Tag: covid vaccine

Divergent Adaptive Immune Responses Define Two Types Of Long Covid

The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination.

Long COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29).

The spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups.

Multiplexed antibody analyses to 30 different viral antigens showed that LC-patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC-patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC-group.

These findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID.

Source: Jérôme Kervevan, Isabelle Staropoli, Dorsaf Slama, Raphaël Jeger-Madiot, Françoise Donnadieu, Delphine Planas, Marie-Pierre Pietri, Wiem Loghmari-Bouchneb, Motolete A. Tanah, Rémy Robinot, Faroudy Boufassa, Michael White, Dominique SALMON and Lisa A. Chakrabarti. Front. Immunol. Sec. Viral Immunology. Volume 14 – 2023 | doi: 10.3389/fimmu.2023.1221961 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1221961/abstract

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up

Abstract:

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry.

In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization.

The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Source: Babicki M, Kapusta J, Pieniawska-Śmiech K, Kałuzińska-Kołat Ż, Kołat D, Mastalerz-Migas A, Jankowski P, Chudzik M. Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up. Viruses. 2023 Jun 13;15(6):1370. doi: 10.3390/v15061370. PMID: 37376668; PMCID: PMC10304551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304551/ (Full text)

Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID

Abstract:

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown.

Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers.

In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.

Source: Visvabharathy L, Zhu C, Orban ZS, Yarnoff K, Palacio N, Jimenez M, Lim PH, Penaloza-MacMaster P, Koralnik IJ. Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID. medRxiv [Preprint]. 2023 Apr 12:2023.04.07.23288243. doi: 10.1101/2023.04.07.23288243. PMID: 37090595; PMCID: PMC10120795. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120795/ (Full text)

Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study

Abstract:

Objective: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection.

Design: Population based, longitudinal cohort.

Setting: General population of canton of Zurich, Switzerland.

Participants: 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection.

Main outcome measures: Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection.

Results: 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)).

Conclusions: Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials.

Registrations: ISRCTN18181860

Source: Ballouz T, Menges D, Anagnostopoulos A, Domenghino A, Aschmann HE, Frei A, Fehr JS, Puhan MA. Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. BMJ. 2023 May 31;381:e074425. doi: 10.1136/bmj-2022-074425. PMID: 37257891. https://www.bmj.com/content/381/bmj-2022-074425 (Full text)

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

Key Points:

Question  What symptoms are differentially present in SARS-CoV-2–infected individuals 6 months or more after infection compared with uninfected individuals, and what symptom-based criteria can be used to identify postacute sequelae of SARS-CoV-2 infection (PASC) cases?

Findings  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.

Meaning  A framework for identifying PASC cases based on symptoms is a first step to defining PASC as a new condition. These findings require iterative refinement that further incorporates clinical features to arrive at actionable definitions of PASC.

Abstract:

Importance  SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

Objective  To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

Design, Setting, and Participants  Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.

Exposure  SARS-CoV-2 infection.

Main Outcomes and Measures  PASC and 44 participant-reported symptoms (with severity thresholds).

Results  A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.

Conclusions and Relevance  A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Source: Thaweethai T, Jolley SE, Karlson EW, et al. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. Published online May 25, 2023. doi:10.1001/jama.2023.8823 https://jamanetwork.com/journals/jama/fullarticle/2805540 (Full text)

How Does Long-COVID Impact Prognosis and the Long-Term Sequelae?

