Effect of COVID-19 Throughout the Body: Part II

  • Jain, Uday, MD
| Sep 21, 2020

To read Part 1, click here. 

Effect on Brain

ACE2 receptors are present in the cerebral cortex and brain stem. Some patients have meningitis and encephalitis indicating viral invasion of the central nervous system (CNS). There is depression of brain stem reflexes including the one that senses oxygen starvation. Neurological manifestations may be the only ones observed or may occur in combination with respiratory or other symptoms [45-47]. Neurological manifestations are more common in people with more severe disease. Altered oxygen and carbon dioxide levels may contribute to them. They include dizziness, headache, impaired consciousness including confusion, delirium, and inability to rouse. Delirium is common and can lead to long-term cognitive impairment including memory deficits. Because of a shortage of commonly used sedatives like propofol and dexmedetomidine, benzodiazepines are being used for sedation. They can enhance delirium. Brains of dead patients demonstrate hypoxic changes but not encephalitis or other changes due to the virus [48].

Cytokine storm can cause brain inflammation and edema. Some patients have sympathetic storm that can cause seizure like symptoms. Stroke due to blockage of a cerebral artery can occur even in young patients with no prior history [49]. This is in part because of hypercoagulability and endothelial injury. Cerebral hemorrhage is also observed. Ataxia and seizure may be present. Cranial nerves involvement may occur.

Anosmia and dysgeusia, i.e., impaired sense of taste, are reported [50]. Nerve pain, skeletal muscle weakness and pain, tingling or numbness in the hands and feet are also observed. Rhabdomyolysis may cause elevated serum creatine kinase. Neurologic features among patients in intensive care unit (ICU) with ARDS included encephalopathy, agitation, and confusion [45]. Corticospinal tract

signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes are present in most of the patients.

Effect on Eyes

Both ACE2 receptors and TMPRSS2 proteases that are necessary for infection by SARS-CoV-2 are found in ocular surface cells in cornea, inside the eyelids and in the white of the eye [51]. About one-third of hospitalized patients develop ocular abnormalities including conjunctivitis [52]. Conjunctivitis is more common in the sicker patients. Ocular involvement may occur early. Ocular surface cells are portals of entry and reservoirs of the virus. Ocular virus shedding is a source of infection. Infectious virus can persist in the eye for up to three weeks [53].

Gastrointestinal Effect

Gastrointestinal (GI) symptoms include loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort [54, 55]. These symptoms might start before or occur with or without other symptoms such as fever, myalgias, and cough. Lower gastrointestinal tract is rich in ACE2 receptors. Some patients’ stool contains intact infectious virus or only RNA and protein fragments of the virus. Patients who have virus in the stool take longer to clear it. Although a small percentage of patients have GI symptoms, up to one- half shed virus in the stool [55]. Virus protein shell is also found in gastric, duodenal, and rectal cells. More than one half of COVID-19 hospitalized patients have elevated lactate dehydrogenase and other liver enzymes indicating injury to the liver or bile ducts. This is likely to be due to an overactive immune system or due to drugs causing liver damage.

Effect on Skin

Skin manifestations of COVID-19 are similar to those of other viruses and chronic inflammatory diseases like acne, eczema, psoriasis, and rosacea. Vascular problems associated with skin manifestations can be neurogenic, microthrombotic, or immune complex mediated. Of the patients with skin manifestations, a majority have patchy erythematous rash [56,57]. Some have widespread urticaria or hives. A few also have chickenpox-like fluid-filled vesicles or blisters. They can have measles-like rashes. The most commonly affected area is the trunk. Itching is mild or absent. Some patients have skin eruptions at symptom onset, and others after hospitalization. Lesions usually heal in a few days. Skin manifestations do not correlate with the severity of COVID-19.

Patients may develop livedo reticularis. It is a purplish net-like discoloration of the skin, often a result of blood clotting abnormalities. Lacy, dusky rashes, including dead skin cells are observed on the arms, legs, and buttocks. They are associated with hypercoagulability. Petechiae are present. Nonpruritic blanching livedoid vascular eruption, possibly due to vaso-occlusion may be present. They appear as mottled, net- like red or pink patches. Also present are chilblains, which are purplish, slightly firm and often tender. COVID toes and fingers have frostbite-like areas with red or purple rash or hive-like eruption.

