Lower prevalence of post-Covid-19 Condition following Omicron SARS-CoV-2 infection.

Objectives: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections. Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls. Results: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course. Conclusions: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection.

Interpretations of Studies on SARS-CoV-2 Vaccination and Post-acute COVID-19 Sequelae.

This article discusses causal interpretations of epidemiologic studies of the effects of vaccination on sequelae after acute severe acute respiratory syndrome coronavirus 2 infection. To date, researchers have tried to answer several different research questions on this topic. While some studies assessed the impact of postinfection vaccination on the presence of or recovery from post-acute coronavirus disease 2019 syndrome, others quantified the association between preinfection vaccination and postacute sequelae conditional on becoming infected. However, the latter analysis does not have a causal interpretation, except under the principal stratification framework-that is, this comparison can only be interpreted as causal for a nondiscernible stratum of the population. As the epidemiology of coronavirus disease 2019 is now nearly entirely dominated by reinfections, including in vaccinated individuals, and possibly caused by different Omicron subvariants, it has become even more important to design studies on the effects of vaccination on postacute sequelae that address precise causal questions and quantify effects corresponding to implementable interventions.

A mini review of reinfection with the SARS-CoV-2 Omicron variant.

Background: COVID-19 has caused severe morbidity and mortality worldwide. After the end of the dynamic zero-COVID policy in China in December, 2022, concerns regarding reinfection were raised while little was known due to the lack of surveillance data in this country. Aims: This study reviews the probability, risk factors, and severity of severe acute respiratory syndrome coronavirus 2 Omicron variant reinfection, as well as the interval between infections, risk of onward transmission by reinfected cases, and the role of booster vaccination against reinfection. Sources: References for this review were identified through searches of PubMed and Web of Science up to September 24, 2023. Results: The rate of reinfection ranges from 3.1% to 13.0%. Factors associated with a higher risk of reinfection include being female, having comorbidities, and being unvaccinated. Reinfection with the BA.4 or BA.5 variant occurs approximately 180 days after the initial infection. Reinfections are less clinically severe than primary infections, and there is evidence of lower transmissibility. The debate surrounding the effectiveness and feasibility of booster vaccinations in preventing reinfection continues. Conclusions: The reinfection rate during the Omicron epidemic is significantly higher than in previous epidemic periods. However, the symptoms and infectivity of reinfection were weaker than those of the prior infection. Medical staff and individuals at high risk of reinfection should be vigilant. The efficacy of booster vaccinations in reducing reinfection is currently under debate.

Who develops long COVID? Longitudinal pre-pandemic predictors of long COVID and symptom clusters in a representative Dutch population.

OBJECTIVES: Prior studies show that long COVID has a heterogeneous presentation. Whether specific risk factors are related to subclusters of long COVID remains unknown. This study aimed to determine pre-pandemic predictors of long COVID and symptom clustering. METHODS: 3022 participants of a panel representative of the Dutch population completed an online survey about long COVID symptoms. Data was merged to 2018/2019 panel data covering sociodemographic, medical, and psychosocial predictors. A total of 415 participants were classified as having long COVID. K-means clustering was used to identify patient clusters. Multivariate and lasso regression was used to identify relevant predictors compared to a COVID-19 positive control group. RESULTS: Predictors of long COVID included Western ethnicity, BMI, chronic disease, COVID-19 reinfections, severity, and symptoms, lower self-esteem, and higher positive affect (AUC=0.80, 95%CI 0.73-0.86). Four clusters were identified: a low and a high symptom severity cluster, a smell-taste and respiratory symptoms cluster, and a neuro-cognitive, psychosocial, and inflammatory symptom cluster. Predictors for the different clusters included regular health complaints, healthcare use, fear of COVID-19, anxiety, depressive symptoms, and neuroticism. CONCLUSIONS: A combination of sociodemographic, medical, and psychosocial factors predicted long COVID. Heterogenous symptom clusters suggest that there are different phenotypes of long COVID presentation.

A long-term cohort study: the immune evasion and decreasing neutralization dominated the SARS-CoV-2 breakthrough infection.