Abstract:

Context: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course.
Objective: To conduct a narrative review synthesizing current clinical evidence of abnormalities of signs, symptoms, and complementary studies in COVID-19 patients who presented a prolonged and complicated course.
Methods: A review of the literature focused on the involvement of the main organic functions mentioned, based almost exclusively on the systematic search of publications written in English available on PubMed/MEDLINE.
Results: Long-term respiratory, cardiac, digestive, and neurological/psychiatric dysfunction are present in a significant number of patients. Lung involvement is the most common; cardiovascular involvement may happen with or without symptoms or clinical abnormalities; gastrointestinal compromise includes the loss of appetite, nausea, gastroesophageal reflux, diarrhea, etc.; and neurological/psychiatric compromise can produce a wide variety of signs and symptoms, either organic or functional. Vaccination is not associated with the emergence of long-COVID, but it may happen in vaccinated people.
Conclusions: The severity of illness increases the risk of long-COVID. Pulmonary sequelae, cardiomyopathy, the detection of ribonucleic acid in the gastrointestinal tract, and headaches and cognitive impairment may become refractory in severely ill COVID-19 patients.
Source: Baroni C, Potito J, Perticone ME, Orausclio P, Luna CM. How Does Long-COVID Impact Prognosis and the Long-Term Sequelae? Viruses. 2023; 15(5):1173. https://doi.org/10.3390/v15051173 https://www.mdpi.com/1999-4915/15/5/1173 (Full text)

COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

Abstract:

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and over 13 billion COVID-19 vaccine doses have been administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to an acute disease, i.e. COVID-19, but also to a post-acute COVID-19 syndrome (PACS, “long COVID”). Currently, the side effects of COVID-19 vaccines are increasingly being noted and studied.

Here, we summarise the currently available indications and discuss our conclusions that (i) these side effects have specific similarities and differences to acute COVID-19 and PACS, that (ii) a new term should be used to refer to these side effects (post-COVID-19 vaccination syndrome, PCVS, colloquially “post-COVIDvac-syndrome”), and that (iii) there is a need to distinguish between acute COVID-19 vaccination syndrome (ACVS) and post-acute COVID-19 vaccination syndrome (PACVS) – in analogy to acute COVID-19 and PACS (“long COVID”). Moreover, we address mixed forms of disease caused by natural SARS-CoV-2 infection and COVID-19 vaccination.

We explain why it is important for medical diagnosis, care and research to use the new terms (PCVS, ACVS and PACVS) in order to avoid confusion and misinterpretation of the underlying causes of disease and to enable optimal medical therapy. We do not recommend to use the term “Post-Vac-Syndrome” as it is imprecise. The article also serves to address the current problem of “medical gaslighting” in relation to PACS and PCVS by raising awareness among the medical professionals and supplying appropriate terminology for disease.

Source: Scholkmann F, May CA. COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences. Pathol Res Pract. 2023 May 3;246:154497. doi: 10.1016/j.prp.2023.154497. Epub ahead of print. PMID: 37192595; PMCID: PMC10154064. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154064/ (Full text)

Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study

Abstract:

Background: Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol.

Methods: We performed a prospective “disease-based” cohort study between 01/02/2020 to 31/10/2022 including children aged 0-18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher’s exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan-Meier method.

Findings: 1243 children were included, median age: 7.5 (4-10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18-1.28), comorbidities (OR 1.68; 95% CI 1.14-2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91-12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC.

Interpretation: In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed.

Funding: This study has been funded by Pfizer non-competitive grant, granted to DB (# 65925795).

Source: Morello R, Mariani F, Mastrantoni L, De Rose C, Zampino G, Munblit D, Sigfrid L, Valentini P, Buonsenso D. Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study. EClinicalMedicine. 2023 May;59:101961. doi: 10.1016/j.eclinm.2023.101961. Epub 2023 Apr 14. PMID: 37073325; PMCID: PMC10101848. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00138-4/fulltext (Full text)

Vaccine perceptions among Black adults with long COVID

Abstract:

Objectives: Low uptake of COVID vaccines within Black communities is a concern given the stark racial inequities associated with the pandemic. Prior research details COVID vaccine perceptions within the general population and Black communities specifically. However, Black individuals with long COVID may be more or less receptive to future COVID vaccination than their peers without long COVID. The impact of COVID vaccination on long COVID symptoms is still controversial, since some studies suggest that vaccination can improve long COVID symptoms, whereas other studies report no significant change in symptoms or a worsening of symptoms. In this study, we aimed to characterize the factors influencing perceptions of COVID vaccines among Black adults with long COVID to inform future vaccine-related policies and interventions.

