Does misclassification of former tobacco smokers explain the 'smoker's paradox' in the risk of COVID-19? Insights from the Stockholm Public Health Cohort.

BACKGROUND: The association between tobacco smoking and the risk of COVID-19 and its adverse outcomes is controversial, as studies reported contrasting findings. Bias due to misclassification of the exposure in the analyses of current versus non-current smoking could be a possible explanation because former smokers may have higher background risks of the disease due to co-morbidity. The aim of the study was to investigate the extent of this potential bias by separating non-, former, and current smokers when assessing the risk or prognosis of diseases. METHODS: We analysed data from 43,400 participants in the Stockholm Public Health Cohort, Sweden, with information on smoking obtained prior to the pandemic. We estimated the risk of COVID-19, hospital admissions and death for (a) former and current smokers relative to non-smokers, (b) current smokers relative to non-current smokers, that is, including former smokers; adjusting for potential confounders (aRR). RESULTS: The aRR of a COVID-19 diagnosis was elevated for former smokers compared with non-smokers (1.07; 95% confidence interval (CI) =1.00-1.15); including hospital admission with any COVID-19 diagnosis (aRR= 1.23; 95% CI = 1.03-1.48); or with COVID-19 as the main diagnosis (aRR=1.23, 95% CI= 1.01-1.49); and death within 30 days with COVID-19 as the main or a contributory cause (aRR=1.40; 95% CI=1.00-1.95). Current smoking was negatively associated with risk of COVID-19 (aRR=0.79; 95% CI=0.68-0.91). CONCLUSIONS: Separating non-smokers from former smokers when assessing the disease risk or prognosis is essential to avoid bias. However, the negative association between current smoking and the risk of COVID-19 could not be entirely explained by misclassification.

Effectiveness of messenger RNA vaccines against infection with SARS-CoV-2 during the periods of Delta and Omicron variant predominance in Japan: the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study.

OBJECTIVES: We aimed to evaluate COVID-19 messenger RNA vaccine effectiveness during the Delta- and Omicron-predominant periods in Japan. METHODS: We conducted a population-based cohort study among individuals aged 16-64 years during two periods: the Delta-predominant period (July 1-December 31, 2021) and the Omicron-predominant period (January 1-March 29, 2022). RESULTS: When comparing individuals who were vaccinated with those who were unvaccinated, the effectiveness of a second dose against symptomatic infection was 89.8% (95% confidence interval [CI]: 80.5-94.7%) during the Delta-predominant period and 21.2% (95% CI: 11.0-30.3%) during the Omicron-predominant period. The effectiveness of a third dose against symptomatic infection was 71.8% (95% CI: 60.1-80.1%) during the Omicron-predominant period. CONCLUSION: Vaccine effectiveness against symptomatic infection decreased during the Omicron-predominant period but was maintained by a third dose.

Socio-Demographic Factors Associated With COVID-19 Vaccine Hesitancy Among Middle-Aged Adults During the Quebec's Vaccination Campaign.

Introduction: The objective of this study was to characterize the combinations of demographic and socioeconomic characteristics associated to the unwillingness to receive the COVID-19 vaccines during the 2021 Quebec's vaccination campaign. Materials and Methods: In March-June 2021, we conducted an online survey of the participants of the CARTaGENE population-based cohort, composed of middle-aged and older adults. After comparing the vaccinated and unvaccinated participants, we investigated vaccine hesitancy among participants who were unvaccinated. For identifying homogeneous groups of individuals with respect to vaccine hesitancy, we used a machine learning approach based on a hybrid tree-based model. Results: Among the 6,105 participants of the vaccine cohort, 3,553 (58.2%) had at least one dose of COVID-19 vaccine. Among the 2,552 participants, 221 (8.7%) did not want to be vaccinated (91) or were uncertain (130). The median age for the unvaccinated participants was 59.3 years [IQR 54.7-63.9]. The optimal hybrid tree-based model identified seven groups. Individuals having a household income lower than $100,000 and being born outside of Canada had the highest rate of vaccine hesitancy (28% [95% CI 19.8-36.3]). For those born in Canada, the vaccine hesitancy rate among the individuals who have a household income below $50,000 before the pandemic or are Non-retired was of 12.1% [95% CI 8.7-15.5] and 10.6% [95% CI 7.6-13.7], respectively. For the participants with a high household income before the pandemic (more than $100,000) and a low level of education, those who experienced a loss of income during the pandemic had a high level of hesitancy (19.2% [8.5-29.9]) whereas others who did not experience a loss of income had a lower level of hesitancy (6.0% [2.8-9.2]). For the other groups, the level of hesitancy was low of around 3% (3.2% [95% CI 1.9-4.4] and 3.4% [95% CI 1.5-5.2]). Discussion: Public health initiatives to tackle vaccine hesitancy should take into account these socio-economic determinants and deliver personalized messages toward people having socio-economic difficulties and/or being part of socio-cultural minorities.

