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It’s All in The Name, Or Is It: The Characterization of “Long COVID”

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As scientific progress is made to understand further the SARS-CoV-2 virus, there remain many unanswered questions about the virus and its long-term effects on the human body and human psyches. Long-COVID, as a stand-alone subject within the current pandemic, is perhaps difficult to limit to one short article. This two-part piece will examine the characterization of long COVID and other associated terms used in addition to its overall impact on those who survive the infection. The impact portion will explore mental health, employment and complications experienced post-infection.  

As we mark the end of 2021 and celebrate the start of 2022, the COVID-19 pandemic continues to strain health care systems around the world. Science and medicine have learned much about the SARS-CoV-2 virus since the onset of the pandemic. We now know that the incubation period for the virus is said to be approximately 4 to 5 days [1]. According to Ahmad et al. (2021), the World Health Organization has noted that most positive COVID-19 cases – roughly 80 to 85 % clinically manifest a mild or asymptomatic form and may resolve within two weeks of onset. The primary symptoms have been noted to be fever, sore throat, cough, headache, myalgia, anosmia and diarrhea [1]. A severe increase in disease reported to last approximately six weeks has been observed in 10 to 15% of cases, requiring hospitalization and supplemental oxygen therapy [1]. Critical illness is said to occur in 5% of the affected population. The virus affects their lungs and brings about multi-organ dysfunction, requiring ICU admission and subsequent mechanical ventilation [1].

While most positive COVID-19 cases have been reported to completely resolve in 3 to 4 weeks after the onset of infection, many individuals continue to experience symptoms for weeks or months following the start of the disease. This aspect of COVID-19 has continued to fuel debate and challenge what is known about “long COVID” [1,2]. Many experts appear to agree that persistent COVID-19 symptoms lasting longer than 30 days or more with the prevalence of individual symptoms are the fundamental characterizations of post-acute sequelae of COVID-19 or PASC for short [2]. Debate continues in the scientific community concerning developing a more specific time frame characteristic, breaking down the classification of post-COVID-19 infections even further. Fernández-de-Las-Peñas et al. (2021) suggest the following time frame characterization:

  • Potentially infection-related symptoms – up to 4 to 5 weeks
  • Acute post-COVID symptoms – 5 to 12 weeks
  • Long post-COVID symptoms – 12 to 24 weeks
  • Persistent post-COVID symptoms – more than 24 weeks[3]

The understanding of PASC is evolving, understanding the diagnoses, phenotypes, and epidemiology is promising. Most research regarding PASC to date has centred around hospitalized COVID-19 patients. However, Bell et al. (2021) note that most individuals with COVID-19 end up not being hospitalized, leading to PASC being poorly characterized in this COVID-19 population subset [2]. Bell et al. (2021) conducted the CoVHORT study from a diverse population-based group of Arizonans to estimate the prevalence of PASC. As of February 24, 2021, the study comprised 3,468 participants who were subject to a positive PCR or antigen and subsequently were not hospitalized for their illness. The study excluded participants who had incomplete COVID-19 testing data, leaving 543 participants to receive a follow-up survey. Bell et al. (2021) note that 303 (55.8%) of the 543 participants completed the follow-up survey [2]. The group had a mean age of 44 years and ranged from 12 to 82; 70% were female, while non-Hispanic whites consisted of 68% of participants. 38% of the group had a college or higher form of education. 67% of the group reported a pre-existing chronic condition, consisting of 42% reporting seasonal allergies, 16% reporting asthma and 15% reporting hypertension [2]. In contrast, females were more likely to experience PASC than males, 73% versus 63%; Bell et al. (2021) highlight that this finding did not reach the statistical significance threshold with a p-value of 0.07 [2].

The follow-up conducted at 30 days and greater consisted of 208 of 303 participants (68.7 %, 95% CI: 63.4, 73.9) reporting experiencing PASC. The median number of symptoms reported by these individuals experiencing PASC was noted to be 3 with a range of 1 to 20. A median follow-up of 63 days with 30 to 250 days [2]. At 30 days or greater, the ten most common symptoms noted by Bell et al. (2021) were:

  • Fatigue (37.5%)
  • Shortness of breath (37.5%)
  • Brain fog (30.8%)
  • Stress/anxiety (30.8%)
  • Altered taste or smell (26.4%)
  • Body aches or muscle pain (26.0%)
  • Insomnia (22.1%)
  • Headaches (20.7%)
  • Joint pain (20.2%)
  • Congestion or runny nose (19.2%)[2]

Participants who were followed for 30 to 59 days post-diagnosis, 87 (59.6%, 95% CI: 51.6, 67.5) of them reported experiencing PASC, while 121 participants (77.1% 95% CI: 70.5, 83.6) who were followed for more than 60 days reported experiencing PASC. While the frequency of symptoms was observed to be higher at longer follow-up, prevalent symptoms appeared to be similar, such as fatigue, shortness of breath, and brain fog [2]. Additionally, Bell et al. (2021) found that only 6 participants reported stress/anxiety as their sole symptom, demonstrating that this non-specific symptom was not a driver of PASC prevalence in their study.

