders.”

Because many of these nervous system manifestations were attributed to treatment-related complications (n=34 vs unresolved [n=4] vs para/postinfectious [n=3]),14 many of the younger, fitter patients likely will improve over time with rehabilitation after several months, predicted Dr Benros. However, patients who experience stroke or other thrombotic events may experience life-long COVID-19 complications.

Psychiatry

The neurologic presentations observed among patients with COVID-19 may have psychiatric consequences. “Symptoms from long-term COVID-19 are commonly fatigue, headache, insomnia, and brain fog,” stated Dr Samoon Ahmad, professor in the Department of Psychiatry at New York University Grossman School of Medicine and Unit Chief of Inpatient Psychiatry at Bellevue Hospital Center. “However, we don’t know whether these symptoms are neurologic or caused by depression.”

Dr Ahmad explained that approximately 30% of patients who recovered from COVID-19 went on to develop post-traumatic stress disorder (PTSD).19,20 Symptoms of PTSD also have been reported in multiple studies of highly exposed individuals working in the healthcare sector.21

The observation of PTSD among healthcare workers is important because it brings to the forefront the fact that by no means do you need to be infected with the virus to be experiencing psychiatric consequences from SARS-CoV-2.

Dr Ahmad expounded, “Using data from 2019, on average we see that around 8% of people have anxiety disorders, and 6% [have] depressive disorders. If you look at the most recent data in a similar population, it is mind-boggling because rates of anxiety and depression have fluctuated between 34% and 42%. It’s just remarkable that during the pandemic, about 4 in 10 adults have reported symptoms of anxiety or depressive disorders.”

Dr Ahmad commented that the extent of the psychiatric consequences from the pandemic are likely far from being realized. Future research is needed to focus on the long-term psychiatric effects among patients who have recovered from severe illness, healthcare workers who were exposed to traumatic situations, the general public who experienced increased loneliness or the loss of loved ones, and children who were isolated because of the suspension of schools.

Future Perspectives

The need for ongoing collection of highly robust data and for the streamlining of definitions, data collection strategies, and patient stratification such that more consistent data become available is apparent. A more collaborative approach to conducting SARS-CoV-2 research would not only improve understanding but allow for more precise communication with the general public, which is imperative for successful vaccination campaigns and COVID-19 rule compliance.

In the meantime, Dr Püntmann implores fellow clinicians not to ignore the exercise intolerance that persists for weeks or months after infection among some COVID-19 patients. They may offer advice to patients to slow down for 3 to 6 months and not try to push themselves back to their former fitness too early. “By [not] doing that, they can make the symptoms a lot worse and slow down their recovery. This may feel very counterintuitive, especially to the young and fit patients because they are used to getting fit as soon as possible after a flu or a cold. Recovery after COVID-19 is a different, much more protracted process.”

The other largely protracted process will be to overcome the long-term stress associated with the pandemic. “In the short term it is easy to put mental health concerns on the back burner. This sort of constant stress will eventually have an impact on mental health in general,” cautioned Dr Ahmad. “At a certain point, people just reach their breaking point.” He stated that there is a great need for large-scale improved access to basic mental health support, such that everyone can be armed with basic tools to reduce stress and develop healthy routines.

References

1. World Health Organization. Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). Published February 16-24, 2020. Accessed June 1, 2021. http://who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

2. Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46(12):2385-2396. doi:10.1007/s00134-020-06306-w

3. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002

4. Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021;21(5):637-646. doi:10.1016/S1473-3099(20)30942-7

5. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

6. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389

7. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. 2021;NEJMoa2034201. N Engl J Med. doi:10.1056/NEJMoa2034201

8. Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021;27(2):258-263. doi:10.1016/j.cmi.2020.09.052

9. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8

10. Behzad S, Aghaghazvini L, Radmard AR, Gholamrezanezhad A. Extrapulmonary manifestations of COVID-19: radiologic and clinical overview. Clin Imaging. 2020;66:35-41. doi:10.1016/j.clinimag.2020.05.013

11. Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A. Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 Patients. AJR Am J Roentgenol. 2020;215(1):87-93. doi:10.2214/AJR.20.23034

12. Daher A, Balfanz P, Cornelissen C, et al. Follow up of patients with severe coronavirus disease 2019 (COVID-19): pulmonary and extrapulmonary disease sequelae. Respir Med. 2020;174:106197. doi:10.1016/j.rmed.2020.106197

13. Puüntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-1273. doi:10.1001/jamacardio.2020.3557

14. Nersesjan V, Amiri M, Lebech A-M, et al. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up. J Neurol. Published online January 13, 202. doi:10.1007/s00415-020-10380-x

15. Lambrecq V, Hanin A, Munoz-Musat E, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw Open. 2021;4(3):e211489. doi:10.1001/jamanetworkopen.2021.1489

16. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062

17. Domingues RB, Mendes-Correa MC, de Moura Leite FBV, et al. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol. 2020;267(11):3154-3156. doi:10.1007/s00415-020-09996-w

18. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. Published online March 26, 2021. doi:10.1001/jamapsychiatry.2021.0500

19. Forte G, Favieri F, Tambelli R, Casagrande M. COVID-19 pandemic in the Italian population: validation of a post-traumatic stress disorder questionnaire and prevalence of PTSD symptomatology. Int J Environ Res Public Health. 2020;17(11):4151. doi:10.3390/ijerph17114151

20. Janiri D, Carfì A, Kotzalidis GD, et al. Posttraumatic stress disorder in patients after severe COVID-19 infection. JAMA Psychiatry. 2021;78(5):567-569. doi:10.1001/jamapsychiatry.2021.0109

21. Tucker P, Czapla CS. Post-COVID stress disorder: another emerging consequence of the global pandemic. Psychiatric Times. 2021;38(1).

This article originally appeared on Infectious Disease Advisor

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Covid19

Multispecialty Perspectives on Long COVID-19

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In the year since the global COVID-19 pandemic was declared in March 2020 by the World Health Organization,1 short-term treatments such as prone positioning of patients2 or the use of neutralizing antibody cocktails3 have been optimized, and strategies for patients who remain symptomatic for months or experience long-term sequelae4,5 are being developed. Although several effective vaccines6-9 have been developed and the end of the pandemic is now within sight, the long and laborious healing process for patients with long COVID and society as a whole is only just beginning.

“Politicians, key opinion leaders, and other stakeholders must realize that long-COVID-19 will have a big impact on society. If millions of people feel that they are unable to get back to work, it will mean a lot for society,” said Dr Daniel Kondziella, clinical research associate professor in the Department of Neurology at Rigshospitalet, Copenhagen University Hospital. “The after-effects [of the pandemic] will go on for many years to come.”

The Evidence


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A detailed follow-up of 150 patients who were treated at the University of Tours Hospital in France showed that 2 months after symptom onset, more than half (68%) of patients presented with 1 or more lingering symptom of COVID-19. The most common symptoms included diarrhea (33.3%), anosmia/ageusia (22.7%), flu-like symptoms (21.5%), a greater than 5% weight loss (17.2%), arthralgia (16.3%), chest pain (13.1%), cutaneous signs (11.5%), palpitations (10.9%), and dyspnea (7.7%).8

A longer-term, larger study of 1733 Chinese patients who were followed up at 6 months after hospital discharge revealed that most (63%) of the patients experienced fatigue and muscle weakness, and many reported difficulty sleeping (23%), below-average 6-minute walking distances (24%), anxiety or depression (23%), and diffusion impairments (22%).9

The Respiratory System

SARS-CoV-2 infection primarily affects the respiratory tract, causing pneumonia in severe cases with a proinflammatory response.10,11 “We categorize pneumonia as typical or atypical, involving different parts of the lungs. COVID-19 is an atypical pneumonia,” explained Dr Ali Gholamrezanezhad, a radiologist and assistant professor of clinical radiology with Keck Medicine of the University of Southern California, in Los Angeles.

Because COVID-19 may manifest as an atypical pneumonia, patients with severe disease can present with peripheral or posterior distribution of bilateral, multilobar ground-glass opacification, septal and/or pleural thickening, bronchiectasis, and subpleural involvement.11

In the long term, patients who present with complex lung manifestations seen on computed tomographic imaging are at increased risk for tissue scarring. “For patients who needed to be admitted into the hospital for COVID-19, the number [of patients with scarring] can be up to 30% to 40%. In patients who are not admitted, this number is much less, possibly less than 10%. It depends on the severity of the disease,” Dr Gholamrezanezhad added. For example, 6 weeks after discharge from University Hospital RWTH Aachen in Germany, 33 patients who did not require ventilation still presented with symptoms of fatigue (45%), cough (33%), and dyspnea (33%), but there was no evidence of widespread scarring.12

The Cardiovascular System

Although primarily a disease of the respiratory tract, extrapulmonary symptoms have been highly penetrant across tissue systems,10 and many of the lingering symptoms appear to involve other organs.8,9

