Importance of non-pharmaceutical interventions in lowering the viral inoculum to reduce susceptibility to infection by SARS-CoV-2 and potentially disease severity

Clinicians and researchers observing the natural history of endemic and epidemic infections have always been fascinated by the vagaries of these diseases, in terms of both the changing nature of the disease severity and phenotype over time and the variable susceptibility of hosts within exposed populations. SARS-CoV-2, the virus that causes COVID-19 and is believed to originate from bats, quickly transformed into a global pandemic. The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing great threats to the global health in many aspects. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Comprehensive understanding of the biology of SARS-CoV-2 and its interaction with hosts is fundamentally important in the fight against SARS-CoV-2. Advanced age, male sex, and comorbidities such as hypertension and cardiovascular disease as well as diabetes and obesity have been identified as risk factors for more severe COVID-19. However, which and to what extent specific genetic factors may account for the predisposition of individuals to develop severe disease or to contract the infection remains elusive. The increasing availability of data from COVID-19 patient populations is allowing for potential associations to be established between specific gene loci and disease severity, susceptibility to infection, and response to current/future drugs.

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Cardiovascular drugs and COVID-19 clinical outcomes: a living systematic review and meta-analysis

10.1101/2020.10.07.20208918 ◽

2020 ◽

Author(s):

Innocent G Asiimwe ◽

Sudeep Pushpakom ◽

Richard M Turner ◽

Ruwanthi Kolamunnage-Dona ◽

Andrea Jorgensen ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Disease Severity ◽

Meta Analysis ◽

Severe Disease ◽

Cardiovascular Drugs ◽

Susceptibility To Infection ◽

Drug Classes ◽

All Cause Mortality ◽

Length Of Hospitalization

ABSTRACTOBJECTIVETo continually evaluate the rapidly evolving evidence base on the role of cardiovascular drugs in COVID-19 clinical outcomes (susceptibility to infection, hospitalization, hospitalization length, disease severity, and all-cause mortality).DESIGNLiving systematic review and meta-analysis.DATA SOURCESEligible publications identified from >500 databases indexed through 31st July 2020 and additional studies from reference lists, with planned continual surveillance for at least two years.STUDY SELECTIONObservational and interventional studies that report on the association between cardiovascular drugs and COVID-19 clinical outcomes.DATA EXTRACTIONSingle-reviewer extraction and quality evaluation (using ROBINS-I), with half the records independently extracted and evaluated by a second reviewer.RESULTSOf 23,427 titles screened, 175 studies were included in the quantitative synthesis. The most reported drug classes were angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with ACEI/ARB exposure being associated with higher odds of testing positive for COVID-19 (pooled unadjusted OR 1.15, 95% CI 1.02 to 1.30). Among patients with COVID-19, unadjusted estimates showed that ACEI/ARB exposure was associated with being hospitalized (OR 2.25, 1.70 to 2.98) and having severe disease (OR 1.50, 1.27 to 1.77) but not with the length of hospitalization (mean difference −0.45, −1.33 to 0.43 days) or all-cause mortality (OR 1.25, CI 0.98 to 1.58). However, after adjustment, ACEI/ARB exposure was not associated with testing positive for COVID-19 (pooled adjusted OR 1.01, 0.93 to 1.10), being hospitalized (OR 1.16, 0.80 to 1.68), having severe disease (1.04, 0.76 to 1.42), or all-cause mortality (0.86, 0.64 to 1.15). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with being hospitalized (OR 0.84, 0.58 to 1.22), disease severity (OR 0.88, 0.68 to 1.14) or all-cause mortality (OR 0.77, 0.54 to 1.12) while it decreased the length of hospitalization (mean difference −0.71, −1.11 to −0.30 days). After adjusting for relevant covariates, other cardiovascular drug classes were mostly not found to be associated with poor COVID-19 clinical outcomes. However, the validity of these findings is limited by a high level of heterogeneity in terms of effect sizes and a serious risk of bias, mainly due to confounding in the included studies.CONCLUSIONOur comprehensive review shows that ACEI/ARB exposure is associated with COVID-19 outcomes such as susceptibility to infection, severity, and hospitalization in unadjusted analyses. However, after adjusting for potential confounding factors, this association is not evident. Patients on cardiovascular drugs should continue taking their medications as currently recommended. Higher quality evidence in the form of randomized controlled trials will be needed to determine any adverse or beneficial effects of cardiovascular drugs.PRIMARY FUNDING SOURCENoneSYSTEMATIC REVIEW REGISTRATIONPROSPERO (CRD42020191283)

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Biomarkers for susceptibility to infection and disease severity in human malaria

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02762011000900009 ◽

2011 ◽

Vol 106 (suppl 1) ◽

pp. 70-78 ◽

Cited By ~ 17

Author(s):

Bruno Bezerril Andrade ◽

Manoel Barral-Netto

Keyword(s):

Disease Severity ◽

Human Malaria ◽

Susceptibility To Infection

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Risk of Sars-CoV-2 infection and disease severity in people at socioeconomic disadvantage in Italy

European Journal of Public Health ◽

10.1093/eurpub/ckab164.552 ◽

2021 ◽

Vol 31 (Supplement_3) ◽

Author(s):

S Mazzilli ◽

A Chieti ◽

V Casigliani ◽

S Forni ◽

A Nannavecchia ◽

...

