Post by Nadica (She/Her) on Jul 23, 2024 1:52:02 GMT
Viral Variants, Vaccinations, and Long Covid — New Insights - Published July 17, 2024
New infections with SARS-CoV-2 continue 4 years after the pandemic began, despite advances in vaccines, antiviral medications, and preventive measures.1 Beyond the serious complications of Covid-19, the postviral syndrome known as postacute sequelae of SARS-CoV-2 infection (PASC), or “long Covid,” remains a major public health problem.2 The prevalence of long Covid is estimated to be 6.9% among noninstitutionalized persons in the United States who were previously infected with SARS-CoV-2.3 But defining the true incidence, underlying pathophysiology, full manifestations, and prognosis of long Covid continues to challenge patients who have been affected by PASC, as well as providers and investigators. In part, this situation is due to the heterogeneous presentation, wide-ranging tissue involvement, and highly variable course of long Covid. The viral load during the acute phase of SARS-CoV-2 infection and the timing of viral clearance probably play some role in the pathophysiology of the disease, but much of the heterogeneity is almost certainly related to the host immune response and to the affected person’s health before infection.4,5 Several risk factors predispose patients to long Covid: the initial severity of disease, previous hospitalization, and coexisting conditions such as diabetes and cardiopulmonary disease.6 Still, predicting the risk of PASC remains tenuous, especially among persons infected during the omicron era.
An enduring lesson from studying the epidemiology of long Covid is that time itself is a major confounder in risk prediction. PASC is not just an array of symptoms but spans a continuum after SARS-CoV-2 infection. As such, a patient’s long-term clinical course not only depends on the initial response to the virus and the resetting of the immune system due to chronic inflammation but also relates to points in time. These multiple variables must be considered when trying to understand the clinical picture of long Covid, including the time in the hospital, the time of or between vaccinations, the length of time since the first infection or between reinfection, the timing of treatment, the point in time of exposure to a particular viral strain, and the timing of the appearance of symptoms. These many variables confound both risk estimates and prognostic indicators.6,7
Xie et al.8 now report in the Journal two critical “points in time” that define the risk of PASC — pandemic era and time of Covid-19 vaccine introduction. The investigators reviewed the electronic health records from the Department of Veterans Affairs of nearly half a million persons with SARS-CoV-2 infections in an effort to determine the factors that predicted PASC. They studied eight cohorts — five cohorts with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and three noninfected contemporaneous control cohorts of 4.7 million persons — to estimate the cumulative incidence of PASC at 1 year after infection. They examined several health outcomes defined on the basis of multiple data domains, including International Classification of Diseases, 10th Revision, diagnosis codes, laboratory values, and prescription medications. The authors then divided “points in time” into three eras in which specific SARS-CoV-2 variants were the dominant lineage — the pre-delta era, the delta era, and the omicron era. They also examined vaccination records — data from additional points in time. The investigators took pains to consider a number of covariates, including age, race, ethnic group, sex as reported by the participant, area deprivation index, smoking status, and use of long-term care services. Blood pressure and body-mass index were also included among the covariates.
Overall, the amassed data showed that the cumulative incidence of long Covid decreased over the course of the pandemic, from a high of 10.42 cases per 100 persons at 1 year after infection during the pre-delta era to a low of 3.50 cases per 100 persons at 1 year among vaccinated persons who had SARS-CoV-2 infection during the omicron era. Still, there was a residual risk of long Covid among vaccinated persons infected during the omicron era (the most recent era of the pandemic), a finding that implies that new cases of PASC will probably continue to occur. Using decomposition analyses, the authors reported that the decrease in the cumulative risk of PASC between the omicron era and the pre-delta and delta eras combined could be attributed to two major factors: effects related to pandemic era (28% of the decrease) and vaccines (72% of the decrease). An additional and important finding was that although the risk of most sequelae from acute Covid-19 decreased across the eras, the risk of metabolic and gastrointestinal disorders increased, particularly among unvaccinated persons.
What are the messages from this study? First, vaccinations can prevent many but not all cases of long Covid.8,9 Second, viral variants influence the risk of PASC. Third, the study suggests that new cases of PASC may continue unabated, owing to a potentially greater prevalence of metabolic dysfunction and its associated coexisting conditions among persons infected during the omicron era.10 Taken together, changes in the clinical presentation of long Covid are a function of “points in time” and must be considered in any future trial or study design, as well as in clinical assessments.
However, it should be noted that observational studies have limitations. This study provides a snapshot across only the first 2 years of the pandemic (March 2020 through January 2022) and focuses primarily on male U.S. veterans. Second, studies such as this can miss confounding variables and lead to the misclassification of SARS-CoV-2 infection status owing to the use of electronic health records. Notwithstanding these limitations, the data from this study provide investigators with insight into the epidemiology of a complex disorder and may help guide clinicians in understanding the perplexing clinical course of PASC.