Most of vaccinees and COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, which helps preventing infection and alleviating symptoms. However, breakthrough viral infections caused by emerging SARS-CoV-2 variants, especially Omicron subvariants, still pose a serious threat to global health. By monitoring the viral infections and the sera neutralization ability of a long-tracked cohort, we found out that the immune evasion of emerging Omicron subvariants and the decreasing neutralization led to the mini-wave of SARS-CoV-2 breakthrough infections. Meanwhile, no significant difference had been found in the infectivity of tested SARS-CoV-2 variants, even though the affinity between human angiotensin-converting enzyme 2 (hACE2) and receptor-binding domain (RBDs) of tested variants showed an increasing trend. Notably, the immune imprinting of inactivated COVID-19 vaccine can be relieved by infections of BA.5.2 and XBB.1.5 variants sequentially. Our data reveal the rising reinfection risk of immune evasion variants like Omicron JN.1 in China, suggesting the importance of booster with updated vaccines.

Impact of infectious density-induced additional screening and treatment saturation on COVID-19: Modeling and cost-effective optimal control.

This study introduces a novel SI2HR model, where "I2" denotes two infectious classes representing asymptomatic and symptomatic infections, aiming to investigate and analyze the cost-effective optimal control measures for managing COVID-19. The model incorporates a novel concept of infectious density-induced additional screening (IDIAS) and accounts for treatment saturation. Furthermore, the model considers the possibility of reinfection and the loss of immunity in individuals who have previously recovered. To validate and calibrate the proposed model, real data from November-December 2022 in Hong Kong are utilized. The estimated parameters obtained from this calibration process are valuable for prediction purposes and facilitate further numerical simulations. An analysis of the model reveals that delays in screening, treatment, and quarantine contribute to an increase in the basic reproduction number R0, indicating a tendency towards endemicity. In particular, from the elasticity of R0, we deduce that normalized sensitivity indices of baseline screening rate (θ), quarantine rates (γ, αs), and treatment rate (α) are negative, which shows that delaying any of these may cause huge surge in R0, ultimately increases the disease burden. Further, by the contour plots, we note the two-parameter behavior of the infectives (both symptomatic and asymptomatic). Expanding upon the model analysis, an optimal control problem (OCP) is formulated, incorporating three control measures: precautionary interventions, boosted IDIAS, and boosted treatment. The Pontryagin's maximum principle and the forward-backward sweep method are employed to solve the OCP. The numerical simulations highlight that enhanced screening and treatment, coupled with preventive interventions, can effectively contribute to sustainable disease control. However, the cost-effectiveness analysis (CEA) conducted in this study suggests that boosting IDIAS alone is the most economically efficient and cost-effective approach compared to other strategies. The CEA results provide valuable insights into identifying specific strategies based on their cost-efficacy ranking, which can be implemented to maximize impact while minimizing costs. Overall, this research offers significant insights for policymakers and healthcare professionals, providing a framework to optimize control efforts for COVID-19 or similar epidemics in the future.

Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant.

Overall effectiveness of infection in preventing reinfection with SARS-CoV-2 JN.1 variant was estimated at 1.8% (95% CI: -9.3-12.6%), and demonstrated rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9 to 94.7%) within 3 to less than 6 months, to a negligible level after one year.

Relative frequency of genomic mutations in SARS-CoV-2 recovered from southern Brazilian cases of COVID-19 through the Gamma, Delta and Omicron waves.

