Post-COVID-19 Syndrome: Current Evidences and Challenges

Author: PK Gupta

Email: gupta.pk@pharmintel.co.in

Published on 03/Jan/2021

Most people who have coronavirus disease 2019 (COVID-19) recover completely within a few weeks. But some people — even those who had mild versions of the disease — continue to experience symptoms after their initial recovery.

These people sometimes describe themselves as “long haulers” and the condition has been called post-COVID-19 syndrome or “long COVID-19.” The syndrome appears to affect those with mild as well as moderate-to-severe disease. The incidence, natural history and aetiology of these symptoms is currently unknown. Older people and people with many serious medical conditions are the most likely to experience lingering COVID-19 symptoms, but even young, otherwise healthy people can feel unwell for weeks to months after infection. The most common signs and symptoms that linger over time include:

• Fatigue
• Shortness of breath
• Cough
• Joint pain
• Chest pain

Other long-term signs and symptoms may include:

• Muscle pain or headache
• Fast or pounding heartbeat
• Loss of smell or taste
• Memory, concentration or sleep problems
• Rash or hair loss

Possible mechanism of long-term complications:

Although COVID-19 is seen as a disease that primarily affects the lungs, it can damage many other organs as well. This organ damage may increase the risk of long-term health problems. Organs that may be affected by COVID-19 include:

Lungs: People who have experienced COVID-19 pneumonia can have long-standing damage to the tiny air sacs (alveoli) in the lungs. The resulting scar tissue can lead to long-term breathing problems.

Heart: Imaging tests taken months after recovery from COVID-19 have shown lasting damage to the heart muscle, even in people who experienced only mild COVID-19 symptoms. This may increase the risk of heart complications in the future.

COVID-19 can make blood cells more likely to clump up and form clots. While large clots can cause heart attacks and strokes, much of the heart damage caused by COVID-19 is believed to stem from very small clots that block tiny blood vessels (capillaries) in the heart muscle.

Other parts of the body affected by blood clots include the lungs, legs, liver and kidneys.

Current studies/evidences for post COVID-19 syndrome:

1. In first study (Conducted in France by Carvalho-Schneider et al, October 2020): a follow-up was done for 150 adults with non-critical COVID-19 two months after symptoms’ onset. Follow up was done on days 7, 30 and 60. The mean age was 49 years. More than half of the patients (54%, n=80/150) had at least one comorbid condition. The most common symptoms at disease onset were flu-like symptoms (87%, n=129/150), anosmia/ageusia (59%, n=89/150) and fever (51%, n=76/150). Overall, in this descriptive clinical follow-up study of 150 non-critical patients with COVID-19, two-thirds of adults experienced persistent symptoms up to 2 months after symptom onset, primarily anosmia/ageusia, dyspnea or asthenia.
2. In second study (Conducted in France by Garrigues et al, August 2020): a follow-up was done for 120 adults who are experiencing post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. The mean age was 63.2 and 62.5% were male. The most common comorbidities included hypertension (46.7%), an elevated body mass index (47.5%) and diabetes (21.7%). The mean time of interview after admission was 110 days. The most common reported symptoms were fatigue (55%), dyspnea (42%), memory loss (34%), sleep disorders (30.8%) and difficulty with concentration (28%). Comparisons between ICU and non-ICU patients showed no statistically significant differences regarding these symptoms. Overall, in this study of patients with COVID-19 discharged from the hospital and interviewed over 3 months post diagnosis, the majority of patients experienced continued symptoms, most commonly including fatigue and dyspnea.
3. In third study (Conducted in Italy by Carfi, July 2020): follow-up of 143 adults who are experiencing Persistent symptoms after acute COVID-19. The mean age was 56.5 years. 53 (37%) were women. 10% were active smokers. The most common comorbidity was hypertension (35%), followed by thyroid disease (18%), immune disorders (11%), COPD (9%) and diabetes (7%); rates of other comorbidities were less than 5%. 63% engaged in regular physical activity prior to admission. 7% of participants had evidence of interstitial pneumonia during their hospitalization, and 54% required oxygen therapy. Mean length of hospital stay was 13.5 days. 21 patients (15%) received non-invasive ventilation; 7 patients (5%) received invasive ventilation. Patients were assessed a mean 60.3 days after onset of the first COVID-19 symptom. 87% of patients had persistent symptoms. 32% had 1 or 2 persistent symptoms, while 55% had 3 or more persistent symptoms. Most common reported symptoms were fatigue (53%), dyspnea (43%), arthralgias (27%) and chest pain (22%). 1% of patients reported a worsened quality of life. Overall, in this study of patients with COVID-19 discharged from the hospital with SARS-CoV-2 RNA clearance by RT-PCR and interviewed approximately 2 months after diagnosis, the majority of patients experienced continued symptoms, with the most common symptoms being fatigue and dyspnea.
4. In fourth study (Conducted in UK by Halpin et al, July 2020): follow-up of 100 adults who are experiencing Persistent symptoms after acute COVID-19. Telephone survey study of 100 patients with COVID-19 discharged from the hospital at least 4 weeks prior to study enrolment; 32 patients had been in the ICU. The median age of the patients was 58.5 in the ICU group and 70.5 in the non-ICU group. 7% required some form of oxygenation support. 4% of patients in the ICU group and 51.5% of the non-ICU group were men. The most common comorbidity was hypertension (43.8% in the ICU group and 39.7% in the non-ICU group). Other common comorbidities were being overweight or obese (35% in the ICU group, 54.4% in the non-ICU group), type 2 diabetes (28.1% in the ICU group, 27.9% in the non-ICU group) and gastrointestinal disease (15.6% in the ICU group, 29.4% in the non-ICU group). 3% of patients in the ICU group and 70.6% in the non-ICU group had 3 or more significant comorbidities. Patients were interviewed between 29 and 71 days (mean 48 days) post-discharge. New fatigue was the most common reported symptom. 72% of participants in the ICU group reported fatigue, while 60.3% in the non-ICU group did. The next most common symptoms were dyspnea (65.6% in the ICU group and 42.6% in the non-ICU group) and psychological distress (46.9% in the ICU group and 23.5% in the non-ICU group). 8% of patients in the ICU group and 45.6% in the non-ICU group reported a decline in their health status, as measured by the EQ-5D. Overall, in this study of patients with COVID-19 discharged from the hospital at least 4 weeks prior to study enrolment, the majority of patients experienced continued symptoms, with the most common symptoms being fatigue and dyspnea.
5. In fifth study (Conducted in US by Tenforde, July 2020): A multi-state telephone interview study of a random sample of 274 patients with a positive SARS-CoV-2 RT-PCR test at an outpatient visit at one of 14 academic centers in 13 U.S. The median time between the outpatient visit and the interview was 16 days. The median age of symptomatic respondents was 42.5 years; 142 (52%) were female. Most common symptoms included cough (43%), fatigue (35%) and dyspnea (29%). Among patients ≥50 years of age, 47% reported not having returned to their usual state of health. 57% of patients with ≥3 chronic conditions reported not having returned to their baseline state of health. Overall, in this study of patients who were diagnosed with COVID-19 in the outpatient setting, primarily had mild disease and were interviewed a median of 16 days post diagnosis, the majority had continued symptoms. The most common symptoms included cough and fatigue.

Conclusion:

Based on current evidences, it is evident that majority of the patients were experiencing few of the COVID-19 symptoms especially fatigue, dyspnea, cough, asthenia, arthralgia etc. post recovery from virus and in majority of the cases persistence of the symptoms can be explained on the basis of long-term changes in organ functions especially in lungs.

For physicians, who are treating patients with post-COVID-19 symptoms, it is become mandatory to understand the pathophysiology of these symptoms and design the treatment protocol accordingly based on patient’s overall health status.

References

• https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351
• https://www.idsociety.org/covid-19-real-time-learning-network/disease-manifestations–complications/post-covid-syndrome/