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Nature Medicine Nov 2022First 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...
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.
Topics: Male; Humans; SARS-CoV-2; COVID-19; Reinfection; Hospitalization; Cohort Studies; Disease Progression
PubMed: 36357676
DOI: 10.1038/s41591-022-02051-3 -
Viruses Apr 2023Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions... (Meta-Analysis)
Meta-Analysis Review
Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The mean age of reinfected patients was 38.0 ± 6. years and females were predominant among reinfected patients (M/F = 0.8). The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients.
Topics: Humans; Female; Male; SARS-CoV-2; COVID-19; Reinfection; Cough
PubMed: 37112949
DOI: 10.3390/v15040967 -
Global Health Research and Policy Apr 2022With the continuation of the COVID-19 pandemic, some COVID-19 patients have become reinfected with the virus. Viral gene sequencing has found that some of these patients... (Review)
Review
BACKGROUND
With the continuation of the COVID-19 pandemic, some COVID-19 patients have become reinfected with the virus. Viral gene sequencing has found that some of these patients were reinfected by the different and others by same strains. This has raised concerns about the effectiveness of immunity after infection and the reliability of vaccines. To this end, we conducted a systematic review to assess the characteristics of patients with reinfection and possible causes.
METHODS
A systematic search was conducted across eight databases: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, WanFang, VIP and SinoMed from December 1, 2019 to September 1, 2021. The quality of included studies were assessed using JBI critical appraisal tools and Newcastle-Ottawa Scale.
RESULTS
This study included 50 studies from 20 countries. There were 118 cases of reinfection. Twenty-five patients were reported to have at least one complication. The shortest duration between the first infection and reinfection was 19 days and the longest was 293 days. During the first infection and reinfection, cough (51.6% and 43.9%) and fever (50% and 30.3%) were the most common symptoms respectively. Nine patients recovered, seven patients died, and five patients were hospitalized, but 97 patients' prognosis were unknown. B.1 is the most common variant strain at the first infection. B.1.1.7, B.1.128 and B.1.351 were the most common variant strains at reinfection. Thirty-three patients were infected by different strains and 9 patients were reported as being infected with the same strain.
CONCLUSIONS
Our research shows that it is possible for rehabilitated patients to be reinfected by SARS-COV-2. To date, the causes and risk factors of COVID-19 reinfection are not fully understood. For patients with reinfection, the diagnosis and management should be consistent with the treatment of the first infection. The public, including rehabilitated patients, should be fully vaccinated, wear masks in public places, and pay attention to maintaining social distance to avoid reinfection with the virus.
Topics: COVID-19; Humans; Pandemics; Reinfection; Reproducibility of Results; SARS-CoV-2
PubMed: 35488305
DOI: 10.1186/s41256-022-00245-3 -
Emerging Microbes & Infections Dec 2022SARS-CoV-2 reinfection rate is low. The relative severity of the first and second episodes of infection remains poorly studied. In this study, we aimed at assessing the...
SARS-CoV-2 reinfection rate is low. The relative severity of the first and second episodes of infection remains poorly studied. In this study, we aimed at assessing the frequency of SARS-CoV-2 reinfections and comparing the severity of the first and second episodes of infection. We retrospectively included patients with SARS-CoV-2 positive RT-PCR at least 90 days after clinical recovery from a COVID-19 episode and with at least one negative RT-PCR after the first infection. Whole genome sequencing and variant-specific RT-PCR were performed and clinical symptoms and severity of infection were retrospectively documented from medical files. A total of 209 COVID-19 reinfected patients were identified, accounting for 0.4% of positive cases diagnosed from 19 March 2020 to 24 August 2021. Serology was performed in 64 patients, of whom 39 (60.1%) had antibodies against SARS-CoV-2 when sampled at the early stage of their second infection. Only seven patients (3.4%) were infected twice with the same variant. We observed no differences in clinical presentation, hospitalization rate, and transfer to ICU when comparing the two episodes of infections. Our results suggest that the severity of the second episode of COVID-19 is in the same range as that of the first infection, including patients with antibodies.
Topics: COVID-19; Humans; Reinfection; Retrospective Studies; SARS-CoV-2; Whole Genome Sequencing
PubMed: 35264078
DOI: 10.1080/22221751.2022.2052358 -
Viruses Sep 2023Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected... (Review)
Review
Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.
Topics: Infant; Child; Female; Pregnancy; Humans; Aged; Respiratory Syncytial Virus Infections; Reinfection; Respiratory Syncytial Viruses; Immunity; Vaccines; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 37896776
DOI: 10.3390/v15101999 -
International Journal of Molecular... Aug 2023We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association... (Review)
Review
We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.
Topics: Adolescent; Child; Aged; Humans; Post-Acute COVID-19 Syndrome; SARS-CoV-2; COVID-19; Reinfection; Pandemics
PubMed: 37629143
DOI: 10.3390/ijms241612962 -
The Lancet. Infectious Diseases May 2023The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2...
BACKGROUND
The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant.
METHODS
For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case-control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605).
FINDINGS
11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1-83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4-35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4-99·2) at 12 months with primary series vaccination and 95·3% (81·9-98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5-52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0-57·3) at 6 months.
INTERPRETATION
All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected.
FUNDING
WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.
