Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study

Abstract:

Objectives: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status.

Design: Retrospective nationwide cohort study.

Setting: Electronic medical records from an Israeli nationwide healthcare organisation.

Population: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.

Main outcome measures: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.

Results: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.

Conclusions: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Source: Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, Kalkstein N, Akiva P, Ekka-Zohar A, Ben David SS, Lerner U, Bivas-Benita M, Greenfeld S. Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023 Jan 11;380:e072529. doi: 10.1136/bmj-2022-072529. PMID: 36631153; PMCID: PMC9832503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832503/ (Full text)

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective

Abstract:

Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID.
Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale.
Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1–3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0–4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08–3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2–47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1–3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4–0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2–0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%).
Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.
Source: Guzman-Esquivel J, Mendoza-Hernandez MA, Guzman-Solorzano HP, Sarmiento-Hernandez KA, Rodriguez-Sanchez IP, Martinez-Fierro ML, Paz-Michel BA, Murillo-Zamora E, Rojas-Larios F, Lugo-Trampe A, Plata-Florenzano JE, Delgado-Machuca M, Delgado-Enciso I. Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective. Healthcare. 2023; 11(2):197. https://doi.org/10.3390/healthcare11020197 https://www.mdpi.com/2227-9032/11/2/197 (Full text)

Characteristics and predictors of Long COVID among diagnosed cases of COVID-19

Abstract:

Background: Long COVID or long-term symptoms after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe acute COVID-19 cases. We did this study to estimate the incidence and identify the characteristics and predictors of Long COVID among our patients.

Methodology: We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks and six months of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.

Results: We have analyzed 487 and 371 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47) and 223 days (IQR:195,251), respectively. Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) and 9.4% (95% CI: 6.7%,12.9%) of participants at four weeks and six months of follow-up, respectively. Incidence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n = 72) at four weeks of follow-up. At six months, the incidence among mild/moderate (n = 319) was 7.2% (95% CI:4.6%,10.6%) as compared to 23.1% (95% CI:12.5%,36.8%) in severe/critical (n = 52). The most common Long COVID symptom was fatigue. Statistically significant predictors of Long COVID at four weeks of follow-up were-Pre-existing medical conditions (Adjusted Odds ratio (aOR) = 2.00, 95% CI: 1.16,3.44), having a higher number of symptoms during acute phase of COVID-19 disease (aOR = 11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR = 2.32, 95% CI: 1.17,4.58), the severity of illness (aOR = 5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR) = 3.89, 95% CI: 2.49,6.08).

Conclusion: A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.

Source: Arjun MC, Singh AK, Pal D, Das K, G A, Venkateshan M, Mishra B, Patro BK, Mohapatra PR, Subba SH. Characteristics and predictors of Long COVID among diagnosed cases of COVID-19. PLoS One. 2022 Dec 20;17(12):e0278825. doi: 10.1371/journal.pone.0278825. PMID: 36538532; PMCID: PMC9767341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767341/ (Full text)

Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort

Abstract:

Importance: Persistent symptoms after SARS-COV-2 infection, or long-COVID, may occur in anywhere from 10-55% of those who have had COVID-19, but the extent of impact on daily functioning and disability remains unquantified.

Objective: To characterize physical and mental disability associated with long-COVID.

Design: Cross-sectional analysis of baseline data from a cohort study.

Setting: Online US nationwide survey.

Participants: Adults 18 years of age and older who live in the US who either report a history of COVID-19 illness (n=8,874) or report never having had COVID-19 (n=633).

Main outcome and measures: Self-reported mobility disability (difficulty walking a quarter of a mile and/or up 10 stairs, instrumental activities of daily living [IADL] disability (difficulty doing light or heavy housework), and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI).

Results: Of 7,926 participants with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity. Sixty-five percent of long-COVID participants were classified as having at least one disability, compared to 6% of those with resolved-COVID (n=948) and 14% of those with no-COVID (n=633). Of long-COVID participants, about 1% and 5% were classified as critically physically disabled or mentally fatigued, respectively. Age, prior comorbidity, increased BMI, female gender, hospitalization for COVID-19, non-white race, and multi-race were all associated with significantly higher disability burden. Dizziness at the time of infection (33% non-hospitalized, 39% hospitalized) was associated with all five disability components in both hospitalized and non-hospitalized groups. Heavy limbs, dyspnea, and tremors were associated with four of the five components of disability in the non-hospitalized group, and heavy limbs was associated with four of the five components in the hospitalized group. Vaccination was protective against development of disability.

Conclusion and relevance: We observed a high burden of physical and mental disability associated with long-COVID which has serious implications for individual and societal health that may be partially mitigated by vaccination. Longitudinal characterization and evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.

Source: Lau B, Wentz E, Ni Z, Yenokyan K, Coggiano C, Mehta SH, Duggal P. Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort. medRxiv [Preprint]. 2022 Dec 7:2022.12.07.22283203. doi: 10.1101/2022.12.07.22283203. PMID: 36523402; PMCID: PMC9753791. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9753791/ (Full text)

Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions

Abstract:

COVID-19 caused by SARS-CoV-2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS-CoV-2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID.

We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs.

Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID-19.

Source: He ST, Wu K, Cheng Z, He M, Hu R, Fan N, Shen L, Li Q, Fan H, Tong Y. Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions. MedComm (2020). 2022 Dec 8;3(4):e196. doi: 10.1002/mco2.196. PMID: 36514781; PMCID: PMC9732402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732402/ (Full text)

Long COVID and older people

Abstract:

Long COVID is a poorly understood condition, with a wide spectrum of effects on multiple body systems and variable presentation in different individuals. Long COVID is of particular concern among older people (ie, aged 65 years or older), who are at greater risk than younger people of persisting symptoms associated with COVID-19. In addition, COVID-19 might trigger or exacerbate chronic conditions that occur commonly in older people, such as cardiovascular diseases, respiratory diseases, neurodegenerative conditions, and functional decline.