New infections with SARS-CoV-2 continue 4 years after the pandemic began, despite advances in vaccines, antiviral medications, and preventive measures.1 Beyond the serious complications of Covid-19, the postviral syndrome known as postacute sequelae of SARS-CoV-2 infection (PASC), or “long Covid,” remains a major public health problem.2 The prevalence of long Covid is estimated to be 6.9% among noninstitutionalized persons in the United States who were previously infected with SARS-CoV-2.3 But defining the true incidence, underlying pathophysiology, full manifestations, and prognosis of long Covid continues to challenge patients who have been affected by PASC, as well as providers and investigators. In part, this situation is due to the heterogeneous presentation, wide-ranging tissue involvement, and highly variable course of long Covid. The viral load during the acute phase of SARS-CoV-2 infection and the timing of viral clearance probably play some role in the pathophysiology of the disease, but much of the heterogeneity is almost certainly related to the host immune response and to the affected person’s health before infection.4,5 Several risk factors predispose patients to long Covid: the initial severity of disease, previous hospitalization, and coexisting conditions such as diabetes and cardiopulmonary disease.6 Still, predicting the risk of PASC remains tenuous, especially among persons infected during the omicron era.
An enduring lesson from studying the epidemiology of long Covid is that time itself is a major confounder in risk prediction. PASC is not just an array of symptoms but spans a continuum after SARS-CoV-2 infection. As such, a patient’s long-term clinical course not only depends on the initial response to the virus and the resetting of the immune system due to chronic inflammation but also relates to points in time. These multiple variables must be considered when trying to understand the clinical picture of long Covid, including the time in the hospital, the time of or between vaccinations, the length of time since the first infection or between reinfection, the timing of treatment, the point in time of exposure to a particular viral strain, and the timing of the appearance of symptoms. These many variables confound both risk estimates and prognostic indicators.6,7
Xie et al.8 now report in the Journal two critical “points in time” that define the risk of PASC — pandemic era and time of Covid-19 vaccine introduction. The investigators reviewed the electronic health records from the Department of Veterans Affairs of nearly half a million persons with SARS-CoV-2 infections in an effort to determine the factors that predicted PASC. They studied eight cohorts — five cohorts with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and three noninfected contemporaneous control cohorts of 4.7 million persons — to estimate the cumulative incidence of PASC at 1 year after infection. They examined several health outcomes defined on the basis of multiple data domains, including International Classification of Diseases, 10th Revision, diagnosis codes, laboratory values, and prescription medications. The authors then divided “points in time” into three eras in which specific SARS-CoV-2 variants were the dominant lineage — the pre-delta era, the delta era, and the omicron era. They also examined vaccination records — data from additional points in time. The investigators took pains to consider a number of covariates, including age, race, ethnic group, sex as reported by the participant, area deprivation index, smoking status, and use of long-term care services. Blood pressure and body-mass index were also included among the covariates.
Overall, the amassed data showed that the cumulative incidence of long Covid decreased over the course of the pandemic, from a high of 10.42 cases per 100 persons at 1 year after infection during the pre-delta era to a low of 3.50 cases per 100 persons at 1 year among vaccinated persons who had SARS-CoV-2 infection during the omicron era. Still, there was a residual risk of long Covid among vaccinated persons infected during the omicron era (the most recent era of the pandemic), a finding that implies that new cases of PASC will probably continue to occur. Using decomposition analyses, the authors reported that the decrease in the cumulative risk of PASC between the omicron era and the pre-delta and delta eras combined could be attributed to two major factors: effects related to pandemic era (28% of the decrease) and vaccines (72% of the decrease). An additional and important finding was that although the risk of most sequelae from acute Covid-19 decreased across the eras, the risk of metabolic and gastrointestinal disorders increased, particularly among unvaccinated persons.
What are the messages from this study? First, vaccinations can prevent many but not all cases of long Covid.8,9 Second, viral variants influence the risk of PASC. Third, the study suggests that new cases of PASC may continue unabated, owing to a potentially greater prevalence of metabolic dysfunction and its associated coexisting conditions among persons infected during the omicron era.10 Taken together, changes in the clinical presentation of long Covid are a function of “points in time” and must be considered in any future trial or study design, as well as in clinical assessments.
However, it should be noted that observational studies have limitations. This study provides a snapshot across only the first 2 years of the pandemic (March 2020 through January 2022) and focuses primarily on male U.S. veterans. Second, studies such as this can miss confounding variables and lead to the misclassification of SARS-CoV-2 infection status owing to the use of electronic health records. Notwithstanding these limitations, the data from this study provide investigators with insight into the epidemiology of a complex disorder and may help guide clinicians in understanding the perplexing clinical course of PASC.