Developing transmissible vaccines for animal infections.

Intrinsically safe designs and a staged transparent development process will be essential.

A dataset of small-mammal detections in West Africa and their associated micro-organisms.

Rodents, a globally distributed and ecologically important mammalian order, serve as hosts for various zoonotic pathogens. However, sampling of rodents and their pathogens suffers from taxonomic and spatial biases. This affects consolidated databases, such as IUCN and GBIF, limiting inference regarding the spillover hazard of zoonotic pathogens into human populations. Here, we synthesised data from 127 rodent trapping studies conducted in 14 West African countries between 1964 and 2022. We combined occurrence data with pathogen screening results to produce a dataset containing detection/non-detection data for 65,628 individual small mammals identified to the species level from at least 1,611 trapping sites. We also included 32 microorganisms, identified to the species or genus levels, that are known or potential pathogens. The dataset is formatted to Darwin Core Standard with associated metadata. This dataset can mitigate spatial and taxonomic biases of current databases, improving understanding of rodent-associated zoonotic pathogen spillover across West Africa.

Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa fever endemic regions.

Lassa fever (LF) is a potentially lethal viral haemorrhagic infection of humans caused by Lassa mammarenavirus (LASV). It is an important endemic zoonotic disease in West Africa with growing evidence for increasing frequency and sizes of outbreaks. Phylogeographic and molecular epidemiology methods have projected expansion of the Lassa fever endemic zone in the context of future global change. The Natal multimammate mouse (Mastomys natalensis) is the predominant LASV reservoir, with few studies investigating the role of other animal species. To explore host sequencing biases, all LASV nucleotide sequences and associated metadata available on GenBank (n = 2,298) were retrieved. Most data originated from Nigeria (54%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited and only 69 sequences encompassed complete genes. We found a strong positive correlation between the number of confirmed human cases and sequences at the country level (r = 0.93 (95% Confidence Interval = 0.71-0.98), p < 0.001) but no correlation exists between confirmed cases and the number of available rodent sequences (r = -0.019 (95% C.I. -0.71-0.69), p = 0.96). Spatial modelling of sequencing effort highlighted current biases in locations of available sequences, with increased sequencing effort observed in Southern Guinea and Southern Nigeria. Phylogenetic analyses showed geographic clustering of LASV lineages, suggestive of isolated events of human-to-rodent transmission and the emergence of currently circulating strains of LASV from the year 1498 in Nigeria. Overall, the current study highlights significant geographic limitations in LASV surveillance, particularly, in non-human hosts. Further investigation of the non-human reservoir of LASV, alongside expanded surveillance, are required for precise characterisation of the emergence and dispersal of LASV. Accurate surveillance of LASV circulation in non-human hosts is vital to guide early detection and initiation of public health interventions for future Lassa fever outbreaks.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Classification of Lapses in Smokers Attempting to Stop: A Supervised Machine Learning Approach Using Data From a Popular Smoking Cessation Smartphone App.

INTRODUCTION: Smoking lapses after the quit date often lead to full relapse. To inform the development of real time, tailored lapse prevention support, we used observational data from a popular smoking cessation app to develop supervised machine learning algorithms to distinguish lapse from non-lapse reports. AIMS AND METHODS: We used data from app users with ≥20 unprompted data entries, which included information about craving severity, mood, activity, social context, and lapse incidence. A series of group-level supervised machine learning algorithms (eg, Random Forest, XGBoost) were trained and tested. Their ability to classify lapses for out-of-sample (1) observations and (2) individuals were evaluated. Next, a series of individual-level and hybrid algorithms were trained and tested. RESULTS: Participants (N = 791) provided 37 002 data entries (7.6% lapses). The best-performing group-level algorithm had an area under the receiver operating characteristic curve (AUC) of 0.969 (95% confidence interval [CI] = 0.961 to 0.978). Its ability to classify lapses for out-of-sample individuals ranged from poor to excellent (AUC = 0.482-1.000). Individual-level algorithms could be constructed for 39/791 participants with sufficient data, with a median AUC of 0.938 (range: 0.518-1.000). Hybrid algorithms could be constructed for 184/791 participants and had a median AUC of 0.825 (range: 0.375-1.000). CONCLUSIONS: Using unprompted app data appeared feasible for constructing a high-performing group-level lapse classification algorithm but its performance was variable when applied to unseen individuals. Algorithms trained on each individual's dataset, in addition to hybrid algorithms trained on the group plus a proportion of each individual's data, had improved performance but could only be constructed for a minority of participants. IMPLICATIONS: This study used routinely collected data from a popular smartphone app to train and test a series of supervised machine learning algorithms to distinguish lapse from non-lapse events. Although a high-performing group-level algorithm was developed, it had variable performance when applied to new, unseen individuals. Individual-level and hybrid algorithms had somewhat greater performance but could not be constructed for all participants because of the lack of variability in the outcome measure. Triangulation of results with those from a prompted study design is recommended prior to intervention development, with real-world lapse prediction likely requiring a balance between unprompted and prompted app data.