In addition, the disruptive effects of COVID-19 for older people should not be underestimated; lockdowns and other restrictions might have reduced the social interactions of older people, and they are also likely to have lost a spouse or loved one during the pandemic, which can contribute to mental and physical decline.

COVID-19 vaccination appears to reduce the effects of long COVID, and older people, especially those living in aged care facilities, should remain up-to-date with their COVID-19 vaccinations. Health-care staff should also consider long COVID in the differential diagnosis of relevant symptoms in older people, rather than assume increasing frailty, and should pursue early multidisciplinary assessment and management of persisting symptoms. Addressing physical, psychological, and functional sequelae will mitigate the effect of long COVID and improve the health and quality of life of older people.

Source: Mansell V, Hall Dykgraaf S, Kidd M, Goodyear-Smith F. Long COVID and older people. Lancet Healthy Longev. 2022 Dec;3(12):e849-e854. doi: 10.1016/S2666-7568(22)00245-8. PMID: 36480981. https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(22)00245-8/fulltext (Full study)

Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2

Abstract:

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection – some have proposed that Long Covid may be a consequence of either an excessive or inadequate initial response. We analysed SARS-CoV-2 humoral and cellular immunity in healthcare workers infected during the first wave.

Symptom questionnaires allowed stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observed no difference in antibody responses to spike, RBD or nucleoprotein, virus neutralisation, or T cell responses. Also, there was no difference in the profile of antibody waning.

Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again showed similar SARS-CoV-2 immunity. Thus, quantitative differences in SARS-CoV-2 adaptive immunity during acute infection are unlikely to contribute to Long Covid causality.

Source: Altmann D, Reynolds C, Joy G, et al. Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2. Research Square; 2022. DOI: 10.21203/rs.3.rs-2324777/v1. https://www.researchsquare.com/article/rs-2324777/v1 (Full text)

Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review

Abstract:

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden.

In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition.

Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition.

Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination.

Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.

Source: Tofarides AG, Christaki E, Milionis H, Nikolopoulos GK. Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review. Life (Basel). 2022 Dec 8;12(12):2057. doi: 10.3390/life12122057. PMID: 36556422. https://www.mdpi.com/2075-1729/12/12/2057 (Full text)

The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis

Abstract:

Background: Although multiple studies have revealed that coronavirus disease 2019 (COVID-19) vaccines can reduce COVID-19-related outcomes, little is known about their impact on post-COVID-19 conditions. We performed a systematic literature review and meta-analysis on the effectiveness of COVID-19 vaccination against post-COVID-19 conditions (ie, long COVID).

Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine. A post-COVID-19 condition was defined as any symptom that was present 3 or more weeks after having COVID-19. Editorials, commentaries, reviews, study protocols, and studies in the pediatric population were excluded. We calculated the pooled diagnostic odds ratios (DORs) for post-COVID-19 conditions between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 – DOR).

Results: In total, 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post-COVID-19 conditions, of which 6 studies were included in the meta-analysis. The pooled DOR for post-COVID-19 conditions among individuals vaccinated with at least 1 dose was 0.708 (95% confidence interval (CI), 0.692-0.725) with an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%-30.8%). The vaccine effectiveness was 35.3% (95% CI, 32.3%-38.1%) among those who received the COVID-19 vaccine before having COVID-19, and 27.4% (95% CI, 25.4%-29.3%) among those who received it after having COVID-19.

Conclusions: COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low.

Source: Marra AR, Kobayashi T, Suzuki H, Alsuhaibani M, Hasegawa S, Tholany J, Perencevich E, Maezato AM, Ricardo VCV, Salinas JL, Edmond MB, Rizzo LV. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol. 2022 Dec 6;2(1):e192. doi: 10.1017/ash.2022.336. PMID: 36505947; PMCID: PMC9726631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726631/ (Full text)

The Long-COVID Experience Changed People’s Vaccine Hesitancy but Not Their Vaccination Fear

Abstract:

Starting in early 2020, the COVID-19 pandemic has been responsible, worldwide, for millions of deaths and patients with long-COVID syndrome. In an attempt to stop the spread of the virus, the blanket administration of COVID-19 vaccines proved to be the most effective measure, yet the existence and availability of functional vaccines did not and, still, do not ensure the willingness and intent of people to be vaccinated.

This study assessed the similarities and differences in vaccine fears and vaccine hesitancy through between clusters of subjects: people that were not infected with COVID-19, people that had COVID but did not develop long-lasting symptoms, and people that were infected with COVID and developed long-COVID syndrome. From the sample of 1111 Italian people, it was found that individuals who experienced mild symptoms showed higher vaccine hesitancy (confidence, complacency, and collective responsibility) than those who did not contract COVID-19. People affected by long-COVID showed a lower overall hesitancy than individuals who had COVID-19 without incurring long-lasting symptoms and, thus, essentially resembled people who had no experience of COVID-19 infection in terms of the vaccine hesitancy scores. Vaccine fear remained unchanged across all three of the examined clusters.

Source: Duradoni M, Gursesli MC, Materassi L, Serritella E, Guazzini A. The Long-COVID Experience Changed People’s Vaccine Hesitancy but Not Their Vaccination Fear. Int J Environ Res Public Health. 2022 Nov 5;19(21):14550. doi: 10.3390/ijerph192114550. PMID: 36361430; PMCID: PMC9654193. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654193/ (Full text)