The presence of different mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can be related to changes in coronavirus disease (COVID-19) infection. Besides, these viral alterations associated with factors such as massive number of positive cases, vaccination and reinfections can be important in the viral evolution process. As well as, mutations found at low frequencies may have a more neutral action and consequently be less inclined to negative selection, facilitating their spread through the population. Related to that, we aimed to present mutations that are possibly relevant in the process of viral evolution found in 115 SARS-CoV-2 sequences from samples of individuals residing in the metropolitan region of Porto Alegre in the state of Rio Grande do Sul, Brazil. The genome from clinical samples was sequenced using High-Throughput Sequencing (HTS) and analyzed using a workflow to map reads and find variations/SNPs. The samples were separated into 3 groups considering the sample lineage. Of the total number of analyzed sequences, 35 were from the Gamma lineage, 35 from Delta and 45 from Omicron. Amino acid changes present in frequencies lower than 80% of the reads in the sequences were evaluated. 11 common mutations among the samples were found in the Gamma lineage, 1 in the ORF1ab gene, 7 in the S gene, 2 in the ORF6 gene and 1 in the ORF7a gene. While in the Delta lineage, a total of 11 mutations distributed in the ORF1ab, S, ORF7a and N genes, 2, 7, 1 and 1 mutation were found in each gene, respectively. And finally, in the Omicron, 16 mutations were identified, 2 in the ORF1ab gene, 12 in the S gene and 2 in the M gene. In conclusion, we emphasize that genomic surveillance can be a useful tool to assess how mutations play a key role in virus adaptation, and its process of susceptibility to new hosts showing the possible signs of viral evolution.

Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.

The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.

Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study.

OBJECTIVES: To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. METHODS: IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2-5 weeks post-immunisation. RESULTS: Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). CONCLUSION: Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. TRIAL REGISTRATION NUMBER: NCT04798625.

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection.

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-ß, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

Comparison of COVID-19 Symptoms in Correctional Health Care Workers During the Initial and Omicron Surges.

There is a dearth of medical literature that characterizes the experience of correctional health care workers (HCWs) during the COVID-19 pandemic. We performed a retrospective chart review of the results of an ongoing universal SARS-CoV-2 testing program for New Jersey correctional system HCWs and describe their presenting symptoms, perceived exposure, and demographic characteristics during the initial (March 15, 2020, to August 31, 2020) and Omicron (March 1, 2022, to August 31, 2022) COVID-19 surges. Analysis included 123 eligible records. In both surges, nurses had a high proportion of infections and cough was the most commonly reported symptom. Fever was more than twice as commonly reported in the initial surge. During the Omicron surge, nasal symptoms predominated (39.5% [95% CI: 28.4-51.4]) compared with the initial surge (8.5% [95% CI: 2.4-20.4]). Perceived exposure source was predominantly work related during the initial surge and multiple other sources of exposure were identified during the Omicron surge. Ninety-six percent of HCWs received a COVID-19 booster shot by February 2022. The reinfection rate was less than 10% for our initial cohort. Presenting symptoms correlated with the circulating variant. Mass vaccination of staff, the lower virulence of the Omicron variant, and possibly prior infection likely contributed to the milder illness experienced during the Omicron surge.

Adverse Events Following COVISHIELD and VERO CELL Vaccination Campaigns Against COVID-19.

BACKGROUND: Vaccination against COVID-19 for Nepalese was initiated in January 2021 for various age groups. People were anxious about receiving the vaccines and were concerned about the safety profile of the vaccine they received. In this study, we have tried to observe the Adverse Events Following Immunization of two different vaccines namely COVISHIELD (ChAdOx1 nCOV-19) and VERO CELL (CZ02 strain), used in different phases of vaccination by the government of Nepal. METHODS: We conducted a cross-sectional study among people who received COVID-19 vaccines in this study using a self-administered questionnaire.  Data was cleaned and then exported to IBM SPSS v.20 for analysis, Chi-square test was used to see the association between different variables and a p-value<0.05 was considered statistically significant. RESULTS: Out of 303 respondents, all had received the first and 270 participants had received the second dose of the COVID-19 vaccine, among which, 133 (43.89%) reported at least one side effect after the first dose of vaccination while 58 (21.48%) had self-reported side effects after the second dose of vaccination. Seventeen percent of the respondents had COVID-19 infection within the past 3 months before receiving COVID-19 vaccine. Three percent of participants had re-infection with COVID-19 after receiving the first or the second dose of the COVID-19 vaccine. Among participants who experienced adverse events, 42% and 62.1% of participants experienced mild adverse events following the first dose and second dose of the vaccine, respectively.  Conclusions: The adverse events following immunization for both vaccines after both doses of vaccination were quite low, with 43.89% of participants reporting side effects after the first dose and 21.48% of participants reporting side effects after the second dose. Adverse events were most frequently reported within 24 hours of vaccination and were mostly mild. There was no statistical significance of adverse events between both vaccines.

