Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19 A Systematic Review
JAMA Netwoh< Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417
Tahmina Nasserie, MPH; Michael Hittle, BS; Steven N. Goodman, MD, MHS, PhD
The horizontal bar extends from the first to the third quartile, the interquartile range (IQR).
The whiskers extend from the upper and lower quartiles to the largest value within 1.5 IQRs of that quartile.
The width of the box represents the IQR.
The vertical bar represents the median value for the outcome.
The circles represent point estimates from each study.
Circles beyond the whiskers are considered outliers.
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Key Points
- Question What are the frequency and variety of persistent symptoms after COVID-19 infection?
- Findings In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%; symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia. However, the studies were highly heterogeneous and needed longer follow-up and more standardized designs.
- Meaning This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health- associated functioning and quality of life; however, methodological improvements are needed to reliably quantify these risks.
IMPORTANCE Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy.
OBJECTIVE To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection.
EVIDENCE REVIEW A search of PubMed and Web ofScience was conducted to identify studies published from January 1, 2020, to March 11,2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, longterm, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study
quality.
FINDINGS A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included inthe systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range IQR, 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity.
CONCLUSIONS AND RELEVANCE This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.
69+ VitaminDWiki pages have LONG-HAUL or LONG-COVID in the title
Items found: 72
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Children who had COVID had 2.2 X higher risk of long COVID if had less than 30 ng of Vitamin D – Jan 2025 |
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30 Jan, 2025 |
Long-COVID reduced some by a small amount of Vitamin D and Vitamin K2 - RCT Jan 2025 |
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16 Jan, 2025 |
Long-COVID and Vitamin D - many studies |
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16 Jan, 2025 |
How vitamin D benefits normal organs and Long-COVID organs – Jan 2025 |
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12 Dec, 2024 |
Brain Plasticity improves the brain, helps Long-COVID - several studies |
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17 Oct, 2024 |
Long-COVID fatigue, anxiety, and cognition treated by 60,000 IU of vitamin D weekly – RCT July 2024 |
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29 Jul, 2024 |
Some early Long-COVID symptoms persist for at least 3 years in US veterans – May 2024 |
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02 Jul, 2024 |
Inflammation causes low iron, which triggers long-COVID – March 2024 |
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04 Apr, 2024 |
Long-COVID 3.1 X more likely if insufficient amounts of Magnesium and Vitamin D – March 2024 |
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24 Mar, 2024 |
Long-COVID a month shorter if more than 20 ng of Vitamin D - Jan 2024 |
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31 Jan, 2024 |
Hypothesis: Both Long COVID and Vaccine Injury are caused by Spike Protein, proposed detox – Nov 2023 |
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24 Nov, 2023 |
Long-COVID: Vitamin D was the only statistically significant factor - Oct 2023 |
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31 Oct, 2023 |
Long COVID with Neuro-Cognitive symptoms had especially low vitamin D levels – Sept 2023 |
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19 Sep, 2023 |
The ONLY Solution to Long COVID (Vitamin D) - video and transcript Sept 2023 |
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12 Sep, 2023 |
Long-COVID can hide in the body for years in scores of locations – Sept 2023 |
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09 Sep, 2023 |
One in five people with long COVID can no longer work (Doctors in this case) - Sept 2023 |
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02 Sep, 2023 |
Number of people with long COVID could be vastly underestimated - Aug 2023 |
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01 Sep, 2023 |
Long-COVID associated with 37 poor genes (no Vitamin D genes) – July 2023 |
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03 Aug, 2023 |
COVID, Long-COVID and Vitamin D in children - Review April 2023 |
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09 Jul, 2023 |
Fasting may reduce inflammation and long-COVID - June 2023 |
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11 Jun, 2023 |
The US believes you have long-COVID if you have more than 12 points (no treatment yet) - May 2023 |
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25 May, 2023 |
COVID, Long COVID, and Vitamin D – May 2023 |
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06 May, 2023 |
2nd COVID infection increases the risk of Long-COVID - 2022 |
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22 Jan, 2023 |
Vitamin D might also help the Long-COVID older adult – Jan 2023 |
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07 Jan, 2023 |
Long-COVID fatigue reduced by Vitamin C and l-Arginine in one month– RCT Nov 2022 |
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24 Nov, 2022 |
Adrenal, Long-COVID and Vitamin D - several studies |
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31 Oct, 2022 |
Long Covid, Short Magnesium - Chambers April 2022 |
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30 Oct, 2022 |
Fatigue and other long-haul problems appear to be associated with low Magnesium - Chambers Oct 2022 |
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30 Oct, 2022 |
