Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID)

Abstract:

Background: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections.

Methods: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the ‘exposed cohorts’ and ‘reference cohort’ was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC.

Results: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final ‘matched’ analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts.

Conclusions: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Source: Pazukhina E, Rumyantsev M, Baimukhambetova D, Bondarenko E, Markina N, El-Taravi Y, Petrova P, Ezhova A, Andreeva M, Iakovleva E, Bobkova P, Pikuza M, Trefilova A, Abdeeva E, Galiautdinova A, Filippova Y, Bairashevskaia A, Zolotarev A, Bulanov N, DunnGalvin A, Chernyavskaya A, Kondrikova E, Kolotilina A, Gadetskaya S, Ivanova YV, Turina I, Eremeeva A, Fedorova LA, Comberiati P, Peroni DG, Nekliudov N, Genuneit J, Reyes LF, Brackel CLH, Mazankova L, Miroshina A, Samitova E, Borzakova S, Carson G, Sigfrid L, Scott JT, McFarland S, Greenhawt M, Buonsenso D, Semple MG, Warner JO, Olliaro P, Osmanov IM, Korsunskiy AA, Munblit D; Sechenov StopCOVID Research Team. Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID). BMC Med. 2024 Feb 1;22(1):48. doi: 10.1186/s12916-023-03221-x. PMID: 38302974; PMCID: PMC10835884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835884/ (Full text)

Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis

Abstract:

Background: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as “long COVID” or “post-acute sequelae of SARS-CoV-2 infection” (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

Methods: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

Results: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

Conclusions: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

Source: Hoshijima H, Mihara T, Seki H, Hyuga S, Kuratani N, Shiga T. Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis. PLoS One. 2023 Nov 29;18(11):e0250909. doi: 10.1371/journal.pone.0250909. PMID: 38019841; PMCID: PMC10686440. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686440/ (Full text)

Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany

Abstract:

Introduction: Long-term health effects of COVID-19 have been investigated by several large cohort studies. As most of these studies have been conducted in adults, data on the incidence and persistence of post-COVID-19 condition (PCC) among children and adolescents are still limited.
Methods: Using routine healthcare data from statutory health insurance in Germany, children and adolescents with laboratory-confirmed COVID-19 in 2020 were matched to controls (neither documented nor clinically suspected COVID-19) and followed for incident health conditions until 2021-09-30. To study PCC in children we considered selected health outcomes including malaise/fatigue (R53), dyspnea (R06.0), and cognitive dysfunction (F06.7, U51, R41), developmental delay (F80-89), adjustment disorder (F43), chronic fatigue syndrome (CFS; G93.3), and altered smell/anosmia (R43). The incidence of PCC was determined based on the lack of related diagnoses in the 12 months preceding the index quarter. For each outcome incidence rate ratios (IRR) were estimated using Poisson regression.
Results: At 3-month-follow-up, about 40% more individuals with COVID-19 suffered from at least one of the specified health conditions compared to controls. IRR were highest for smell/anosmia and CFS. IRR were generally higher among adolescents (≥12 years) than among younger children. Only a minority of PCC diagnoses persisted for 12 months within the COVID cohort. Diagnoses were more frequently persistent in the younger age group after one year.
Conclusions: Despite that long-term consequences of COVID-19 are less common and usually less severe in children, a considerable share of those diagnosed with PCC still suffered from specific symptoms 12 months after acute infection. Considering the high number of infected persons our findings suggest a relevant PCC related burden for health care even among children and adolescents.
Key messages:

• In routine healthcare data adolescents showed stronger associations between COVID-19 and post COVID-19 related ICD-10 diagnoses than children < 12 years of age.

• Serious ICD-10 diagnoses persisted for a longer time in younger children than adolescents.

Source: F Ehm, D Wende, F Loser, A Vivirito, S Menzer, M Batram, T Buschmann, G Sarganas, C Scheidt-Nave, J Schmitt, Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany, European Journal of Public Health, Volume 33, Issue Supplement_2, October 2023, ckad160.095, https://doi.org/10.1093/eurpub/ckad160.095 https://academic.oup.com/eurpub/article/33/Supplement_2/ckad160.095/7327923 (Full text available as PDF file)

Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022

Abstract:

Objective To characterise Long COVID in a highly vaccinated population infected by Omicron.