Topics: Humans; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Reinfection; Adaptive Immunity
PubMed: 36681084
DOI: 10.1016/S1473-3099(22)00801-5 -
Lancet (London, England) Mar 2023Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection.
METHODS
In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850).
FINDINGS
We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% (95% uncertainty interval [UI] 17·3-76·1) and 44·0% (26·5-65·0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% (49·8-93·6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% (24·4-51·3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% (69·7-97·5) for ancestral, alpha, and delta variants, and 88·9% (84·7-90·9) for omicron BA.1 at 40 weeks.
INTERPRETATION
Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.
FUNDING
Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.
Topics: United States; Humans; Bayes Theorem; COVID-19; Prospective Studies; Reinfection; Retrospective Studies; SARS-CoV-2
PubMed: 36930674
DOI: 10.1016/S0140-6736(22)02465-5 -
Viruses Jul 2023To study SARS-CoV-2 reinfections in health-care workers (HCWs) of the University Health Agency Giuliano-Isontina (ASUGI), covering the provinces of Trieste and Gorizia...
To study SARS-CoV-2 reinfections in health-care workers (HCWs) of the University Health Agency Giuliano-Isontina (ASUGI), covering the provinces of Trieste and Gorizia (northeastern Italy) routinely screened for SARS-CoV-2 via nasopharyngeal swab. Cohort study of HCWs (N = 8205) followed since the start of the pandemic (1 March 2020) through 31 January 2023. The risk of reinfection during the Omicron transmission period (after 30 November 2021) among HCWs previously infected by SARS-CoV-2 was estimated based on days since last dose of COVID-19 vaccine received, adjusting for age, sex, job task, workplace, number of doses of COVID-19 vaccines and number of swab tests performed. In the crude as well as adjusted incidence rate analysis, reinfections occurring 15+ days after a first dose of COVID-19 vaccine or 8+ days following a second or more dose were counted. In a highly vaccinated population, during the entire study period (1 March 2020-31 January 2023) 5253 HCWs incurred at least one SARS-CoV-2 infection, 4262 HCWs were infected only once, and 1091 were reinfected. Reinfections almost entirely (99.1% = 1071/1091) occurred after 30 November 2021, peaking in July 2022 (N = 161). Six hundred eighty-three reinfections followed a pre-Omicron primary event against 408 reinfections following an Omicron event. Reinfections during the Omicron transmission period occurred a mean of 400 ± 220 days after primary SARS-CoV-2 infection; 512 ± 205 days following a pre-Omicron primary event, as opposed to 218 ± 74 days after an Omicron primary infection. Thirty-four hospitalizations were observed, all before the Omicron wave, following 18 (0.4%) primary SARS-CoV-2 infections and 16 (1.5%) reinfections. By excluding events occurring <15 days after a first dose or <8 days after a further dose of COVID-19 vaccine, 605 reinfections followed a pre-Omicron primary event (raw incidence = 1.4 × 1000 person-days) against 404 after a primary Omicron infection (raw incidence = 0.3 × 1000 person-days). Apart from nurse aids (slightly enhanced biological risk) and academic HCWs (remarkably lower risk with pre-Omicron primary events), the effect of occupation in terms of job task and workplace was marginal. Furthermore, whilst the risk of reinfection was lower in males and HCWs < 60 years old following a pre-Omicron primary infection, HCWs aged 30-50 were more likely to be infected after an Omicron primary event. Regardless of timeline of primary SARS-CoV-2 event, the risk of reinfection decreased with higher number of doses of COVID-19 vaccines, being lowest after the second booster. In particular, VE was 16% for one dose, 51% for two doses, 76% for the booster and 92% for the second booster with a pre-Omicron primary SARS-CoV-2 event. The latter figures increased to 72%, 59%, 74% and 93%, respectively, with Omicron primary infections. : SARS-CoV-2 reinfections were frequent during the Omicron transmission period, though featured by mild or no symptoms. Whilst the impact of occupation on biological risk was relatively marginal, COVID-19 vaccination had the strongest protective effect against reinfection, with a 93% VE by second booster following an Omicron primary infection.
Topics: Male; Humans; Middle Aged; SARS-CoV-2; COVID-19 Vaccines; COVID-19; Reinfection; Cohort Studies
PubMed: 37515237
DOI: 10.3390/v15071551 -
Clinical Infectious Diseases : An... Dec 2021Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become pandemic and the duration of protective immunity to the virus is unknown. Cases of... (Review)
Review
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become pandemic and the duration of protective immunity to the virus is unknown. Cases of persons reinfected with the virus are being reported with increasing frequency. At present it is unclear how common reinfection with SARS-CoV-2 is and how long serum antibodies and virus-specific T cells persist after infection. For many other respiratory virus infections, including influenza and the seasonal coronaviruses that cause colds, serum antibodies persist for only months to a few years and reinfections are very common. Here we review what is known about the duration of immunity and reinfection with coronaviruses, including SARS-CoV-2, as well as the duration of immunity to other viruses and virus vaccines. These findings have implications for the need of continued protective measures and for vaccines for persons previously infected with SARS-CoV-2.
Topics: COVID-19; Humans; Influenza Vaccines; Pandemics; Reinfection; SARS-CoV-2
PubMed: 33338197
DOI: 10.1093/cid/ciaa1866