Long COVID Chart Jan23

Last update: Thursday 3/9/23 

“Data!data!data!" he cried impatiently. "I can't make bricks without clay." ― Arthur Conan Doyle, The Adventure of the Copper Beeches - a Sherlock Holmes Short Story

This reference page provides links to recent large scale studies of long COVID and a chart that is designed to help our readers identify the most important findings on which these studies seem to agree or disagree. Large studies are its focus because long COVID's wide range of debilitating symptoms will probably need huge amounts of data to resolve. Links to background info about long COVID and smaller scale studies can be found HERE

Note: Please wait for a few seconds until the large chart downloads from the Google cloud before scrolling through its rows and columns.

... Under continuing reconstruction ... 

A. Links | B. Chart

Rationale for the selections of the large-scale studies

As of March 8, 2023, the editor of this blog had selected 20 large-scale studies. Nineteen had appeared in peer reviewed journals plus one oft-cited pre-print by authors who had published five of the 19 peer reviewed articles. To date, only 13 of these studies have been added to the chart because the editor paused to take time to formulate a more explicit rationale for why these particular studies had been selected.

The editor is a data scientist and a policy analyst; he is neither a medical researcher nor a bioscientist. Therefore he is not qualified to assess articles that examine the  biological processes underlying the varied manifestations of long COVID. That's why he selected articles that shed light on questions that policy makers and ordinary citizens have often asked. 

1. What percentage of those who were infected with COVID will be left with long COVID, i.e., will not fully recover within one month, three months, one year, two or or more years thereafter?

2. What are the risk factors most often associated with long COVID, i.e., who is most likely to be a COVID survivor who does not fully recover from their initial infection?

3. Are the vaccines, other preventions, and treatments that reduce the severity of initial COVID infections also associated with reductions in the severity and/or duration of long COVID?

4. Is the severity of initial COVID infections associated with the severity and/or duration of long COVID?

5. What kinds of long COVID have the longest recovery times?

A. Links to 13 large scale studies
Where possible, supplementary links to shorter TL;DR summaries of the large studies that were published in reputable media are also provided. 

1. "Long-term cardiovascular outcomes of COVID-19", Yan Xie, Evan Xu, Benjamin Bowe & Ziyad Al-Aly, Nature Medicine, 2/7/22
   -- "Heart-disease risk soars after COVID — even with a mild case", Saima May Sidik, Nature, 2/10/22
   
   
2. "Risks and burdens of incident diabetes in long COVID: a cohort study", Yan Xie and Ziyad Al-Aly, The Lancet, 3/22/22
   -- "Diabetes risk rises after COVID, massive study finds", Clare Watson, Nature, 3/31/22
   
   
3. "Post–COVID Conditions Among Adult COVID-19 Survivors Aged 18–64 and ≥65 Years — United States, March 2020–November 2021", Lara Bull-Otterson, Sarah Baca1, Sharon Saydah,  et al., CDC, 5/24/22 
   -- "More than 1 in 5 adult Covid survivors in the U.S. may develop long Covid, a C.D.C. study suggests.", Pam Belluck, NY Times, 5/24/22
   
   
4. "Long COVID after breakthrough SARS-CoV-2 infection", Ziyad Al-Aly, Benjamin Bowe & Yan Xie, Nature Medicine, 5/25/22
   -- "Long COVID risk falls only slightly after vaccination, huge study shows", Sara Reardon, Nature, 5/25/22
   
   
5. "Reduced Incidence of Long Coronavirus Disease Referrals to the Cambridge University Teaching Hospital Long Coronavirus Disease Clinic ", Benjamin A Krishna, Marina Metaxaki, Mark R Wills, Nyaradzai Sithole, Clinical Infectious Diseases, 8/1/22
   -- "Referrals to long COVID clinic fell by 79% following roll-out of the vaccine", University of Cambridge, Craig Brierley, 10/6/22
   
   
6. "Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021", Global Burden of Disease Long COVID Collaborators, JAMA Network, 10/10/22
   -- "Long Covid Disables Millions Worldwide, Even as Rates Ease, Study Shows", Jason Gale, Bloomberg via MSN, 10/10/22
   --  "Long COVID stemmed from mild cases of COVID-19 in most people, according to a new multicountry study", Sarah Wulf Hanson and Theo Vos, The Conversation, 1/5/23
   
