Long-term Consequences: Persistent Symptoms Among COVID-19 Survivors

by Margaret Street, Doctor of Pharmacy Candidate and Jamie Wagner, PharmD, BCPS

The COVID-19 pandemic continues to spread as new variants emerge and vaccination uptake has slowed. Globally, COVID-19 has taken an enormous toll on human life. To date, late July 2021, there have been over 190 million cases and more than 4 million deaths.¹ For some COVID-19 survivors, recovery requires only a few days or weeks. Others continue to experience symptoms for months after an initial “recovery.”² These long-lasting symptoms following recovery from the acute infection have commonly been called the post-COVID syndrome or long-haul COVID. The post-COVID syndrome includes new or ongoing symptoms and can impact anyone who was infected with COVID-19, even if the initial infection was asymptomatic. Unfortunately, the long-term consequences of a COVID-19 illness can affect nearly every organ system throughout the body.³ People who are hospitalized with severe illness are more likely to experience post-COVID syndrome, with some studies documenting 70% of patients having at least one persistent symptom following hospitalization.⁴ For less severe illness, an estimated 25-35% of people will have persistent symptoms.^4–6 The symptoms associated with the post-COVID syndrome vary in type and severity, but some are more frequently reported.

A recent systematic review examined the prevalence of persistent COVID-19 symptoms following acute infection.⁴ The review included forty-five studies that followed more than 10,000 patients from 16 different countries. Patients in these studies were a representative mix of males and females (54% male) with a mean or median age younger than 60 years.  The most common comorbidities were diabetes and hypertension. The data suggest that patients younger than 60 years are not protected against post-COVID syndrome. Most patients in these studies were admitted to the hospital which reflects the nature of the underlying studies — 33 of the included studies recruited inpatients only.

The most common persistent symptoms reported by patients were dyspnea, fatigue, anxiety, and cough. Not surprisingly, dyspnea was the most frequently reported symptom following acute recovery.⁴ COVID-19 has been shown to damage the lungs and reduce lung capacity in patients with severe illness.^7–9  The frequency of persistent dyspnea ranged from 7.7%-74.3%  (median 36%) in the included studies. Most studies measured dyspnea by self-report, but some studies used validated measures (e.g., modified Medical Research Council Dyspnea Scale). For those that reported dyspnea prior to COVID-19 infection, a substantial worsening when compared to the patient’s baseline was reported following acute recovery.⁴

Fatigue or exhaustion is another frequently reported symptom among COVID-19 survivors with a reported median frequency of 40% (range: 16.4%-55%). Half of the studies did not specify how fatigue was defined and only 3 studies used validated measurements (e.g., Fatigue Severity Scale, Chalder Fatigue Scale, Patient-Reported Outcomes Measurement Information System Global Health Instrument).⁴ The fatigue reported by COVID-19 survivors appears to mimic the fatigue reported among the survivors of the Severe Acute Respiratory Syndrome (SARS) epidemic in 2003. However, additional long-term monitoring and evaluation is needed in COVID-19 survivors.¹⁰ It is interesting to note that the severity of persistent fatigue symptoms does not appear to correlate with acute illness severity.¹¹ Thus, individuals with very mild acute symptoms may develop severe, persistent fatigue symptoms.

Another common triad of symptoms during the acute COVID-19 illness is cough, atypical chest pain, and fever — all of which may persist for months. Persistent cough after initial recovery was reported in 19 studies, with a frequency ranging from 16.9% to 60%.4 Persistent coughing appears to be more likely in those who were hospitalized, perhaps due to the increased need for respiratory support.¹² Coughing can be disrupting to everyday life and may also lead to social isolation due to social stigma and fear.⁷ Atypical chest pain was reported in 11 studies, with a median frequency among patients of 13.1%; fever was reported in 10 studies but was relatively infrequent with a median of 1% of patients reporting persistent fever.⁴

Anosmia (loss of smell) and ageusia/dysgeusia (loss or distortion of taste) are frequently reported in patients experiencing acute COVID-19 infection and these symptoms can persist throughout the acute illness.⁴ No study included in the systematic review reported patients experiencing new anosmia or ageusia/dysgeusia, only those who had these symptoms at diagnosis. The frequency of persistent anosmia was 23.6% and ageusia/dysgeusia was reported by a median of 15.6% of patients.

Anxiety and depression have also been reported by many people following recovery, particularly those who were hospitalized. Ten studies using standardized evaluation scales for anxiety and depression reported positive symptoms in 22% (median) of patients.⁴ There are several postulated mechanisms why COVID-19 survivors are prone to depression and anxiety.  First, the immune response t0 COVID-19 may contribute directly to psychiatric disorders. Second, the fear of a potentially fatal illness, concerns of infecting others, and social isolation are just a few of the emotional responses that can trigger anxiety and depression. These symptoms have a significant impact on one’s quality of life.^9,13 One study in Spain evaluated the quality of life in people who had been hospitalized from COVID-19 and found that 40% of COVID-19 survivors had a poor quality of life due to psychological symptoms, including anxiety and depression.¹⁴

Changes in cognitive function was reported by 13 studies.⁴ Some of the cognitive changes reported included cognitive deficits, memory loss, and difficulty concentrating.

What remains unknown is how long these symptoms will persist following recovery from acute COVID-19 infection. Survivors of previous coronavirus infections, such as SARS, have also experienced persistent symptoms.¹⁵ Long-term follow-up is needed to determine the persistence and severity of symptoms after a COVID-19 infection. With so many COVID-19 survivors and families burdened by these persistent symptoms, it is important for all of us to inquire about the post-COVID syndrome and address these complaints as best as we can in the years to come.

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