There are now sufficient numbers of individuals who have had the coronavirus during the past 15 months who are presenting to their physicians with lingering symptoms of the disease. They are now known as long-haulers. People who have sometimes multiple complaints that suggest to researchers that they are a different group of patients. They tend to be younger, they generally have more complex medical histories including a variety to pulmonary conditions, and they are not the case you might expect to be most debilitated. This report is derived from the literature recent review and live zoom presentation on the Cognitive Impact on Long-haul survivors of the coronavirus held on May 20, 2021. It is available on the Whittier Health website. I want to thank Lauren Guenon, MS, SLP, CBIS for her help in this program and the data mining we are continuing.
It was first reported that overwhelming viral spread was thought to be primarily respiratory. The virus multiplies inside the body and is likely to cause mild symptoms that may be confused with a common cold or flu. This changes in many as the viral load evokes a cytokine autoimmune response in the body. As the virus takes, hold during the worsening pulmonary phase primarily respiratory symptoms such as persistent cough, shortness of breath, and low oxygen levels are observed. Too many survivors say the ignored this phase and just tried to rest at home. Often they were transported to hospital after being overwhelmed by the inflammation in their lungs and other organs. Hyperinflammatory phase, occurs when a hyperactivated immune system may cause injury to the heart, kidneys, and other organs as covid-19 devours healthy cells leading to death of cells in a process called apotosis.
Experience shows most long-haulers were expected to fall into the high risk category. like those with chronic COPD, but there is also a growing percentage of people who were otherwise healthy before they became infected and are not the older, sicker cases first described.
About 33% of COVID-19 patients who were never sick enough to require hospitalization continue to complain months later of symptoms like fatigue, loss of smell or taste and “brain fog,” that can interfere with functional tasks including the return to work.
University of Washington (UW)
It remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they are a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response from their immunocompromised status when infected. 38 males, ages 22-74
The first studies of long haul survivors are being published. They are small studies reporting on the Italian first wave in 2020. The cases are hospitalized, non-intensive COVID units in Milan, Italy. These were not the patients who needed intubation or ventilatory support. Most had ARDS (mild, moderate, severe) Ferrucci, R et al. Subjectively, 31.6% reported overall cognitive decline 4-5 months after discharge when they were screened using a commonly administered cognitive test, then assessed using BRB-NT. Results for this group of moderately infected patients included: 42.1% processing speed deficits; 26.3% delayed verbal recall; 10.5% immediate verbal recall; 18.4% impaired visual long term memory, 15.8% visual short term memory; and 7.9% semantic verbal fluency deficits. Helms et al. reported on 58 patients who were evaluated in the ICU with over a third (33%) exhibiting dysexecutive syndrome, poorly deployed attention, and decreased capacity for organization
In another Italian study, 81% of patients had cognitive deficits including difficulty in areas of attention and executive functioning with pronounced weaknesses in divided and sustained attention (complex attention) set-shifting, speed of processing, and working memory. This was a group of 57 patients who were sent to acute rehabilitation after they were cleared of having active virus. All were debilitated and had a mean age of 64. 75 percent were male, 61 percent non-white and 56 percent were fully employed. In this group 88 % had suffered hypoxic respiratory failure with most being intubated for ventilatory support. 29% went on to get a tracheostomy tube inserted indicating a likely longer-term need for breathing support. 84 % need assistance with activities of daily living, has impaired mobility, and support for IADL’s. Neuropsychology services saw them an average 6.6 days after admission to the rehabilitation hospital. In general, the Whittier cases admitted for covid-recovery were referred to a neuropsychologist within 48 hours of admission. Ventilation-induced hypercapnia has been experimentally shown to lead to cognitive impairment due to acute inflammatory response advancing the cytokine storm and its multi-system impact.
Studies have described long-term risk and short-term risk to cognitive health from the coronavirus. Severe cognitive decline like dementia may be associated with co-occurring illness from anoxia, respiratory failure, blood clots and is associated with more severe disease and chronic long lasting symptoms. These are linked to prolonged risk of systemic inflammatory illness, increased risk of stroke and white matter disease within the brain and even reported cases of acute transverse myelitis (Budson,A, 2021). Budson reported on symptoms in 30-50 percent of people who experienced mild to moderate disease. Zhou et al. described a sample of 29 patients who were assessed 3 weeks after discharge home who were found to have dysfunction in the system of attention – most notably in sustained attention and reaction time. This may be the result of decreased mental endurance, slow processing and fatigue that are reported across several studies reported here. These patients were positively coorlated with C-reactive protein – a marker of the bodies inflammatory response when elevated.