   
7. "Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study", Claire E. Hastie and associates, Nature Communications, 10/12/22
   -- "Large study provides powerful evidence of long covid’s lasting impact", Frances Stead Sellers, Washington Post, 10/12/22
   -- "Nearly Half of Covid Patients Haven’t Fully Recovered Months Later, Study Finds", Benjamin Mueller, NY Times, 10/12/22
   
   
8. Executive summary of "Prevalence of post COVID-19 condition symptoms: a systematic review and meta-analysis of cohort study data, stratified by recruitment setting", European Centre for Disease Prevention and Control (ECDC), 10/31/22 ... PDF of full report found ==> HERE
   -- "More severe COVID-19 may raise risk of long COVID", Stephanie Soucheray, CIDRAP, 10/31/22
   
   
9. "Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19", Yan Xie, Taeyoung Choi, and Ziyad Al-Aly, medRxiv, 11/5/22
   -- "Paxlovid May Reduce Risk of Long Covid in Eligible Patients, Study Finds", Pam Belluck, NY Times, 11/7/22
   -- Note: "Nirmatrelvir" is Paxlovid.
   -- Note: This report is a preprint, i.e., it has not been accepted for publication by a peer review journal. It has been included in this note because its authors produced three of the studies already included in the note; that's why so the editor of this blog is confident that it will be published in a high prestige journal as soon as possible.
   
   
10. "Acute and postacute sequelae associated with SARS-CoV-2 reinfection", Benjamin Bowe, Yan Xie & Ziyad Al-Aly, Nature Medicine, 11/10/22
    -- "Repeat COVID-19 infections riskier than first bout with virus, study finds", Nancy Lapid, CTV News, 11/11/22 ...This news article contains an incisive comment that should apply to all of the massive Veterans Administration data studies produced by this prolific team ==> "Experts not involved with the study said the VA population does not reflect the general population. Patients at VA health facilities are generally older, sicker people and often men, a group that would typically have more than normal health complications, said John Moore, a professor of microbiology and immunology at Weill Cornell Medical College in New York." ... However ==> "Older" is not really a problem given that upwards of 80 percent of COVID deaths recently have been in oldest age groups
    
    
11. "Prevalence and Correlates of Long COVID Symptoms Among US Adults", Roy H. Perlis, MD, MSc1,2; Mauricio Santillana, PhD3; Katherine Ognyanova, PhD4; et al, JAMA Network Open, 10/27/22
    --"An estimated 15% of U.S. adults infected with SARS-CoV-2 have long-COVID", Pooja Toshniwal Paharia, News Medical, 10/30/22
    
    
12. "Cardiovascular disease and mortality sequelae of COVID- 19 in the UK Biobank", Zahra Raisi- Estabragh et al., BMJ,  8/8/22
    -- "People who caught mild Covid had increased risk of blood clots, British study finds", Spencer Kimball, CNBC, 10/25/22
    
    
13. "Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study", Barak Mizrahi et al., BMJ, 1/11/23
    -- "For most mild infections, long Covid symptoms clear after a year, large study finds", Elizabeth Cooney, STAT, 1/12/23
    
    
14. "Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection", Stephanie A. Richard, Simon D. Pollett, Anthony C. Fries, et al, JAMA Network Open, 1/18/23
    -- "Lack of vaccination, severe illness tied to higher risk of long COVID", Mary Van Beusekom, CIDRAP, 1/19/23
    ... Note: The chart's cverage of this report has not been completed yet 
    
    
15. "The Epidemiology of Long COVID in US Adults", McKaylee M Robertson et al, Clinical Infectious Diseases, 12/21/22
    -- "Estimate says 19 million US adults have long COVID", Mary Van Beusekom, CIDRAP, 12/21/22
    ... Note: This report not yet included in the chart
    