Dr Valentina Püntmann, consultant physician, cardiologist, clinical pharmacologist, and assistant professor in the Department of Cardiology at the University Hospital Frankfurt, and colleagues recruited 100 patients who had recently recovered from COVID-19. Most patients had acute illness, with only 33% requiring hospitalization. Using cardiovascular magnetic resonance imaging a median of 71 days after their COVID-19 diagnosis, most patients presented with persistent cardiac involvement.13

“We actually thought we were not going to find anything because we were only permitted to scan patients later in their recovery,” said Dr Püntmann. “We also didn’t think at the time about COVID-19 as a cardiac condition. And yet, we were surprised to see myocardial inflammation, scarring, and also pericarditis persisting a few months after the original infection,” she continued.

In total, 78% of the patients had abnormal cardiovascular magnetic resonance scans, most commonly elevated myocardial native T1 (73%) and T2 (60%), myocardial late gadolinium (32%), and pericardial (22%) enhancement.13 These results are particularly intriguing, as they were sourced primarily from individuals who recovered at home, indicating that patients who experience even mild symptoms can have persistent myocardial inflammation and scarring for months.

“We are following up with these patients regularly, and for many patients, things do get better. They may not get better very quickly, which is perhaps something that is long-COVID specific,” stated Dr Püntmann. “But there is also a number of patients who don’t get better. I think we definitely need to get much better at understanding why some patients don’t improve, as well as work on developing effective treatments that we can administer early.”

The Nervous System

Throughout the pandemic, hospitalized patients have presented with a wide range of neurologic manifestations, thrombotic events, delirium, seizure-like events, encephalopathy, periodic discharges, ischemic lesions, and white matter lesions, among others.14,15 There has been little to no evidence collected during hospitalization to suggest there is widespread infiltration by the SARS-CoV-2 virus across the blood-brain barrier.14,16-17 With little direct evidence, it has been speculated these presentations occur as a result of neuroinflammation.15,18

During a 3-month follow-up of 61 patients admitted to Rigshospitalet, Copenhagen University Hospital in Denmark, nearly half (45.9%) of the patients had persistent central and peripheral nervous system complications.14

“Many patients actually still have affected cognitive ability. The average MOCA [Montreal Cognitive Assessment] score was 22 out of 30. Particularly, patients [who] were discharged from the intensive care unit had 19.5 out of 30, so they’re affected cognitively,” described Dr Michael E. Benros, professor of immuno-psychiatry in the Department of Immunology and Microbiology at the University of Copenhagen.

Dr Kondziella added, “There are 3 main ways by which COVID-19 might affect the nervous system. First, the virus itself has some sort of neurotropism. That means the virus crosses the blood-brain barrier and enters the brain, where it damages the tissue directly. The other option is that there is an autoimmune response by which cross-reaction toward the virus particles induces a neuroinflammatory pathway in the brain. We did find that in our study to a relatively lesser extent, compared to the third category, which is peripheral nervous system damage not directly caused by the virus or by autoimmune responses, but more because of treatment-related disorders.”

Because many of these nervous system manifestations were attributed to treatment-related complications (n=34 vs unresolved [n=4] vs para/postinfectious [n=3]),14 many of the younger, fitter patients likely will improve over time with rehabilitation after several months, predicted Dr Benros. However, patients who experience stroke or other thrombotic events may experience life-long COVID-19 complications.

Psychiatry

The neurologic presentations observed among patients with COVID-19 may have psychiatric consequences. “Symptoms from long-term COVID-19 are commonly fatigue, headache, insomnia, and brain fog,” stated Dr Samoon Ahmad, professor in the Department of Psychiatry at New York University Grossman School of Medicine and Unit Chief of Inpatient Psychiatry at Bellevue Hospital Center. “However, we don’t know whether these symptoms are neurologic or caused by depression.”

Dr Ahmad explained that approximately 30% of patients who recovered from COVID-19 went on to develop post-traumatic stress disorder (PTSD).19,20 Symptoms of PTSD also have been reported in multiple studies of highly exposed individuals working in the healthcare sector.21

The observation of PTSD among healthcare workers is important because it brings to the forefront the fact that by no means do you need to be infected with the virus to be experiencing psychiatric consequences from SARS-CoV-2.