Keyword(s):

Disease Severity ◽

Socioeconomic Disadvantage ◽

Health Policies ◽

Socioeconomic Vulnerability ◽

Susceptibility To Infection ◽

Italian Regions ◽

Increased Risk ◽

Gender And Age ◽

The Relationship ◽

Regional Surveillance

Abstract Background Evidence accumulated in the past months indicating that COVID-19 affects people at socioeconomic (SE) disadvantage more strongly. This is embodied by the COVID-19 syndemic concept, i.e., the biological, economic, and social interactions between non-communicable diseases and COVID-19 increase a person's susceptibility to infection and worse health outcomes. Here, we explored the relationship among the SE position and the risk of Sars-CoV-2 infection and disease severity in Tuscany and Apulia, two Italian regions, during the 1st(Feb-Jun2020) and 2nd(Sep-Dec2020) epidemic waves. Methods We included all individuals tested (only for Apulia) and/or resulted positive for SARS-CoV2(for Tuscany and Apulia) and reported to regional surveillance system. We linked surveillance data with the deprivation index (DI)(1-5 scale; DI = 5 highest deprivation) of the area of living. We calculated the relative risk (RR) of acquiring Sars-CoV-2, COVID-19-related hospitalization, and death of deprived individuals compared with people in the highest SEP-we adjusted for gender and age. Results A total of 159507 (82897 F; 76610 M) individuals with prior or current Sars-CoV-2 infection were included in our study, 71320 from Apulia and 88187 from Tuscany. For people aged over 30, and with a DI > 2, the RR of acquiring the infection increased for individuals with higher DI. The RR of being hospitalized and of death, were significantly higher for people over 30 with DI = 5. In Apulia, test positivity rate was comparable across all population groups during the 1stwave, while it increased among individuals with higher DI during the 2ndwave. Conclusions According to our results, SE disadvantage is associated with an increased risk of acquiring Sars-CoV-2, and to suffer from severe outcomes when infected. Based on available data, diagnostic test access was more equitable during 1stepidemic wave. This study calls for targeted health policies and actions to protect those with the greatest SE vulnerability. Key messages Available Italian data, indicate that higher socioeconomic disadvantage is associated with an increased risk of acquiring Sars-CoV-2, and to suffer from severe outcomes when infected. Our study highlights the importance of adopting targeted health policies and action to protect those with the greatest socioeconomic vulnerability and enhance equity.

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Older leaf tissues in younger plants are more susceptible to soybean rust

Acta Scientiarum Agronomy ◽

10.4025/actasciagron.v39i1.30638 ◽

2017 ◽

Vol 39 (1) ◽

pp. 17 ◽

Cited By ~ 3

Author(s):

Sheila Ariana Xavier ◽

Daiane Cristina Martins ◽

Lucas Henrique Fantin ◽

Marcelo Giovanetti Canteri

Keyword(s):

Experimental Design ◽

Disease Severity ◽

Leaf Age ◽

Reproductive Stage ◽

Soybean Rust ◽

Soybean Plant ◽

Phenological Stage ◽

Susceptibility To Infection ◽

Leaf Tissues ◽

Soybean Leaf

The aim of this study was to clarify the relationship between soybean leaf/plant age and the susceptibility to infection by Phakopsora pachyrhizi. Two studies were conducted in the greenhouse during the 2009/2010 season using the BRS 232 cultivar. The experimental design for Study 1 was fully randomized in a 2 x 3 factorial arrangement (phenological stage x age of the 4th, 5th and 6th trifoliate at the time of inoculation), and in Study 2, the experimental design was fully randomized with five treatments (T) and four replicates. The variables assessed were disease severity, number of lesions, uredinia per lesion, and viable spores. In Study 1, it was observed that disease severity was lower when the plant was in the growth stage V6 (11.4%), compared to the reproductive stage R4 (16.9%). The regression for disease severity and leaf age at the time of inoculation showed that older trifoliates on the plants in the reproductive stage exhibited higher severity. However, in Study 2, for trifoliates of the same age on plants of different ages, the trifoliates of younger plants were more susceptible to the disease. It was concluded that soybean plant susceptibility to soybean rust was directly proportional to the age of the trifoliate on a given plant and the phenological stage of the plant at the time of inoculation.