Design Follow-up survey of persons testing positive for SARS-CoV-2 in Western Australia, 16 July-3 August 2022.

Setting Community

Participants 22,744 persons with COVID-19 who had agreed to participate in research at the time of diagnosis were texted a survey link 90 days later; non-responders were telephoned. Post stratification weights were applied to responses from 11,697 (51.4%) participants, 94.0% of whom had received >= 3 vaccine doses.

Main outcome measures Prevalence of ‘Long COVID’ – defined as reporting new or ongoing COVID-19 illness-related symptoms or health issues 90 days post diagnosis; associated health care utilisation, reductions in work/study and risk factors were assessed using log-binomial regression.

Results 18.2% (n=2,130) of respondents met case definition for Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%); 38.2% consulted a GP and 1.6% reported hospitalisation in the month prior to the survey due to ongoing symptoms. Of 1,778 respondents with Long COVID who were working/studying before their COVID-19 diagnosis, 17.9% reported reducing/discontinuing work/study.

Conclusion 90 days post Omicron infection, almost 1 in 5 respondents reported Long COVID symptoms; 1 in 15 of all persons with COVID-19 sought healthcare for associated health concerns >=2 months after the acute illness.

The known The prevalence of Long COVID varies widely across studies conducted in diverse settings globally (range: 9%-81%).

The new In a highly vaccinated population (94% with >=3 vaccine doses), almost 20% of persons infected with the SARS-CoV-2 Omicron variant reported symptoms consistent with Long COVID 90 days post diagnosis. Long COVID was associated with sustained negative impacts on work/study and a substantial utilisation of GP services 2-3 months after the acute illness; however, ED presentations and hospitalisations for Long COVID were rare.

The implications GP clinics play a significant role in managing the burden of Long COVID in Australia.

Source: Mulu Woldegiorgis, Gemma Cadby, Sera Ngeh, Rosemary Korda, Paul Armstrong, Jelena Maticevic, Paul Knight, Andrew Jardine, Lauren Bloomfield, Paul Effler. Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022.

Long COVID prevalence and impact on quality of life 2 years after acute COVID-19

Abstract:

There has been an increasing interest in the long-term impact of long COVID. However, only a few studies have investigated the clinical manifestations of long COVID after 24 months of acute infection. In this study, prospective online surveys were conducted in adults previously diagnosed with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13, 2020, at 6, 12, and 24 months after COVID-19.

We investigated self-reported symptoms and the EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys. After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis. Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%), insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the incidence of long COVID at 24 months in terms of the number of vaccinations received.

Although the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants. Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time, and COVID-19 vaccination or the number of vaccinations received may not significantly affect the incidence of long COVID.

Source: Kim Y, Bae S, Chang HH, Kim SW. Long COVID prevalence and impact on quality of life 2 years after acute COVID-19. Sci Rep. 2023 Jul 11;13(1):11207. doi: 10.1038/s41598-023-36995-4. PMID: 37433819. https://www.nature.com/articles/s41598-023-36995-4 (Full text)

Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative

Abstract:

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively.

With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients.

We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.

Source: Zang C, Zhang Y, Xu J, Bian J, Morozyuk D, Schenck EJ, Khullar D, Nordvig AS, Shenkman EA, Rothman RL, Block JP, Lyman K, Weiner MG, Carton TW, Wang F, Kaushal R. Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative. Nat Commun. 2023 Apr 7;14(1):1948. doi: 10.1038/s41467-023-37653-z. PMID: 37029117; PMCID: PMC10080528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080528/ (Full text)

A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination

Abstract:

Current studies about the long-term effects of COVID-19 show a wide range of symptoms. This prospective cohort study aimed to find the incidence of long-COVID symptoms and the associated risk factors.