Psychological Effects

Because of financial difficulties and social isolation due to COVID-19, many psychological problems can arise. They can be delayed by months. There is an increase in "deaths of despair" from substance abuse or suicide. The risk is greater among persons with dementia, mental illness, and autism. Online communication with friends and support professionals are beneficial.

On discharge from ICU, a third of the patients have dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command [45]. Some patients who recover from COVID-19 develop mental health problems [58]. These include anxiety, depression, and post-traumatic stress disorder (PTSD). Long term effects can include development of Alzheimer’s or Parkinson’s disease.

Providers may also develop mental health problems [59-60]. They may face social stigma as potential vectors of infection [59]. Some providers may indulge in self- stigmatization. They may distance themselves from family members and others to avoid infecting them. Some providers worry about losing their income if they get infected. The need for support for the providers is being recognized [59-60].


Compared to other patients on mechanical ventilation, COVID-19 patients usually require it for longer durations of two or more weeks. Some patients suffer from pulmonary scarring that can cause long-term respiratory problems. Those who leave the ICU may suffer from post-intensive care syndrome [61]. They have physical, cognitive, and mental health problems. Covid-19 recovery units are being designed for these patients [62]. Patients who are well enough to leave the ICU or the hospital, many still have the virus and test positive for it. They may have to wait until they’re not contagious to get in-home care or be able to visit a rehab facility.

Survivors of ARDS can develop a disorder that is characterized by muscle atrophy, persistent fatigue, weakness, and limited exercise tolerance [63]. This limited exercise tolerance is in part related to the use of systemic corticosteroids to treat the disease and multiorgan dysfunction during the ICU stay. COVID-19 survivors have PTSD, chronic pain, muscle atrophy, widespread inflammation, sleep disorders, fibromyalgia, and fatigue [63]. Chronic disorders may emerge long after acute recovery. Disability may occur. The rights of the disabled should be respected [64,65].

Effect on Children

Compared to adults, most of the children are less susceptible to COVID-19 and tend to have milder disease. However, a small number of them develop multisystem inflammatory syndrome in children (MIS-C) [66-70]. The syndrome is usually delayed one to two months after acute infection with COVID-19.

The patients have symptoms similar to those in Kawasaki disease and toxic shock syndrome. Most but not all of them are positive for antibody tests for SARS-CoV-2. Many are positive for antigen test. Patients may have high fever, rash, and enlarged lymph nodes. Many have gastrointestinal symptoms. Cardiac effects include inflammation and dilation of coronary arteries, myocarditis, and rhythm disturbance. Respiratory symptoms are less common. There is marked elevation of inflammatory markers including C reactive protein and serum interleukin-6. Although the children become critically ill, mortality is low.


45.Helms J, Kremer S, Merdji H, et al.: Neurologic Features in Severe SARS-CoV-2

Infection. N Engl J Med. 2020, 10.1056/NEJMc2008597

46.Lahiri D, Ardila A: COVID-19 Pandemic A Neurological Perspective. Cureus.

2020, 10.7759/cureus.7889

47.Mao L, Jin H, Wang M, et al.: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol.

2020, 10.1001/jamaneurol.2020.1127

48.Solomon I, Normandin E, Bhattacharyya S, et al.: Neuropathological Features of Covid-19. N Engl J Med. 2020, 10.1056/NEJMc2019373

49.Oxley T, Mocco J, Majidi S, et al.: Large-Vessel Stroke as a Presenting Feature

of Covid-19 in the Young. N Engl J Med. 2020, 10.1056/NEJMc200978712

50.Spinato G, Fabbris C, Polesel J, et al.: Alterations in Smell or Taste in Mildly

Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA.

2020, 10.1001/jama.2020.6771

51.Zhou L, Xu Z, Castiglione G, et al.: ACE2 and TMPRSS2 are expressed on the

human ocular surface, suggesting susceptibility to SARS-CoV-2 infection.