Those without follow-up data, when compared to eligible participants with follow-up data, were found to be younger, 39 years versus 44, more likely to be male – 37 versus 30%, be of Hispanic ethnicity – 32 versus 23%, more likely to smoke or vape – 25 versus 13% and possess a lower level of education – 60 versus 72% who had completed college. Lastly, disease severity ratings were similar also – 4.9 versus 4.7 out of 10 in addition to rates of pre-existing conditions – 64 versus 70% [2].

The prevalence of PASC among other studies has been similar. For instance, Huang et al. (2021) noted a majority of 76% at six months. Carfì et al. (2020) found a prevalence of 87% at two months, while Lopez-Leon et al. (2021) noted a PASC prevalence of 80% through a systematic review of 7 studies examining mixed follow-up and severity of both hospitalized and non-hospitalized patients [2]. Other notable studies examining PASC prevalence include:

  • Logue et al. (2021) – reported a prevalence of 33% among outpatients – the lower prevalence rate may be due to a longer follow-up time of 169 days.
  • Haverall et al. (2021) – reported an estimated prevalence of 26% amongst mild cases
  • Sudre et al. (2021) – reported 13% in a mixed-severity group

Bell et al. (2021) noted that a large study utilizing Veteran Administration electronic health records reported an “increased risk of death, morbidity, health resource utilization, and medication use” among those who survived at least 30 days following their COVID-19 diagnosis [2]. The lower prevalence rate of PASC in Al-ly, Xie & Bowe (2021) may partly be due to their use of electronic health records compared to Bell et al. (2021).

Patients experiencing PASC also appear to suffer in terms of quality of life. Aiyegbusi et al. (2021) cited multiple studies that used the generic EuroQol Five Dimension (EQ-5D) index score, the EuroQol Visual Analog Scale (EQ-VAS), the RAND Short Form-36 questionnaire (SF-36) and the PROMIS Global Health instrument in determining the level of impact on quality of life. Evidence suggests that individuals experiencing PASC suffer a significant reduction in quality of life [4]. According to Aiyegnusi et al. (2021), the work of Weerahandi et al. (2021) considered the quality of life between a 4-to-12-week follow-up. It examined previously hospitalized patients with COVID-19 in the United States. They found that scores on the PROMIS Global Health-10 instrument revealed worse general health following acute illness than baseline. While patients’ summary scores in the physical and mental health domains were slightly above the US mean at baseline, patients did report a reduced ability to carry out social activities 4 to 6 weeks after being hospitalized [4]. Moreno-Perez et al. (2021) comparison of EQVAS scores showed a significant difference in overall quality of life in patients noted to have ongoing symptoms and those who reported no symptoms following acute infection at 10 to 14 weeks of follow-up (43.2% versus 66.9%, p = 0.0001) [5]. Aiyegbusi et al. (2021) further noted that another study consisting of a six-month follow-up of previously hospitalized patients revealed an overall EQVAS score of 80%, indicating persistent reductions in quality of life [4]. The study of previously hospitalized patients with COVID-19-related ARDS revealed that 61 out of 91 individuals (67%) experienced a decrease in their quality of life six months post-infection. Comparing their EQ-5D index and their EQ-VAS scores before acute infection and six months post-infection underscored a significant difference in the quality of life. (EQ-5D Index 0.965 pre- and 0.705 post-infection, p<0.001) and EQ-VAS 87.6% pre- and 66.4% post-infection, p<0.001) [4]. Analogously, significant impairment in functional status was noted among these patients; 30.8% reported no limitation in their daily activities; the findings were based on the Post-COVID-19 Functional Status scale. A further study highlighted by Aiyegbusi et al. (2021) noted that 72% (28/39) of individuals who regularly engaged in sports before hospitalization due to COVID-19 were able to resume physical activity after three months. Nearly half of those could only do so at a lower intensity [4].

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Acknowledgement

I would like to thank Dr. Jeff Jarvis, MD, EMT-P, for his participation in providing some of the articles used for this piece. Dr. Jarvis is one of the hosts of the EMS Lighthouse Project podcast, the Medical Director for Williamson County EMS and Marble Falls Area EMS, and a practicing emergency physician at Baylor Scott & White Hospital in Round Rock, Texas.

References

  1. Ahmad MS, Shaik RA, Ahmad RK, Yusuf M, Khan M, Almutairi AB, et al. “LONG COVID”: an insight. European review for medical and pharmacological sciences [Internet]. 2021 Sep [cited 2022 January 4];25(17):5561–77. Available from: https://pubmed.ncbi.nlm.nih.gov/34533807/
  2. Bell ML, Catalfamo CJ, Farland LV, Ernst KC, Jacobs ET, Klimentidis YC, et al. Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona cohort. PLOS ONE. 2021;16(8):1–7.
  3. Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. International journal of environmental research and public health [Internet]. 2021 Mar 5 [cited 2022 Jan 5];18(5). Available from: https://pubmed.ncbi.nlm.nih.gov/33807869/
  4. Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, et al. Symptoms, complications and management of Long Covid: A Review. Journal of the Royal Society of Medicine. 2021;114(9):428–42.
  5. Moreno-Pérez O, Merino E, Leon-Ramirez J-M, Andres M, Ramos JM, Arenas-Jiménez J, et al. Post-acute covid-19 syndrome. incidence and risk factors: A Mediterranean cohort study. Journal of Infection. 2021;82(3):378–83.
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