Elevated level of CRP may be a valuable early marker in predicting the possibility of disease progression in non‐severe patients with COVID‐19, which can help health workers to identify those patients an early stage for early treatment.
Nurshad, A 2020
Rampage published in the table below in the American Journal of Speech Pathology in 2020. The long-haul covid-recovered are likened to patients described as having post-intensive care syndrome that occurs as a result of the changes in the system of cognition and emotional regulation. This is one of the best tables I have seen that illustrates the impact of the virus and the systems that are impacted. Rampage et al.
Delirium is another concern and fits in with what is called post-ICU syndrome (PICS), a collection of problems that can present—and linger—after a critical illness. “The three domains we worry about are impairments in physical function, cognitive function, and mental health” .
Yale School of Medicine Carrie MacMillen June 2020
The long term impact may be seen later on in life. Chronic systemic inflammation has been shown to promote cognitive decline and neurodegenerative disease makes it more likely that COVID-19 survivors will experience neurodegeneration in later years that has been known for a long time. Those with short term cognitive consequences may have had less viral load and for a shorter duration of time. Interestingly, those who were in covid-recovery units and on ventilators tended to report less cognitive symptoms suggesting there may have been some protective element to consistent ventilatory or simply timing and getting to the hospital before the hyperinflammatory (cytokine storm) phase of the viral process. A global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus .
Whittier Rehabilitation Hospital in Westborough, MA is looking at the data of 73 patients. This is very likely the first and largest subset of surviving long haul cases of the coronavirus. Our population is older 70.6 years, 66% white males versus approximately 64 years reported in the Italian studies reported here. The Italian samples were largely male as well. The average length of stay was 19.6 days. 21% had signs and symptoms of clinical depression or generalized anxiety co-occurring with their physical and cognitive symptoms. 14% had persistent delirium and encephalopathy.
Recovery from the long-haul symptoms reported in this paper will take weeks to months we predict. It has been recommended that aggressive multidisciplinary rehabilitation be initiated as soon as endurance permits. Intensity shoould include 4-5 times a week PT, OT, and speech language pathology. In many cases the comorbid depression and anxiety must be dealt with concurrent to the restorative physical and cognitive work. Some have likened the neurocognitive impact of covid-19 to that of a moderate traumatic brain injury in the breadth of its impact and tough return to a semblance of normalcy. Aggressive treatment is strongly recommended and should be commensurate with endurance and debility. There is evidence that the likelihood of full return to work is decreased after 6 months or more of recovery.
References
Ferrucci, R et al., (2021) Brain Sci. 11, 235.
Jaywant et al., (2021) Neuropsychopharmacology, 0:1-6
Budson, A. (2021) B.U.Medical School — https://www.health.harvard.edu/blog/author/abudson
Heneka et al. (2020) Alzheimer’s Research & Therapy. Long and Short-term Cognitive Impact of Coronavirus. 12:69 https://doi.org/10.1186/s13195-020-00640-3
Lawton, MP, Brody, EM. (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 9(3): 179-186.
Ramage, A. Potential for Cognitive Communication Impairment in COVID-19 Survivors: A Call to Action for Speech Language Pathologists. Nov. 2020, American Journal of Speech-Language Pathology. Vol. 29. 1821-1832
Sigurvinsdottir, R, Thorisdottir, I, Gylfason, HF. (2020). The Impact of Covid-19 on Mental Health: The role of Locus of Control and Internet Use. International Journal of Environmental Research and Public Health, 17:6985: doi:10.3390/ijerph17196985.
Nurshad, Ali, (2020) J Med Virol. Jun 9 : 10.1002/jmv.26097.
Ludovica Brusaferri, Zeynab Alshelh, Daniel Martins, Minhae Kim, Akila Weerasekera, Hope Housman, Erin J. Morrissey, Paulina C. Knight, Kelly A. Castro-Blanco, Daniel S. Albrecht, Chieh-En Tseng, Nicole R. Zürcher, Eva-Maria Ratai, Oluwaseun Akeju, Meena M. Makary, Ciprian Catana, Nathaniel D. Mercaldo, Nouchine Hadjikhani, Mattia Veronese, Federico Turkheimer, Bruce R. Rosen, Jacob M. Hooker, Marco L. Loggia (2022) The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic, Brain, Behavior, and Immunity, Volume 102, Pages 89-97, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2022.02.018.