Long-COVID symptoms in 10 Percent of women 3 months after infection (22 countries) – Oct 2022 |
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29 Oct, 2022 |
Long-COVID is now the biggest COVID concern - many studies |
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16 Oct, 2022 |
Epstein-Barr Virus probably causes Long-COVID, CFS, and MS - many studies |
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02 Oct, 2022 |
Anti-oxidants and Long-Covid (Mg, Glutamate, Butyrate, etc) – Sept 2022 |
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02 Oct, 2022 |
Chronic Fatigue Syndrome and long-haul COVID-19 |
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26 Sep, 2022 |
Over Two Million Americans Aren’t Working Due to Long-COVID - Aug 2022 |
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27 Aug, 2022 |
Long-COVID: often had not been hospitalized - May 2022 |
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25 Aug, 2022 |
COVID virus persists in most body tissues (Long-COVID) - 2022 |
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23 Aug, 2022 |
Long-COVID in VitaminDWiki |
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16 Aug, 2022 |
LONG-COVID may be permanent in 1 in 200 of people infected – July 2022 |
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06 Aug, 2022 |
Long-Haul more prevalent among seniors - June - 2022 |
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26 Jun, 2022 |
Long-Haul can now be claimed a work disability in the UK – June 2022 |
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24 Jun, 2022 |
Half as much Long-Haul with Omicron - June 2022 |
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19 Jun, 2022 |
Half as much Long-Haul with Omicron - June 2022 |
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19 Jun, 2022 |
COVID Spike persists in Long Haul - June 2022 |
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18 Jun, 2022 |
COVID Long-Haul prevalence increases with time: 50% at 4 months - meta June 2022 |
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17 Jun, 2022 |
COVID and Magnesium - hypothesis, clinical trials, Long-Haul - Oct 2021 |
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10 Jun, 2022 |
Mass disabling events: Polio, WWII, HIV, and COVID Long-Haul - June 2022 |
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06 Jun, 2022 |
1 in 5 Americans who got COVID had Long-Haul for a while - CDC May 2022 |
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27 May, 2022 |
Long-Haul COVID after 3 months – only 5 percent had even 30 ng of Vitamin D – April 2022 |
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04 May, 2022 |
Hypothesis: 2 long-haul COVIDs: had mild symptoms and had needed ICU - April 2022 |
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15 Apr, 2022 |
COVID Long-Haul at 49 weeks: overactive immune system, type O blood - March 2022 |
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07 Apr, 2022 |
Children have less severe COVID, but just as much long-haul as adults - April 2022 |
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06 Apr, 2022 |
Dietary Recommendations for COVID Long-Haul – March 2022 |
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20 Mar, 2022 |
Mild Long-Haul 4.2 X more likely if type O blood - preprint March 16, 2022 |
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20 Mar, 2022 |
Long-Haul COVID is somewhat less of a problem if vaccinated – Nov 2021 |
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18 Mar, 2022 |
COVID long-haul: 1 million in US too sick to work, many cannot get compensation - March 2021 |
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09 Mar, 2022 |
COVID Long-Haul NYT - Feb 2022 |
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19 Feb, 2022 |
COVID Long-Haul fought by probiotics - Jan 2022 |
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29 Jan, 2022 |
COVID Long-Haul predicted by 4 factors (Epstein-Barr virus, etc) – Jan 24, 2022 |
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26 Jan, 2022 |
Some COVID-19 infection become COVID Long-Haul - Nov 2020 |
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15 Dec, 2021 |
Long-haul after breakthrough COVID – Nov 2021 |
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11 Dec, 2021 |
Long-haul, VAERS, Ivermectin, vaccines, etc. Drs. Seheult, Patrick: Video with table of contents - Sept 17, 2021 |
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21 Sep, 2021 |
Your Brain on Covid-19 Long-Haul, Dr. Galland video and transcript - Aug 1, 2021 |
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07 Aug, 2021 |
Long-haul COVID-19 blood tests at Mayo include vitamin D (but no results published) – July 2021 |
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20 Jul, 2021 |
Most people with Long-Haul COVID-19 have low Vitamin D – July 2021 |
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15 Jul, 2021 |
‘Long haul’ COVID rehab worse than cancer rehab, CDC – July 2021 |
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13 Jul, 2021 |
Long-Haul COVID-19 occurred to 1 in 20 who had been asymptomatic (a study of 2 million with COVID-19) – June 2021 |
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15 Jun, 2021 |
COVID-19 Long haul - excellent graph - systematic review May 26, 2021 |
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26 May, 2021 |
COVID-19 vaccines look good in the short term, but probably not good for the long term |
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29 Apr, 2021 |
Long-haul COVID-19 - another hint that Vitamin D should help - Dec 2020 |
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16 Apr, 2021 |
Probably fewer long-haul COVID-19 problems when rejuvenated immune system (Vitamin D, etc.)– Dec 2020 |
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21 Feb, 2021 |
Long-haul fatigue, etc. common after viral infections (SARS1,2, MERS, Swine, 1918,...) |
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21 Feb, 2021 |
Long-distance truck drivers more likely to get COVID-19 (perhaps UVA)- July 2020 |
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12 Aug, 2020 |