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Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity

Human Genomics ◽

10.1186/s40246-020-00290-4 ◽

2020 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Cleo Anastassopoulou ◽

Zoi Gkizarioti ◽

George P. Patrinos ◽

Athanasios Tsakris

Keyword(s):

Disease Severity ◽

Genetic Factors ◽

Current Knowledge ◽

Wide Spectrum ◽

Clinical Manifestations ◽

Severe Pneumonia ◽

Cell Surface Receptor ◽

Main Body ◽

Susceptibility To Infection ◽

Novel Coronavirus

Abstract Background The emergence of the novel coronavirus in Wuhan, Hubei Province, China, in December 2019 marked the synchronization of the world to a peculiar clock that is counting infected cases and deaths instead of hours and minutes. The pandemic, highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has indeed caused considerable morbidity and mortality and drastically changed our everyday lives. As we continue to become acquainted with the seventh coronavirus known to infect our species, a number of its characteristics keep surprising us. Among those is the wide spectrum of clinical manifestations of the resulting coronavirus disease 2019 (COVID-19), which ranges from asymptomatic or mildly symptomatic infections to severe pneumonia, respiratory failure, and death. Main body Data, now from patient populations, are beginning to accumulate on human genetic factors that may contribute to the observed diversified disease severity. Therefore, we deemed it prudent to review the associations between specific human genetic variants and clinical disease severity or susceptibility to infection that have been reported in the literature to date (at the time of writing this article in early August 2020 with updates in mid-September). With this work, we hope (i) to assist the fast-paced biomedical research efforts to combat the virus by critically summarizing current knowledge on the potential role of host genetics, and (ii) to help guide current genetics and genomics research towards candidate gene variants that warrant further investigation in larger studies. We found that determinants of differing severity of COVID-19 predominantly include components of the immune response to the virus, while determinants of differing susceptibility to SARS-CoV-2 mostly entail genes related to the initial stages of infection (i.e., binding of the cell surface receptor and entry). Conclusion Elucidating the genetic determinants of COVID-19 severity and susceptibility to SARS-CoV-2 infection would allow for the stratification of individuals according to risk so that those at high risk would be prioritized for immunization, for example, if or when safe and effective vaccines are developed. Our enhanced understanding of the underlying biological mechanisms could also guide personalized therapeutics. Such knowledge is already beginning to provide clues that help explain, at least in part, current epidemiologic observations regarding the typically more severe or benign disease course in older males and children, respectively.

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Effects of mechanical thinning on botrytis bunch rot on Sauvignon blanc wine grapes

New Zealand Plant Protection ◽

10.30843/nzpp.2021.74.11729 ◽

2021 ◽

Vol 74 (1) ◽

pp. 30-36

Author(s):

Dion C. Mundy ◽

Michael C.T. Trought ◽

Andrew R.G. McLachlan ◽

Susan M. Neal ◽

Dominic Pecchenino

Keyword(s):

Botrytis Cinerea ◽

Disease Severity ◽

Disease Risk ◽

Cost Effective ◽

Sauvignon Blanc ◽

Susceptibility To Infection ◽

Mechanical Thinning ◽

Bunch Rot ◽

Disease Pressure ◽

Heavy Machine

Mechanical fruit thinning could be a practical and cost-effective alternative to hand thinning of Sauvignon blanc grapes to increase quality by reducing yield. Botrytis bunch rot, caused by the fungus Botrytis cinerea, is the main seasonal disease risk for grapes grown in New Zealand but it is unknown if this disease is exacerbated by mechanical rather than manual thinning of the vines. It was hypothesised that the damage caused by mechanical thinning would result in more disease or increase disease pressure than hand thinning or no thinning. Botrytis bunch rot was determined in the field at harvest following mechanical thinning in the 2009, 2010 and 2011 seasons compared with an un-thinned control. In the 2011 season, possible mechanisms that may have influenced disease severity were investigated. The parameters investigated were: bunch openness; berry susceptibility to infection; and percentage of bunch debris infected with Botrytis cinerea. Mechanical thinning resulted in the same or lower observed disease severity compared with the un-thinned control in the 2009, 2010 and 2011 seasons while reducing yield as desired. In all seasons, both heavy and light machine thinning treatments reduced incidence of botrytis compared to the un-thinned control and the heavy machine treatment always reduced disease severity compared to the un-thinned control. Berry susceptibility to Botrytis cinerea was a complex interaction between various factors. Heavy machine thinned berries without wounding and inoculation were significantly less susceptible than the un-thinned control. Further investigation will be required to determine if the significant differences observed in berry susceptibility to infection and total infected bunch debris per bunch can be correlated with observed field disease levels.

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