Long COVID-19
Long COVID is a form of COVID-19 involving a wide range of health conditions that can last for months or years. This form of COVID creates unique challenges in treatment options for patients as their symptoms persist beyond the acute COVID-19 infection. Here are some important resources to understand and combat long COVID.
For those members in research who might be interested, secure data from more than 14,000 adults who participate in National Institutes of Health observational research on long COVID are now available to authorized researchers through BioData Catalyst (BDC). BDC is a cloud-based ecosystem developed by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, to accelerate research on heart, lung, blood, and sleep disorders. The research on long COVID — broadly defined as signs, symptoms, or conditions that persist or develop for at least four weeks after an infection from the virus that causes COVID-19 is provided through the NIH Researching COVID to Enhance Recovery (NIH RECOVER) Initiative. Authorized researchers can now request access to a subset of data from adults in the observational RECOVER cohort. These data include information from more than 92,000 study visits collected between Oct. 29, 2021-Sept. 15, 2023 at 79 locations throughout the United States. New RECOVER data, including data from other studies, will be added to BDC at regular intervals. NIH RECOVER makes long COVID data easier to access | National Institutes of Health (NIH) - April 25, 2024
This study examined plasma proteins in 466 patients with at least one Long COVID symptom compared to 233 patients who symptoms had completely resolved and found that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials. Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease | Nature Immunology – April 8, 2024
This small study compared patients with Post COVID Condition (PCC) with matched controls and varying intensity levels of exercise and found that there were no profound symptom exacerbation among those with PCC but they did have more muscle pain after high-intensity interval training and more concentration problems after moderate intensity continuous training. Those with PCC also had lower aerobic capacity and less muscle strength. The authors concluded that cautious exercise training should be recommended for PCC patients to prevent further deconditioning. Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition: A Randomized Crossover Clinical Trial | Physical Medicine and Rehabilitation | JAMA Network Open | JAMA Network – April 4, 2024
A large retrospective cohort study showed that SARS-CoV-2 vaccination was 35.4% effective against probable Long COVID and 4.7% against diagnosed Long COVID. Vaccination was more effective in adolescents (50.3%) compared to 5-11 year olds (23.8%). Vaccine Effectiveness Against Long COVID in Children | Pediatrics | American Academy of Pediatrics (aap.org) - March 8, 2024
This study from England involved 112,964 adults who completed an online assessment of cognitive function. Those whose symptoms from COVID-19 had resolved by 12 weeks had small deficits in global cognition compared to the no-COVID group. Larger deficits were seen in participants with unresolved persistent symptoms (lasting greater than 12 weeks). The degree of deficit was related to the circulating variant at the time of infection. Memory, reasoning and executive function were associated with the largest deficits. Cognition and Memory after Covid-19 in a Large Community Sample | NEJM – February 29, 2024
This longitudinal population-based cohort study involving 112,311 individuals with a history of COVID-19 compared to two control groups found a higher risk for respiratory disease in the COVID-19 group compared to controls for asthma, COPD, bronchiectasis, interstitial lung disease, pulmonary vascular disease and lung cancer. The hazard ratio for asthma was 1.49 (95% CI, 1.28-1.74) and for COPD 1.59 (95% CI, 1.41-1.81). The risk increased with the severity of the infection, and reinfection. Long-term risks of respiratory diseases in patients infected with SARS-CoV-2: a longitudinal, population-based cohort study - eClinicalMedicine (thelancet.com) - February 17, 2024
The CDC analyzed data from noninstitutionalized U.S. adults aged ≥18 years participating in the 2022 Behavioral Risk Factor Surveillance System (BRFSS), a population-based cross-sectional survey (4). Respondents were sampled using random digit dialing of both landline and cellular telephones. Individuals from all 50 states and US Territories were interviewed. The overall prevalence was 6.4% and was noted to vary from 1.9% in the US Virgin Islands to 10.6% in West Virginia. Prevalence tended to be lower in New England and the Pacific and higher in the South, Midwest and West. Notes from the Field: Long COVID Prevalence Among Adults — United States, 2022 | MMWR (cdc.gov) – February 15, 2024
A survey study of 14,767 individuals with post-COVID condition (PCC) found that 57% reported experiencing cognitive symptoms daily, compared to 27% who did not develop PCC. Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning | Infectious Diseases | JAMA Network Open | JAMA Network - February 14, 2024
This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes. Postacute Sequelae of SARS-CoV-2 in Children | Pediatrics | American Academy of Pediatrics (aap.org) – February 7, 2024
In this study, 270 patients diagnosed with Post COVID Condition (PCC) from two different clinics in the UK and Germany were compared to two control groups: individuals who had contracted COVID-19 but did not develop PCC and uninfected individuals. Using short web-based cognitive tasks the authors found pronounced cognitive slowing in 53.5% of the patients with PCC compared to the control groups. Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study - eClinicalMedicine (thelancet.com) - January 24, 2024
This study in a small number of patients with symptoms consistent with Long COVID suggests evidence of persistent complement dysregulation and thromboinflammation. This might suggest clinical trials of complement modulation for treatment. Persistent complement dysregulation with signs of thromboinflammation in active Long COVID | Science - January 19, 2024
This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Keep in mind that Long COVID is declining among infected children, but this study compared vaccinated to unvaccinated. Vaccine Effectiveness Against Long COVID in Children | Pediatrics | American Academy of Pediatrics (aap.org) - January 16 2024
This study used ‘omic” assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. 25% had been hospitalized for COVID-19. 27 patients had clear-cut Long COVID. These individuals exhibited evidence of systemic inflammation and immune dysregulation, manifested by global differences in T cell subset distribution as well as be sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. The analysis suggested improper cross-talk between the cellular and humoral adaptive immunity in Long COVID. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2 | Nature Immunology - January 11, 2024
SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases and also targeted plaque macrophages. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels | Nature Cardiovascular Research - September 28, 2023
Immune profiling and biological features identified through machine learning revealed marked differences in circulating myeloid and lymphoid populations, exaggerated humoral responses against SAR-CoV-2 as well as other viruses. Distinguishing features of Long COVID identified through immune profiling | Nature - September 25, 2023
Multicenter MRI study in the UK found multiorgan abnormalities were found in 61% of adults hospitalized with COVID-19 compared to 27% of controls at a median of 5 months after discharge. Lung, brain and kidney were the most frequent involved organs. Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study - The Lancet Respiratory Medicine - September 22, 2023
Review of the immunology of Long COVID. The immunology of long COVID | Nature Reviews Immunology - September 18, 2023
This prospective study from Canada included 1026 8-13 year-old children who provided reports of symptoms every two weeks during the study period between August 2020 and March 2021. The rate of long-COVID symptoms as defined by the WHO was 0.4% and noted that pre-existing symptoms prior to COVID-19 were factors in post COVID symptoms. The study period preceded the delta and omicron, and may not apply to delta, but omicron has been reported to be associated with less long-COVID. Post–COVID-19 Condition in Children | Infectious Diseases | JAMA Pediatrics | JAMA Network - September 18, 2023
Review of studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir. Mechanisms by which these reservoirs may contribute to Long-COVID pathology are delineated. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) | Nature Immunology - September 4, 2023
Data from the National Health Interview Survey on Long COVID in adults is presented in this NCHS Data brief: db480.pdf (cdc.gov) - September 2023
This study from the CDC discussed the long lasting significant activity limitations among adults after the Omicron surge. Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023 | MMWR (cdc.gov) - August 11, 2023
This multicenter study of adults with COVID-like illness showed that symptoms can persist, emerge, reemerge or resolve after a COVID-like illness and are not unique to COVID-19 or to post-COVID conditions. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults — United States, December 2020–March 2023 | MMWR (cdc.gov) - August 11, 2023
A systematic review of persistent clinical features following COVID-19 in pediatrics: A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population | Pediatrics | American Academy of Pediatrics (aap.org) (free access) - July 21 2023
CDC archived webinar: Evaluating and Supporting Patients with Long COVID in Returning to Work: Webinar Thursday, June 15, 2023 - Evaluating and Supporting Patients with Long COVID in Returning to Work (cdc.gov)
In this study of 1106 adults who were not vaccinated before infection compared to 628 who were not infected, up to 18% had post-COIVD 19 condition up to two years after infection, with little change from 1-2 years. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study | The BMJ - May 31, 2023
In this analysis of data from 9764 participants in the RECOVER adult cohort, a prospective longitudinal cohort study, 37 symptoms across multiple pathophysiological domains were identified as present more often in SARS-CoV-2–infected participants at 6 months or more after infection compared with uninfected participants. A preliminary rule for identifying PASC was derived based on a composite symptom score. In addition, this study noted that 30% of those with symptoms at 6 months were symptom-free at 9 months. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection | Neurology | JAMA | JAMA Network - May 25, 2023
Analysis of data on almost 10,000 patients from the RECOVER adult prospective cohort trial revealed key symptoms that could be used to identify patients with long COVID. They were, in decreasing order of frequency: post-exertional malaise, fatigue, brain fog, dizziness, GI symptoms, palpitations, loss of libido, loss of smell or taste, thirst, hair loss, chronic cough, chest pain, and abnormal movements. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection | Infectious Diseases | JAMA | JAMA Network
VA Guidebook on Long COVID
The Department of Veterans Affairs published a new guidebook on caring for veterans with long COVID. Titled the Whole Health System Approach to Long COVID, the guidebook provides information about signs, symptoms and treatments for the illness. The guidebook also includes metrics, such as surveys, to assess autonomic symptoms. This is an excellent resource when confronted with a patient with potential long COVID. (11/7/22)
Additional Resources
Long COVID or Post-COVID Conditions | CDC (for patients) and Post-COVID Conditions: Information for Healthcare Providers (cdc.gov) for providers and the NIH website Long COVID | NIH COVID-19 Research