Rodent trapping studies as an overlooked information source for understanding endemic and novel zoonotic spillover.

Rodents, a diverse, globally distributed and ecologically important order of mammals are nevertheless important reservoirs of known and novel zoonotic pathogens. Ongoing anthropogenic land use change is altering these species' abundance and distribution, which among zoonotic host species may increase the risk of zoonoses spillover events. A better understanding of the current distribution of rodent species is required to guide attempts to mitigate against potentially increased zoonotic disease hazard and risk. However, available species distribution and host-pathogen association datasets (e.g. IUCN, GBIF, CLOVER) are often taxonomically and spatially biased. Here, we synthesise data from West Africa from 127 rodent trapping studies, published between 1964-2022, as an additional source of information to characterise the range and presence of rodent species and identify the subgroup of species that are potential or known pathogen hosts. We identify that these rodent trapping studies, although biased towards human dominated landscapes across West Africa, can usefully complement current rodent species distribution datasets and we calculate the discrepancies between these datasets. For five regionally important zoonotic pathogens (Arenaviridae spp., Borrelia spp., Lassa mammarenavirus, Leptospira spp. and Toxoplasma gondii), we identify host-pathogen associations that have not been previously reported in host-association datasets. Finally, for these five pathogen groups, we find that the proportion of a rodent hosts range that have been sampled remains small with geographic clustering. A priority should be to sample rodent hosts across a greater geographic range to better characterise current and future risk of zoonotic spillover events. In the interim, studies of spatial pathogen risk informed by rodent distributions must incorporate a measure of the current sampling biases. The current synthesis of contextually rich rodent trapping data enriches available information from IUCN, GBIF and CLOVER which can support a more complete understanding of the hazard of zoonotic spillover events.

Lassa fever cases suffer from severe underreporting based on reported fatalities.

BACKGROUND: Lassa fever is a viral haemorrhagic fever endemic to eight West African countries. Symptomatic disease is expected to occur in 20% of those infected and transmission typically occurs from viral spillover from rodent hosts. The combination of limited access to diagnostics and healthcare means the true burden of this disease is unknown. METHODS: The case fatality rate among confirmed, probable and possible cases of Lassa fever in endemic regions is expected to be ≈15%. Here, annual reported cases and deaths have been used to estimate the case fatality rate, using three subsets of available data, to understand the scale of underreporting of severe human cases. RESULTS: The literature review produced 38 records of cases and fatalities, comprising 5230 reported cases and 1482 reported deaths in seven countries. The estimated case fatality rate ranges from 16.5 to 25.6% (standard deviation 11.5-32.2). The expected number of severe cases between 2012 and 2022 is 8995, with current reported numbers 58% of what is expected. CONCLUSION: This analysis highlights current uncertainty and systemic underreporting of the morbidity and mortality burden of Lassa fever in its endemic region and must be considered when discussing the epidemiology of this neglected tropical disease.

Improved Uranium Particle Analysis by SIMS using O3 - Primary Ions.

We have investigated the use of negative molecular oxygen primary ion beams (i.e., O2 - and O3 -) to determine the benefits of using such beams for uranium particle SIMS analyses. Typically, O- is the most practical negative primary ion species from the conventional duoplasmatron ion source for both age dating and uranium isotopic analysis of particles. Newer RF plasma ion sources make it possible to use O2 - and O3 - due to higher brightness and primary ion fluence, and the increased abundance of molecular species in the plasma relative to the duoplasmatron. We have determined that by using an O3 - beam, the ionization yield can be increased by a factor of approximately two over an O- beam, up to 4.7%, a substantial improvement that positively impacts measurement precision and detection limits. We also investigated the effect of the molecular oxygen beams on uranium isotope mass fractionation and the Th/U relative sensitivity factor for SIMS analyses in comparison to O- beams. We found that O3 - reduced instrumental mass fractionation and matrix/substrate effects relative to the other negative ion beams. Particle measurements using O3 - were improved compared to conventional O- beam analyses due to higher yields, smaller corrections, and reduced substrate effects.

Community transmission of monkeypox in the United Kingdom, April to May 2022.

Between 7 and 25 May, 86 monkeypox cases were confirmed in the United Kingdom (UK). Only one case is known to have travelled to a monkeypox virus (MPXV) endemic country. Seventy-nine cases with information were male and 66 reported being gay, bisexual, or other men who have sex with men. This is the first reported sustained MPXV transmission in the UK, with human-to-human transmission through close contacts, including in sexual networks. Improving case ascertainment and onward-transmission preventive measures are ongoing.