We followed 669 confirmed COVID-19 patients. Sociodemographic and clinical data were extracted from medical records and collected via semi-structured telephone interviews on days 10, 30, 60, and 90. The incidence of long-COVID symptoms was 41.6% (95% CI 37.8-45.4%). Females [aOR = 1.5 (95% CI 1.1-2.3)], the elderly [aOR = 4.9 (95% CI 2.0-11.3)], and those who required hospitalization [aOR = 5.0 (95% CI 1.3-3.7)] were at a higher risk of developing long-COVID. Patients with dyspnea at day 10 [aOR: 2.4 (95% CI 1.6-3.7] and fatigue at day 60 [aOR: 3.1 (95% CI 1.5-6.3] were also at risk. While non-vaccinated patients were almost seven times more likely to report long-COVID symptoms than vaccinated patients [aOR: 6.9 (95% CI 4.2-11.3)].

In conclusion, long-COVID was common among COVID-19 patients, with higher rates among females, older age groups, hospitalized patients, and those with dyspnea and fatigue, while vaccination provided protection. Interventions should educate health professionals, raise general public awareness about the risks and consequences of Long COVID, and the value of vaccination.

Source: Abu Hamdh B, Nazzal Z. A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination. Sci Rep. 2023 Mar 25;13(1):4896. doi: 10.1038/s41598-023-30583-2. PMID: 36966161; PMCID: PMC10039348. https://www.nature.com/articles/s41598-023-30583-2 (Full text)

Long Covid: clues about causes

Abstract:(Full text

Many patients report persistent symptoms after resolution of acute COVID-19, regardless of SARS-CoV-2 variant and even if the initial illness is mild [1, 2]. A multitude of symptoms have been described under the umbrella term ‘Long COVID’, otherwise known as ‘post-COVID syndrome’ or ‘post-acute sequelae of SARS-CoV-2 (PASC)’; for simplicity we will use the term Long COVID.

Symptoms are diverse but include breathlessness, fatigue and brain fog, reported to affect up to 69% of cases [3]. Long COVID can be debilitating, 45.2% of patients requiring a reduced work schedule [4]. The WHO estimates that 17 million people in Europe have experienced Long COVID during the first two years of the pandemic [5]. SARS-CoV-2 variants continue to circulate and the risk of post-acute complications remains; a recent study of 56 003 UK patients found that even after Omicron infection, 4.5% suffered persistent symptoms [6].

It is therefore likely that Long COVID will provide a substantial medical and economic burden for the foreseeable future. There is an urgent need to understand mechanisms of disease and develop effective treatments based on this understanding.

Source: Liew F, Efstathiou C, Openshaw PJ. Long Covid: clues about causes. Eur Respir J. 2023 Mar 23:2300409. doi: 10.1183/13993003.00409-2023. Epub ahead of print. PMID: 36958743; PMCID: PMC10040855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040855/ (Full text)

Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study

Abstract:

Objective: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition.

Study design: This was a cross-sectional questionnaire-based survey.

Methods: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses.

Results: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (β = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (β = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (β = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (β = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (β = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (β = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (β = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (β = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (β = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (β = -0.51, 95% CI = -0.94 to -0.09).

Conclusions: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

Source: Morioka S, Tsuzuki S, Maruki T, Terada M, Miyazato Y, Kutsuna S, Saito S, Shimanishi Y, Takahashi K, Sanada M, Ashida S, Akashi M, Kuge C, Osanai Y, Tanaka K, Suzuki M, Hayakawa K, Ohmagari N. Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study. Public Health. 2023 Feb 13;216:39-44. doi: 10.1016/j.puhe.2023.01.008. Epub ahead of print. PMID: 36791649. https://www.sciencedirect.com/science/article/pii/S0033350623000173?via%3Dihub (Full text)

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients

Abstract:

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies.

A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months.

The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Source: Di Gennaro F, Belati A, Tulone O, Diella L, Fiore Bavaro D, Bonica R, Genna V, Smith L, Trott M, Bruyere O, Mirarchi L, Cusumano C, Dominguez LJ, Saracino A, Veronese N, Barbagallo M. Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients. Intern Emerg Med. 2022 Nov 30:1–9. doi: 10.1007/s11739-022-03164-w. Epub ahead of print. PMID: 36449260; PMCID: PMC9709360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709360/ (Full text)