Long-term outcomes of hospitalized patients with SARS-CoV-2/COVID-19 with and without neurological involvement: 3-year follow-up assessment.

BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.

Crucial role played by CK8+ cells in mediating alveolar injury remodeling for patients with COVID-19.

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

COVID-19 in City Council Civil Servants, 1 March 2020-31 January 2023: Risk of Infection, Reinfection, Vaccine Effectiveness and the Impact of Heterologous Triple Vaccination.

Background: The risk of COVID-19 increases in any occupation entailing intense social interactions. This study aimed to investigate the impact of COVID-19 among civil servants of Trieste city council (northeastern Italy) over the entire pandemic. Methods: The crude incidence rate of COVID-19 was estimated from 1 March 2020 to 31 January 2023 by explanatory factors, expressing the estimate as COVID-19 events x 10,000 person-days (P-d) at risk. A multivariable Cox proportional hazard regression model was fitted to examine the risk of primary COVID-19 infection and reinfections, reporting adjusted hazard ratios (aHR) with 95% confidence interval (95% CI). Results: The cohort of Trieste city council was mainly composed of administrative clerks (48.5%), nursery teachers (33%), technicians (9.9%) and local police officers (8.5%). Between 1 March 2020 and 31 January 2023, 1444 (62.4%) employees tested positive for SARS-CoV-2 at least once and 18.1% (=262/1444) at least twice. By the end of this study, 55% (N = 1272) of employees had received at least three doses of COVID-19 vaccine, whereas 19.7% (N = 457) remained unvaccinated. At multiple Cox regression analysis, the adjusted risk of primary COVID-19 events during the entire study period increased in employees aged 40-49 years (aHR = 1.65; 95% CI: 1.01; 2.71), females (aHR = 1.28; 95%CI: 1.12; 1.45), local police officers (aHR = 1.82; 95%CI: 1.50; 2.22) and nursery teachers (aHR = 1.27; 95%CI: 1.13; 1.43). However, whilst the risk of primary infections in police officers increased already during the Alpha transmission period (aHR = 6.82; 95%CI: 4.48; 10.40), progressively reducing across subsequent variants, for nursery teachers, it increased during the Delta wave (aHR = 2.42; 1.70; 3.44), reducing with Omicron (aHR = 1.23; 95%CI: 1.07; 1.40). Compared to unvaccinated colleagues, during the entire study period the risk of primary infections was significantly lower in employees immunized with three (aHR = 0.42; 95%CI: 0.36; 0.47) or four (aHR = 0.30; 95%CI: 0.23; 0.40) doses of COVID-19 vaccine, for a vaccine effectiveness (VE) of 58% and 70%, respectively. The protective effect of vaccination against primary infections was confirmed in the sub-group analysis by main pandemic waves, for a VE of 75% for one dose against 99% for two doses during the Alpha transmission period, slightly reducing to 59% and 70% in Delta time, respectively. During the Omicron wave, the risk of primary SARS-CoV-2 infections diminished significantly with three (aHR = 0.42; 95%CI: 0.36; 0.49) or four vaccine doses (aHR = 0.09; 95%CI: 0.05; 0.16), for a VE of 58% and 91%, respectively. Moreover, the risk of primary SARS-CoV-2 reinfections during the entire study period reduced with one (aHR = 0.47; 95%CI: 0.27; 0.82), two (aHR = 0.42; 95%CI: 0.30; 0.58), three (aHR = 0.32; 95%CI: 0.24; 0.44) or four vaccine doses (aHR = 0.14; 95%CI: 0.05; 0.46), for a VE of 53%, 58%, 68% and 86% against reinfections, respectively. No significant difference in VE was associated with heterologous versus homologous triple vaccination, both against primary infections or reinfections. Conclusions: Primary SARS-CoV-2 infections were more likely among nursery teachers and local police officers. The risk of both primary infections and reinfections reduced with higher number of doses of COVID-19 vaccine, regardless of the pandemic wave. Since city council civil servants were swab tested on demand or for contact tracing, the estimation of COVID-19 risk and VE largely missed aymptomatic SARS-CoV-2 infections. On the one hand, the present study confirmed the protective effect of COVID-19 vaccination against symptomatic SARS-CoV-2 infections; on the other hand, it highlighted not only the importance of continuous booster doses to keep up the humoral immunity over time but also the importance of updated vaccine formulations to prevent and control the spread of a highly mutable virus. Moreover, the protective effect of the first two doses against reinfections confirmed the efficacy of hybrid immunity during Omicron time.