Increased outbreaks of monkeypox highlight gaps in actual disease burden in Sub-Saharan Africa and in animal reservoirs.

We explain research gaps on Monkeypox (MPX) virus epidemiology in endemic countries and present hypotheses for the recent increase of MPX cases in West Africa as a possible explanation for the current epidemic in Europe, America, and Australia. The detection of >400 MPX cases in less than a month in May 2022, across many countries underscores the epidemic potential of MPX in humans and demonstrates several important research gaps. First, the true burden of MPX in West and Central Africa is poorly understood, although it is critical for prevention and control of future outbreaks. Second, the diversity and extent of the animal reservoir remain unknown. We hypothesize that the synanthropic rodent population has increased in recent years in Africa leading to more human-rodent interactions and thus increased transmission of MPXV. We further hypothesise that nearly 45 years after the end of routine smallpox vaccination, the larger and more interconnected immune-naïve population has crossed a threshold resulting in more sustainable human-to-human transmission of MPXV. The current epidemic in the Western World is possibly a consequence of increased local transmission of MPXV in Africa. A new estimation of the basic and effective reproduction rate (R0 and Re) in different populations is required. National, regional, and international collaborations are needed to address research gaps related to MPX outbreaks.

Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant.

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Antimicrobial Resistance Patterns and Risk Factors Associated with Salmonella spp. Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross-Sectional Study.

The burden of antimicrobial use in agricultural settings is one of the greatest challenges facing global health and food security in the modern era. Malaysian poultry operations are a relevant but understudied component of epidemiology of antimicrobial resistance. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Salmonella isolates from poultry farms in three states of East Coast Peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) was collected from poultry operations. Characteristics of the sampled farms and associated risk factors were obtained using semi-structured questionnaires. Presumptive Salmonella spp. isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials using disk diffusion method. Our findings revealed that the proportion of Salmonella spp.-positive isolates across sample source were as following: cloacal swab (46.3%, 120/259); faecal (59.5%, 50/84); in tap water (14.3%, 2/14); and in sewage sample (35.7%, 5/14). Isolates from faecal (15.5%, 13/84), cloacal (1.2%, 3/259), and sewage (7.1%, 1/14) samples were significantly resistant to at least five classes of antimicrobials. Resistance to Sulfonamides class (52%, 92/177) was predominantly observed followed by tetracycline (39.5%, 70/177) and aminoglycosides (35.6%, 63/177). Multivariate regression analysis identified intensive management system (OR = 1.55, 95% CI = 1.00-2.40) as a leading driver of antimicrobial resistance (AMR) acquisition. A prevalence of resistance to common antimicrobials was recorded for sulfamethoxazole (33.9%), tetracycline (39.5%), and trimethoprim-sulphamethoxazole (37.9%). A close association between different risk factors and the prevalence of AMR of Salmonella strains suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the emergence and evolution of multidrug-resistant pathogen isolates. One Health approach is recommended to achieve a positive health outcome for all species.

Macrophage Migration Inhibitory Factor-An Innovative Indicator for Free Flap Ischemia after Microsurgical Reconstruction.

(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.

The niche of One Health approaches in Lassa fever surveillance and control.

Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa.

Identification of Risk Factors Associated with Resistant Escherichia coli Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross Sectional Study.

Antimicrobial resistance is of concern to global health security worldwide. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Escherichia coli (E. coli) resistance from poultry farms in Kelantan, Terengganu, and Pahang states of east coast peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) were collected. Characteristics of the sampled farms including management type, biosecurity, and history of disease were obtained using semi-structured questionnaire. Presumptive E. coli isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials and interpreted alongside risk factor data obtained from the surveys. We isolated 717 E. coli samples from poultry and environmental samples. Our findings revealed that cloacal (17.8%, 46/259), faecal (22.6%, 19/84), sewage (14.3%, 2/14) and tap water (7.1%, 1/14) were significantly (p < 0.003) resistant to at least three classes of antimicrobials. Resistance to tetracycline class were predominantly observed in faecal samples (69%, 58/84), followed by cloacal (64.1%, 166/259), sewage (35.7%, 5/14), and tap water (7.1%, 1/84), respectively. Sewage water (OR = 7.22, 95% CI = 0.95-151.21) had significant association with antimicrobial resistance (AMR) acquisition. Multivariate regression analysis identified that the risk factors including sewage samples (OR = 7.43, 95% CI = 0.96-156.87) and farm size are leading drivers of E. coli antimicrobial resistance in the participating states of east coast peninsular Malaysia. We observed that the resistance patterns of E. coli isolates against 12 panel antimicrobials are generally similar in all selected states of east coast peninsular Malaysia. The highest prevalence of resistance was recorded in tetracycline (91.2%), oxytetracycline (89.1%), sulfamethoxazole/trimethoprim (73.1%), doxycycline (63%), and sulfamethoxazole (63%). A close association between different risk factors and the high prevalence of antimicrobial-resistant E. coli strains reflects increased exposure to resistant bacteria and suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the future threat of emergence of multidrug-resistant pathogen isolates. Public health interventions to limit antimicrobial resistance need to be tailored to local poultry farm practices that affect bacterial transmission.