Role of the AB0 blood group in COVID-19 infection and complications: A population-based study.

Since the beginning of the COVID-19 pandemic, the ABO blood group has been described as a possible biological marker of susceptibility for the disease. This study evaluates the role of ABO group on the risk of SARS-CoV-2 infection and related complications in a population-based cohort including 87,090 subjects from the Navarre population (Northern Spain) with no history of SARS-CoV-2 infection and with known ABO blood group, after one year of the pandemic (May 2020 - May 2021). The risk of infection, hospitalization, Intensive Care Unit (ICU) admission and death was analyzed using multivariate logistic regression, adjusting for possible confounding variables. A lower risk of infection was observed in group 0 vs non-0 groups [OR 0.94 (95 %CI 0.90-0.99)], a higher risk of infection in group A vs non-A groups [OR 1.09 (95 %CI 1.04-1.15)] and a higher risk of infection in group A vs group 0 [OR 1.08 (95CI 1.03-1.14)] (when the 4 groups are analyzed separately). No association was observed between blood groups and hospitalization, ICU admission, or death in SARS-CoV-2 infected subjects. Regarding the risk of SARS-CoV-2 infection, we observed a protective role of group O and a greater risk in the A group.

Comparative Immunogenicity of COVID-19 Vaccines in a Population-Based Cohort Study with SARS-CoV-2-Infected and Uninfected Participants.

To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants of the Tirschenreuth county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, or Spikevax had median neutralizing antibody titers ranging from ID50 = 25 to 75. Individuals with two immunizations with Comirnaty or Spikevax had higher median ID50s (of 253 and 554, respectively). Regression analysis indicated that both increased age and increased time since vaccination independently decreased RBD binding and neutralizing antibody levels. Unvaccinated participants with detectable N-antibodies at baseline (June 2020) revealed a median ID50 of 72 at the April 2021 follow-up. Previously infected participants that received one dose of Vaxzevria or Comirnaty had median ID50 to 929 and 2502, respectively. Individuals with a second dose of Comirnaty given in a three-week interval after the first dose did not have higher median antibody levels than individuals with one dose. Prior infection also primed for high systemic IgA levels in response to one dose of Comirnaty that exceeded IgA levels observed after two doses of Comirnaty in previously uninfected participants. Neutralizing antibody levels targeting the spike protein of Beta and Delta variants were diminished compared to the wild type in vaccinated and infected participants.

SARS-CoV-2-specific B- and T-cell immunity in a population-based study of young Swedish adults.

BACKGROUND: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear. OBJECTIVE: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults. METHODS: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot. RESULTS: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects. CONCLUSIONS: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Swab and Sputum SARS-CoV-2 RNA-Negative, CT-Positive, Symptomatic Contacts of COVID-19 Cases: A Hypothesis-Generating Prospective Population-Based Cohort Study of Eight Clusters.