BioRxiv. 2020, 10.1101/2020.05.09.086165

52.Wu P, Duan F, Luo C, et al.: Characteristics of Ocular Findings of Patients With

Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA

Ophthalmol. 2020, 10.1001/jamaophthalmol.2020.1291

53.Colavita F, Lapa D, Carletti F, et al.: SARS-CoV-2 Isolation From Ocular

Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA

Detection.. Ann Intern Med. 2020, 10.7326/M20-1176

54.Han C, Duan C, Zhang S, et al.: Digestive Symptoms in COVID-19 Patients with

Mild Disease Severity. Clinical Presentation, Stool Viral RNA Testing, and

Outcomes. Am J Gastroenterol. 2020, 10.14309/ajg.0000000000000664

55.Parasa S, Desai M, Chandrasekar V, et al.: Prevalence of Gastrointestinal

Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019.

A Systematic Review and Meta-analysis. JAMA. 2020, 10.1001/jamanetworkopen.2020.11335

56.Darlenski R, Tsankov N: Covid-19 pandemic and the skin - What should

dermatologists know?. Clin Dermatol. 2020, 10.1016/j.clindermatol.2020.03.012

57.Recalcati S: Cutaneous manifestations in COVID‐ 19: a first perspective. J Eur

Acad Dermatol. 2020, 10.1111/jdv.16387

58.Pfefferbaum B, North C: Mental Health and the Covid-19 Pandemic. N Engl J

Med. 2020, 10.1056/NEJMp2008017

59.Dzau V, Kirch D, Nasca T: Preventing a Parallel Pandemic — A National

Strategy to Protect Clinicians’ Well-Being. N Engl J Med.

2020, 10.1056/NEJMp2011027

60.Creating Wellness in a Pandemic: A Practical Framework for Health Systems

Responding to Covid-19. (2020). Accessed: 06/28/20 https://catalyst.nejm.org/doi/full/10.1056/CAT.20.0218.

61.For survivors of severe COVID-19, beating the virus is just the beginning. (2020). Accessed: 06/20/20: https://www.sciencemag.org/news/2020/04/survivorssevere-covid-19-beating-virus-just-beginning.

62.A Paradigm for the Pandemic: A Covid-19 Recovery Unit. (2020). Accessed:

06/28/20: https://catalyst.nejm.org/doi/full/10.1056/cat.20.0238.

63.Vittori A, Lerman J, Cascella M: COVID-19 Pandemic ARDS Survivors: Pain after

the Storm?. Anesth Analg. 2020, 10.1213/ANE.0000000000004914

64.Mello M, Persad G, White D: Respecting Disability Rights — Toward Improved

Crisis Standards of Care. N Engl J Med. 2020, 10.1056/NEJMp2011997

65.Solomon M, Wynia M, Gostin L: Covid-19 Crisis Triage — Optimizing Health

Outcomes and Disability Rights. N Engl J Med. 2020, 10.1056/NEJMp2008300

66.Riphagen S, Gomez X, Gonzalez-Martinez C, et al.: Hyperinflammatory shock in

children during COVID-19 pandemic. Lancet. 2020, 395:1607-

1608. 10.1016/S0140-6736(20)31094-113

67.Whittaker E, Bamford A, Kenny J, et al.: Clinical Characteristics of 58 Children

With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated

With SARS-CoV-2. JAMA. 2020, 10.1001/jama.2020.10369

68.Cheung E, Zachariah P, Gorelik M, et al.: Multisystem Inflammatory Syndrome

Related to COVID-19 in Previously Healthy Children and Adolescents in New

York City. JAMA. 2020, 10.1001/jama.2020.10374

69.Son M: Pediatric inflammatory syndrome temporally related to covid-19. BMJ.

2020, 10.1136/bmj.m2123

70.Toubiana J, Poirault C, Corsia A: Kawasaki-like multisystem inflammatory

syndrome in children during the covid-19 pandemic in Paris, France: prospective

observational study. BMJ. 2020, 10.1136/bmj.m2094

Leave a comment