Stuck in pandemic uncertainty: a review of the persistent effects of COVID-19 infection in immune-deficient people.

BACKGROUND: People who are immune-deficient/disordered (IDP) are underrepresented in COVID-19 studies. Specifically, there is limited research on post-SARS-CoV-2 infection outcomes, including viral persistence and long-term sequelae in these populations. OBJECTIVES: This review aimed to examine the published literature on the occurrence of persistent SARS-CoV-2 positivity, relapse, reinfections, variant coinfection, and post-acute sequelae of COVID-19 in IDP. Although the available literature largely centred on those with secondary immunodeficiencies, studies on people with inborn errors of immunity are also included. SOURCES: PubMed was searched using medical subject headings terms to identify relevant articles from the last 4 years. Articles on primary and secondary immunodeficiencies were chosen, and a special emphasis was placed on including articles that studied people with inborn errors of immunity. The absence of extensive cohort studies including these individuals has limited most articles in this review to case reports, whereas the articles focusing on secondary immunodeficiencies include larger cohort, case-control, and cross-sectional studies. Articles focusing solely on HIV/AIDS were excluded. CONTENT: Scientific literature suggests that IDP of any age are more likely to experience persistent SARS-CoV-2 infections. Although adult IDP exhibits a higher rate of post-acute sequelae of COVID-19, milder COVID-19 infections in children may reduce their risk of experiencing post-acute sequelae of COVID-19. Reinfections and coinfections may occur at a slightly higher rate in IDP than in the general population. IMPLICATIONS: Although IDP experience increased viral persistence and inter-host evolution, it is unlikely that enough evidence can be generated at the population-level to support or refute the hypothesis that infections in IDP are significantly more likely to result in variants of concern than infections in the general population. Additional research on the relationship between viral persistence and the rate of long-term sequelae in IDP could inform the understanding of the immune response to SARS-CoV-2 in IDP and the general population.

Modelling the unexpected dynamics of COVID-19 in Manaus, Brazil.

In late March 2020, SARS-CoV-2 arrived in Manaus, Brazil, and rapidly developed into a large-scale epidemic that collapsed the local health system and resulted in extreme death rates. Several key studies reported that ∼76% of residents of Manaus were infected (attack rate AR≃76%) by October 2020, suggesting protective herd immunity had been reached. Despite this, an unexpected second wave of COVID-19 struck again in November and proved to be larger than the first, creating a catastrophe for the unprepared population. It has been suggested that this could be possible if the second wave was driven by reinfections. However, it is widely reported that reinfections were at a low rate (before the emergence of Omicron), and reinfections tend to be mild. Here, we use novel methods to model the epidemic from mortality data without considering reinfection-caused deaths and evaluate the impact of interventions to explain why the second wave appeared. The method fits a "flexible" reproductive number R0(t) that changes over the epidemic, and it is demonstrated that the method can successfully reconstruct R0(t) from simulated data. For Manaus, the method finds AR≃34% by October 2020 for the first wave, which is far less than required for herd immunity yet in-line with seroprevalence estimates. The work is complemented by a two-strain model. Using genomic data, the model estimates transmissibility of the new P.1 virus lineage as 1.9 times higher than that of the non-P.1. Moreover, an age class model variant that considers the high mortality rates of older adults show very similar results. These models thus provide a reasonable explanation for the two-wave dynamics in Manaus without the need to rely on large reinfection rates, which until now have only been found in negligible to moderate numbers in recent surveillance efforts.

Outcomes of COVID-19 re-infections: a single-center cohort of 167 patients with systemic rheumatic diseases.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls.