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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 .
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 . 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 . 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 . 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 . About one-third of hospitalized patients develop ocular abnormalities including conjunctivitis . 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 .
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 . 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.
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 . Some patients who recover from COVID-19 develop mental health problems . 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 . 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 . They have physical, cognitive, and mental health problems. Covid-19 recovery units are being designed for these patients . 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 . 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 . 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.
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