Design: We conducted 15 semi-structured, race-concordant interviews over Zoom with adults who reported physical or mental health symptoms that lingered for a month or more after acute COVID infection. We transcribed and anonymized the interviews and implemented inductive, thematic analysis to identify factors influencing COVID vaccine perceptions and the vaccine decision-making process.

Results: We identified five themes that influenced vaccine perceptions: (1) Vaccine safety and efficacy; (2) Social implications of vaccination status; (3) Navigating and interpreting vaccine-related information; (4) Possibility of abuse and exploitation by the government and scientific community; and (5) Long COVID status. Safety concerns were amplified by long COVID status and mistrust in social systems due to mistreatment of the Black community.

Conclusions: Among the factors influencing COVID vaccine perceptions, participants reported a desire to avoid reinfection and a negative immune response. As COVID reinfection and long COVID become more common, achieving adequate uptake of COVID vaccines and boosters may require approaches that are tailored in partnership with the long COVID patient community.

Source: Dell’Imperio SG, Aboul-Hassan D, Batchelor R, Chambers-Peeple K, Clauw DJ, DeJonckheere M, Bergmans RS. Vaccine perceptions among Black adults with long COVID. Ethn Health. 2023 Apr 2:1-21. doi: 10.1080/13557858.2023.2191914. Epub ahead of print. PMID: 37005013. https://pubmed.ncbi.nlm.nih.gov/37005013/

Coronavirus (COVID-19) Pandemic – A Comprehensive Review of Demographics, Comorbidities, Vaccines, Therapeutic Development, Blood Type, and Long Covid

Abstract:

The study summarizes the pandemic COVID-19’s impact on symptoms, demographics, comorbidities, and vaccine and therapeutic development and demonstrates an association with cases and mortality for the past two years. There has been rapid scientific advancement over the past two years 2020-2022 in developing vaccines and therapeutics for combating the disease. We chose three highly affected countries US, India, and China, to address the impact of demographics and comorbidities on COVID-19 using US Center for Disease Control and Prevention (CDC) data.

Based on the analysis of this data, we see that the infection rate is higher in females, while the percentage of death is higher in males than females (p < 0.0001), and the number of female cases among females has increased by 1.7% while the number of deaths among females has decreased by ~1%, within the last two years. The trend of getting affected byCOVID-19 is similar during 2020-2022, i.e., Whites followed by Hispanics and Black people.

After a thorough review of many manuscripts, we concluded that diseases like cardiovascular disease (CVD), diabetes, hypertension, chronic pulmonary obstructive disease (COPD), and acute respiratory distress syndrome (ARDS) were the typical comorbidities leading to severe COVID-19 conditions. In addition, variants of COVID-19, current vaccine and therapeutic development efforts, and relation of COVID-19 with blood type are discussed.

Finally, to conclude that for designing vaccine trials, following FDA’s guidance emphasizing stratification factors based on demographics and comorbidities should be considered while allocating treatment to patients.

Source: Bhattacharyya, Arinjita & Seth, Anand & Rai, Shesh. (2023). Coronavirus (COVID-19) Pandemic -A Comprehensive Review of Demographics, Comorbidities, Vaccines, Therapeutic Development, Blood Type, and Long Covid. 10.36959/856/540.  https://www.researchgate.net/profile/Arinjita_Bhattacharyya/publication/369579104_Coronavirus_COVID-19_Pandemic_-A_Comprehensive_Review_of_Demographics_Comorbidities_Vaccines_Therapeutic_Development_Blood_Type_and_Long_Covid/links/6423001ba1b72772e4318d7d/Coronavirus-COVID-19-Pandemic-A-Comprehensive-Review-of-Demographics-Comorbidities-Vaccines-Therapeutic-Development-Blood-Type-and-Long-Covid.pdf (Full text PDF file)