Association of smoking status with hospitalisation for COVID-19 compared with other respiratory viruses a year previous: a case-control study at a single UK National Health Service trust.

Background: It is unclear whether smoking increases the risk of COVID-19 hospitalisation. We first examined the association of smoking status with hospitalisation for COVID-19 compared with hospitalisation for other respiratory viral infections a year previous. Second, we examined the concordance between smoking status recorded on the electronic health record (EHR) and the contemporaneous medical notes. Methods: This case-control study enrolled adult patients (446 cases and 211 controls) at a single National Health Service trust in London, UK. The outcome variable was type of hospitalisation (COVID-19 vs. another respiratory virus a year previous). The exposure variable was smoking status (never/former/current smoker). Logistic regression analyses adjusted for age, sex, socioeconomic position and comorbidities were performed. The study protocol and analyses were pre-registered in April 2020 on the Open Science Framework. Results: Current smokers had lower odds of being hospitalised with COVID-19 compared with other respiratory viruses a year previous (OR adj=0.55, 95% CI=0.31-0.96,  p=.04). There was no significant association among former smokers (OR adj=1.08, 95% CI=0.72-1.65,  p=.70). Smoking status recorded on the EHR (compared with the contemporaneous medical notes) was incorrectly recorded for 168 (79.6%) controls (χ 2(3)=256.5,  p=<0.001) and 60 cases (13.5%) (χ 2(3)=34.2,  p=<0.001). Conclusions: In a single UK hospital trust, current smokers had reduced odds of being hospitalised with COVID-19 compared with other respiratory viruses a year previous, although it is unclear whether this association is causal. Targeted post-discharge recording of smoking status may account for the greater EHR-medical notes concordance observed in cases compared with controls.

The association of smoking status with SARS-CoV-2 infection, hospitalization and mortality from COVID-19: a living rapid evidence review with Bayesian meta-analyses (version 7).

AIMS: To estimate the association of smoking status with rates of (i) infection, (ii) hospitalization, (iii) disease severity and (iv) mortality from SARS-CoV-2/COVID-19 disease. DESIGN: Living rapid review of observational and experimental studies with random-effects hierarchical Bayesian meta-analyses. Published articles and pre-prints were identified via MEDLINE and medRxiv. SETTING: Community or hospital, no restrictions on location. PARTICIPANTS: Adults who received a SARS-CoV-2 test or a COVID-19 diagnosis. MEASUREMENTS: Outcomes were SARS-CoV-2 infection, hospitalization, disease severity and mortality stratified by smoking status. Study quality was assessed (i.e. 'good', 'fair' and 'poor'). FINDINGS: Version 7 (searches up to 25 August 2020) included 233 studies with 32 'good' and 'fair' quality studies included in meta-analyses. Fifty-seven studies (24.5%) reported current, former and never smoking status. Recorded smoking prevalence among people with COVID-19 was generally lower than national prevalence. Current compared with never smokers were at reduced risk of SARS-CoV-2 infection [relative risk (RR) = 0.74, 95% credible interval (CrI) = 0.58-0.93, τ = 0.41]. Data for former smokers were inconclusive (RR = 1.05, 95% CrI = 0.95-1.17, τ = 0.17), but favoured there being no important association (21% probability of RR ≥ 1.1). Former compared with never smokers were at somewhat increased risk of hospitalization (RR = 1.20, CrI = 1.03-1.44, τ = 0.17), greater disease severity (RR = 1.52, CrI = 1.13-2.07, τ = 0.29) and mortality (RR = 1.39, 95% CrI = 1.09-1.87, τ = 0.27). Data for current smokers were inconclusive (RR = 1.06, CrI = 0.82-1.35, τ = 0.27; RR = 1.25, CrI = 0.85-1.93, τ = 0.34; RR = 1.22, 95% CrI = 0.78-1.94, τ = 0.49, respectively), but favoured there being no important associations with hospitalization and mortality (35% and 70% probability of RR ≥ 1.1, respectively) and a small but important association with disease severity (79% probability of RR ≥ 1.1). CONCLUSIONS: Compared with never smokers, current smokers appear to be at reduced risk of SARS-CoV-2 infection, while former smokers appear to be at increased risk of hospitalization, increased disease severity and mortality from COVID-19. However, it is uncertain whether these associations are causal.