    
16. "Association of COVID-19 Vaccination With Risk for Incident Diabetes After COVID-19 Infection", Alan C. Kwan, MD, MSc1; Joseph E. Ebinger, MD1; Patrick Botting, MSPH1; et al, JAMA Network Open, 2/14/23
    -- "Verified: COVID-19 Infection Increases Diabetes Risk", Cara Martinez, Cedars Sinai, 2/14/23
    -- "New study suggest people previously infected with COVID-19 could have increased risk for diabetes", Staff, CBS Los Angeles, 2/14/23
    ... Note: This report not yet included in the chart
    
    
17. "Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program",  Dhruv Khullar MD, MPP et al., Journal of General Internal Medicine, 2/16/23
    -- "NIH RECOVER research identifies potential long COVID disparities", NIH, 2/16/23
    ... Note: This report not yet included in the chart
    
    
18. "Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies", Peter A. Hall et al., Brain, Behavior, & Immunity - Health, 3/1/23
    -- "Long COVID linked to lower brain oxygen levels, cognitive problems and psychiatric symptoms", Waterloo News, 3/1/23
    ... Note: This report not yet included in the chart
    
    
19. "One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database", Andrea DeVries, Sonali Shambhu, Sue Sloop, et al, JAMA Health Forum, 3/3/23
    -- "Long Covid is associated with significantly increased risk of death, heart and lung problems, study finds", Janelle Chavez, CNN, 3/3/23
    ... Note: This report not yet included in the chart
    
    
20. "Long-term gastrointestinal outcomes of COVID-19, Evan Xu, Yan Xie & Ziyad Al-Aly ,Nature Communications, 3/7/23
    -- "Long Covid Patients More Likely to Have Gastrointestinal Problems, Study Finds", Long Covid Patients More Likely to Have Gastrointestinal Problems, Study Finds", Pam Belluck, NY Times, 3/7/23
    ... Note: This report not yet included in the chart
    
    
21. "Risk Factors Associated With Post−COVID-19 Condition", Vasiliki Tsampasian, Hussein Elghazaly,Rahul Chattopadhyay, et al, JAMA Network, 3/23/23
    -- "Who Is Most at Risk for Long Covid?", Pam Belluck, NY Times, 3/23/23
    ... Note: This report not yet included in the chart

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B.  Columns in the chart

The columns contain information about the symptoms, risk factors, preventions, treatments, and outcomes of long COVID.

• Column A -- The country, lead author, and name of. the journal in which the study was published. The name of the journal is hyperlinked to a free copy of the study on the Web
• Column B -- An abbreviated version of the full title of the study. See Section A (above) fo full title.
• Column C -- Publication date
• Column D -- Design: no experiments; all of the studies in this edition of the chart were observations, some from surveys, others from medical records. Some studies had matched control groups
• Column E -- Number of. cases in the study group and control group(s)
• Column F -- Symptoms = known diseases (e.g. diabetes, cardiovascular) or clusters of symptoms (fatigue, respiratory, cognitive) 
• Column G -- Risk factors that enhanced the likelihood of Long COVID, e.g., age, comorbidity, gender, and the severity of COVID infection
• Column H -- Preventions = vaccines and  Paxlovid
• Column I -- Treatments = none in this edition of the chart, except for known diseases, e.g., diabetes and cardiovascular
• Column J -- Outcomes are the principal findings, i.e., in this edition of the chart = who experienced long COVID, how severely, for how long?
  
  
• Readers can scroll this large chart from top to bottom and from left to right to view all of its rows and columns.

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CHART

 

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Comments about the chart    

The chart focuses on similarities between the risk factors, preventions, and treatments for COVID vs. the risk factors, preventions, and treatments for long COVID. This bias may cause it to underestimate important differences between these two diseases. 

• Overall outcomes 
  Three studies on the chart provide substantially different estimates of the percent of COVID survivors who contracted long COVID
  
  -- The CDC estimates (row 4) that about  1 in 4 (25 percent) of 65+ year olds experienced long COVID, but only  1 in 5 (20 percent) of 18 to 64 year olds 
  
  -- The Global Burden group (row 7) estimated that only 6.2 percent of COVID survivors developed long COVID.
  
  -- The ECDC meta analysis estimated that 51 percent of COVID survivors not hospitalized or in ICUs developed long COVID community
  
  Why such large differences in their estimates?
  -- One reason is the different definitions used by these studies. The CDC says that long COVID begins "at least four weeks after infection"; whereas the WHO definition used by Global Burden says that long COVID usually begins "3 months from the onset of COVID-19 with symptoms". Symptoms that arise after four weeks may disappear before the third month has passed.
  
  -- The ECDC report cautions that its high estimate may be due to the fact that many of the studies it reviewed did not have control groups that provided estimates of the prevalence of the same symptoms among non-infected persons
  
  
• Prevention (Vaccines)
  Given the extensive efforts that so many people of all ages have made to become vaccinated and receive at least one booster, not just the oldest and most vulnerable, it would be great to learn that vaccines not only protect against severe illness and death, they also protect us from long COVID. The chart includes four studies that referenced vaccines
  
  -- The earliest study (before Omicron), "Long COVID after breakthrough" (row 5), analyzed a massive set of records from the U.S. Veterans Administration that "Vaccination against SARS-CoV-2 lowers the risk of long COVID after infection by only about 15% "
  
  -- "Outcomes among confirmed cases" (row 8), found that "Preinfection vaccination was associated with reduced risk of some persistent symptoms. This study involved extensive surveys of large cohorts of long COVID survivors matched against a cohort whose members had never been infected
  
  -- Finally the most optimistic study, "Reduced incidence of Long COVID" (row 6), noted that the "Referrals to long COVID clinic fell by 79% following roll-out of the vaccine" in the U.K. Did the vaccines really cause the reduction in the incidence of long COVID and thereby cause the reduction in referrals? Or did the reductions reflect the impact of unidentified confounding variables?
  
  
• Prevention (Paxlovid)
  According to the study in row 10, cases at high risk for severe illness or death from COVID (old age and/or comorbidities) who took Paxlovid shortly after infection were 26 percent less likely to develop long COVID within 90 days
  
  
• Risk factors -- Age, Health conditions, severity of infection, and reinfection
  Old age and compromised health conditions have accounted for well over 90 percent of all deaths from COVID and the vast majority of those who became severely ill from COVID. Were the survivors who had these risk factors at higher risk of long COVID? Conversely, were those who only experienced asymptomatic COVID at lower risk for long COVID?
  
  -- The studies in rows 3, 4, 6, 7, 10 cited age
  
  -- The studies in rows 3, 8, 10 cited health conditions
  
  -- The study in row 11 cited reinfection as a major risk factor, even among persons who had been vaccinated or boosted
  
  -- The study in row 13 showed that mild COVID usually leads to limited long COVID, i.e., long COVID symptoms clear up within a year's time. This finding is important because under Omicron, the vast majority of COVID infections have been mild or asymptomatic.
  
  -- The study in row 8 found no long COVID among survivors of COVID who only had asymptomatic infections. Given that the youngest age groups have the highest incidence of asymptomatic infections, this finding suggests (but does not prove) that the youngest age groups are at the lowest risk of long COVID.
  
  -- The studies in rows 3, 5, 8, 9, and 12 found that the severity of long COVID is positively correlated with the severity of COVID infections. In other words, the most severe long COVID is preceded by the most severe COVID; less severe long COVID is preceded by mild to moderate COVID; and asymptomatic COVID, the least severe COVID, is associated with no long COVID at all. 
  
  This is, perhaps the most important finding in that it provides a framework for understanding other risk factors, vaccinations, and treatments. Indeed, the most severe form of COVID is death. Those most likely to die from COVID have been the elderly and/or persons having health co-morbidities. One is therefore not surprised that those who were most severely ill, but did not die, were those who were most likely to experience the most disruptive long COVID
  
  Furthermore, vaccines and Paxlovid reduce the severity of COVID; so it is not surprising that persons who were vaccinated and/or were treated with Paxlovid experienced less severe long COVID. 
  
  
  

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Links to related notes on this blog:  

• "Long COVID" ... This frequently updated reference page provides essential information about long COVID, a/k/a "Post-COVID", plus links to authoritative discussions of its likely victims, prevention, and treatments.
  
  
• "COVID FAQs", This reference page presents four FAQs about COVID that everyone should have at their fingertips. Updated bi-monthly.