Dr Ahmad expounded, “Using data from 2019, on average we see that around 8% of people have anxiety disorders, and 6% [have] depressive disorders. If you look at the most recent data in a similar population, it is mind-boggling because rates of anxiety and depression have fluctuated between 34% and 42%. It’s just remarkable that during the pandemic, about 4 in 10 adults have reported symptoms of anxiety or depressive disorders.”

Dr Ahmad commented that the extent of the psychiatric consequences from the pandemic are likely far from being realized. Future research is needed to focus on the long-term psychiatric effects among patients who have recovered from severe illness, healthcare workers who were exposed to traumatic situations, the general public who experienced increased loneliness or the loss of loved ones, and children who were isolated because of the suspension of schools.

Future Perspectives

The need for ongoing collection of highly robust data and for the streamlining of definitions, data collection strategies, and patient stratification such that more consistent data become available is apparent. A more collaborative approach to conducting SARS-CoV-2 research would not only improve understanding but allow for more precise communication with the general public, which is imperative for successful vaccination campaigns and COVID-19 rule compliance.

In the meantime, Dr Püntmann implores fellow clinicians not to ignore the exercise intolerance that persists for weeks or months after infection among some COVID-19 patients. They may offer advice to patients to slow down for 3 to 6 months and not try to push themselves back to their former fitness too early. “By [not] doing that, they can make the symptoms a lot worse and slow down their recovery. This may feel very counterintuitive, especially to the young and fit patients because they are used to getting fit as soon as possible after a flu or a cold. Recovery after COVID-19 is a different, much more protracted process.”

The other largely protracted process will be to overcome the long-term stress associated with the pandemic. “In the short term it is easy to put mental health concerns on the back burner. This sort of constant stress will eventually have an impact on mental health in general,” cautioned Dr Ahmad. “At a certain point, people just reach their breaking point.” He stated that there is a great need for large-scale improved access to basic mental health support, such that everyone can be armed with basic tools to reduce stress and develop healthy routines.

References

1. World Health Organization. Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). Published February 16-24, 2020. Accessed June 1, 2021. http://who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

2. Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46(12):2385-2396. doi:10.1007/s00134-020-06306-w

3. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002

4. Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021;21(5):637-646. doi:10.1016/S1473-3099(20)30942-7

5. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

6. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389

7. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. 2021;NEJMoa2034201. N Engl J Med. doi:10.1056/NEJMoa2034201

8. Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021;27(2):258-263. doi:10.1016/j.cmi.2020.09.052

9. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8

10. Behzad S, Aghaghazvini L, Radmard AR, Gholamrezanezhad A. Extrapulmonary manifestations of COVID-19: radiologic and clinical overview. Clin Imaging. 2020;66:35-41. doi:10.1016/j.clinimag.2020.05.013

11. Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A. Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 Patients. AJR Am J Roentgenol. 2020;215(1):87-93. doi:10.2214/AJR.20.23034

12. Daher A, Balfanz P, Cornelissen C, et al. Follow up of patients with severe coronavirus disease 2019 (COVID-19): pulmonary and extrapulmonary disease sequelae. Respir Med. 2020;174:106197. doi:10.1016/j.rmed.2020.106197

13. Puüntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-1273. doi:10.1001/jamacardio.2020.3557

14. Nersesjan V, Amiri M, Lebech A-M, et al. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up. J Neurol. Published online January 13, 202. doi:10.1007/s00415-020-10380-x

15. Lambrecq V, Hanin A, Munoz-Musat E, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw Open. 2021;4(3):e211489. doi:10.1001/jamanetworkopen.2021.1489

16. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062

17. Domingues RB, Mendes-Correa MC, de Moura Leite FBV, et al. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol. 2020;267(11):3154-3156. doi:10.1007/s00415-020-09996-w

18. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. Published online March 26, 2021. doi:10.1001/jamapsychiatry.2021.0500

19. Forte G, Favieri F, Tambelli R, Casagrande M. COVID-19 pandemic in the Italian population: validation of a post-traumatic stress disorder questionnaire and prevalence of PTSD symptomatology. Int J Environ Res Public Health. 2020;17(11):4151. doi:10.3390/ijerph17114151

20. Janiri D, Carfì A, Kotzalidis GD, et al. Posttraumatic stress disorder in patients after severe COVID-19 infection. JAMA Psychiatry. 2021;78(5):567-569. doi:10.1001/jamapsychiatry.2021.0109

21. Tucker P, Czapla CS. Post-COVID stress disorder: another emerging consequence of the global pandemic. Psychiatric Times. 2021;38(1).

This article originally appeared on Infectious Disease Advisor

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