Background: While some contacts of COVID-19 cases become symptomatic and radiographically abnormal, their SARS-CoV-2 RNA tests remain negative throughout the disease course. This prospective population-based cohort study aimed to explore their characteristics and significances. Methods: From January 22, 2020, when the first COVID-19 case was identified in Hefei, China, until July 3, a total of 14,839 people in Feidong, Hefei, with a population of ~1,081,000 underwent SARS-CoV-2 RNA testing, where 36 cases (0.2%) with confirmed COVID-19 infection (Group 1) and 27 close contacts (0.2%) testing negative for SARS-CoV-2 RNA but having both positive COVID-19 exposure histories and CT findings (Group 2) from eight clusters were prospectively identified. Another 62 non-COVID-19 pneumonia cases without any exposure history (Group 3) were enrolled, and characteristics of the three groups were described and compared. We further described a cluster with an unusual transmission pattern. Results: Fever was more common in Group 2 than Groups 1 and 3. Frequency of diarrhea in Group 1 was higher than in Groups 2 and 3. Median leucocyte, neutrophil, monocyte, and eosinophil counts were all lower in Groups 1 and 2 than in Group 3. Median D-dimer level was lower in Group 1 than in Groups 2 and 3. Total protein and albumin levels were higher in Groups 1 and 2 than in Group 3. C-reactive protein level was lower and erythrocyte sedimentation rate slower in Groups 1 and 2 than in Group 3. Combination antibacterial therapy and levofloxacin were more often used in Group 3 than in Groups 1 and 2. Lopinavir/ritonavir was more often administered in Groups 1 and 2 than in Group 3. Group 1 received more often corticosteroids than Groups 2 and 3. Group 2 received less often oxygen therapy than Groups 1 and 3. Median duration from illness onset to discharge was longer in Group 1 (27 d) than Groups 2 and 3 (both 17 d). Among contacts of a confirmed COVID-19 patient, only one had a positive virus RNA test but remained asymptomatic and had negative CT findings, and three had negative virus RNA tests but had symptoms and positive CT findings, one of whom transmitted COVID-19 to another asymptomatic laboratory-confirmed patient who had no other exposures. Conclusions: Among close contacts of confirmed COVID-19 cases, some present with positive symptoms and CT findings but test negative for SARS-CoV-2 RNA using common respiratory (throat swab and sputum) specimens; they have features more similar to confirmed COVID-19 cases than non-COVID-19 pneumonia cases and might have transmitted SARS-CoV-2 to others. Such cases might add to the complexity and difficulty of COVID-19 control. Our hypothesis-generating study might suggest that SARS-CoV-2 RNA testing by rRT-PCR assays of common respiratory (throat swab and sputum) specimens alone, the widely accepted "golden standard" for diagnosing COVID-19, might be sometimes insufficient, and that further studies with some further procedures (e.g., testing via bronchoalveolar lavage or specific antibodies) would be warranted for Group 2-like patients, namely, the SARS-CoV-2 RNA-negative (tested using common respiratory specimens), radiographically positive, symptomatic contacts of COVID-19 cases, to further reveal their nature.

Epidemiological characteristics of the COVID-19 spring outbreak in Quebec, Canada: a population-based study.

BACKGROUND: By mid-July 2020, more than 108,000 COVID-19 cases had been diagnosed in Canada with more than half in the province of Quebec. In this context, we launched a study to analyze the epidemiological characteristics and the socio-economic impact of the spring outbreak in the population. METHOD: We conducted an online survey of the participants of the CARTaGENE population-based cohort, composed of middle-aged and older adults. We collected information on socio-demographic, lifestyle, health condition, COVID-19 related symptoms and COVID-19 testing. We studied the association between these factors and two outcomes: the status of having been tested for SARS-CoV-2 and the status of having received a positive test. These associations were measured with univariate and multivariate analyses using a hybrid tree-based regression model. RESULTS: Among the 8,129 respondents from the CARTaGENE cohort, 649 were tested for COVID-19 and 41 were positive. Medical workers and individuals having a contact with a COVID-19 patient had the highest probabilities of being tested (32% and 42.4%, respectively) and of being positive (17.2% and 13.0%, respectively) among those tested. Approximately 8% of the participants declared that they have experienced at least one of the four COVID-19 related symptoms chosen by the Public Health authorities (fever, cough, dyspnea, anosmia) but were not tested. Results from the tree-based model analyses adjusted on exposure factors showed that the combination of dyspnea, dry cough and fever was highly associated with being tested whereas anosmia, fever, and headache were the most discriminant factors for having a positive test among those tested. During the spring outbreak, more than one third of the participants have experienced a decrease in access to health services. There were gender and age differences in the socio-economic and emotional impacts of the pandemic. CONCLUSION: We have shown some discrepancies between the symptoms associated with being tested and being positive. In particular, the anosmia is a major discriminant symptom for positivity whereas ear-nose-throat symptoms seem not to be COVID-19 related. The results also emphasize the need of increasing the accessibility of testing for the general population.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich.

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

BACKGROUND: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China. METHODS: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated. FINDINGS: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (-8.8 days, 95%CI -9.7, -7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (-2.35 days, 95%CI -3.65, -1.06) compared to interferon-beta-1b monotherapy. INTERPRETATION: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients. FUNDING: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.