Acute and postacute sequelae associated with SARS-CoV-2 reinfection

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Abstract

First infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs’ national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection ( n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control ( n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection contributed additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at 6 months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

Abstract

A new analysis using US Department of Veterans Affairs databases showed that reinfection is associated with increased risk of all-cause mortality, hospitalization and a wide range of long COVID complications in individuals who have had SARS-CoV-2 compared to those with no reinfection.

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Post-acute COVID-19 syndrome

Ani Nalbandian, Kartik Sehgal, Aakriti Gupta … (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

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Persistent Symptoms in Patients After Acute COVID-19

Angelo Carfì, Roberto Bernabei, Francesco Landi (2020)

This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.

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Characterizing long COVID in an international cohort: 7 months of symptoms and their impact

Hannah Davis, Gina Assaf, Lisa McCorkell … (2021)

Background A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. Few systematic studies have investigated this population, particularly in outpatient settings. Hence, relatively little is known about symptom makeup and severity, expected clinical course, impact on daily functioning, and return to baseline health. Methods We conducted an online survey of people with suspected and confirmed COVID-19, distributed via COVID-19 support groups (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters) and social media (e.g. Twitter, Facebook). Data were collected from September 6, 2020 to November 25, 2020. We analyzed responses from 3762 participants with confirmed (diagnostic/antibody positive; 1020) or suspected (diagnostic/antibody negative or untested; 2742) COVID-19, from 56 countries, with illness lasting over 28 days and onset prior to June 2020. We estimated the prevalence of 203 symptoms in 10 organ systems and traced 66 symptoms over seven months. We measured the impact on life, work, and return to baseline health. Findings For the majority of respondents (>91%), the time to recovery exceeded 35 weeks. During their illness, participants experienced an average of 55.9+/- 25.5 (mean+/-STD) symptoms, across an average of 9.1 organ systems. The most frequent symptoms after month 6 were fatigue, post-exertional malaise, and cognitive dysfunction. Symptoms varied in their prevalence over time, and we identified three symptom clusters, each with a characteristic temporal profile. 85.9% of participants (95% CI, 84.8% to 87.0%) experienced relapses, primarily triggered by exercise, physical or mental activity, and stress. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 1700 respondents (45.2%) required a reduced work schedule compared to pre-illness, and an additional 839 (22.3%) were not working at the time of survey due to illness. Cognitive dysfunction or memory issues were common across all age groups (~88%). Except for loss of smell and taste, the prevalence and trajectory of all symptoms were similar between groups with confirmed and suspected COVID-19. Interpretation Patients with Long COVID report prolonged, multisystem involvement and significant disability. By seven months, many patients have not yet recovered (mainly from systemic and neurological/cognitive symptoms), have not returned to previous levels of work, and continue to experience significant symptom burden. Funding All authors contributed to this work in a voluntary capacity. The cost of survey hosting (on Qualtrics) and publication fee was covered by AA's research grant (Wellcome Trust/Gatsby Charity via Sainsbury Wellcome center, UCL).

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Author and article information

Contributors

Ziyad Al-Aly:

ORCID: http://orcid.org/0000-0002-2600-0434

zalaly@gmail.com

Journal

Journal ID (nlm-ta): Nat Med

Journal ID (iso-abbrev): Nat Med

Title: Nature Medicine

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date (Electronic): 10 November 2022

Publication date PMC-release: 10 November 2022

Publication date (Print): 2022

Volume: 28

Issue: 11

Pages: 2398-2405

Affiliations

[1 ]Clinical Epidemiology Center, Research and Development Service, Veteran Affairs Saint Louis Health Care System, St. Louis, MO USA

[2 ]Veterans Research and Education Foundation of St. Louis, St. Louis, MO USA

[3 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Medicine, , Washington University School of Medicine, ; St. Louis, MO USA

[4 ]Nephrology Section, Medicine Service, Veteran Affairs St. Louis Health Care System, St. Louis, MO USA

[5 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Institute for Public Health, , Washington University in St. Louis, ; St. Louis, MO USA

Author information

Yan Xie http://orcid.org/0000-0002-2457-9382

Ziyad Al-Aly http://orcid.org/0000-0002-2600-0434

Article

Publisher ID: 2051

DOI: 10.1038/s41591-022-02051-3

PMC ID: 9671810

PubMed ID: 36357676

SO-VID: 463b25a0-baa6-4234-8255-6e65d5c4c144

License:

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