COVID‐19: vaccination problems Brüssow, Harald
Environmental microbiology,
June 2021, Letnik:
23, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
This minireview addresses problems of financing the vaccine development, regulatory questions, the ethics and efficacy of vaccine prioritization strategies and the coverage of variant viruses ...by current vaccines. Serious adverse effects observed with adenovirus vectored vaccines and mRNA vaccines in mass vaccination campaigns are reported. The ethical problems of continuing with placebo controlled vaccine trials and alternative clinical trial protocols are discussed as well as concrete vaccination issues such as the splitting of doses, the delaying of the second dose, the immunization with two different vaccine types and the need of vaccinating seropositive subjects. Strategies to increase vaccine acceptance in the population are shortly mentioned.
Summary
The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical ...interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning ‘dysbiosis’ that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case–control studies are underpowered necessitating more meta‐analyses that sort out consistent from spurious dysbiosis–disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe–microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.
Microbiome research has with the exception of fecal transplantation not yet reached the level of industrial applications with respect to gut microbiome engineering. Part of the difficulty might be the\complexity of the system, but some problems might reflect imprecise definitions like that for dysbiosis. Refutations of concepts should be part of the scientific process.
Immunology of COVID‐19 Brüssow, Harald
Environmental microbiology,
December 2020, Letnik:
22, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Summary
The immune response to SARS‐CoV‐2 reveals a delicate balance between protective effects and harmful pathological reactions and can possibly explain the highly variable disease manifestations ...in subjects infected with this novel coronavirus. A better understanding of the anti‐viral immune response is not only critical for vaccine development but might also provide targets for pharmaceutical and immunological treatment options. Recent research literature on immune aspects of COVID‐19 is summarized in this review with an outlook how bats have evolved to live with these viral infections.
Summary
Vaccines and drugs are the cornerstones in the fight against the SARS‐CoV‐2 pandemic. While vaccines were a success story, the development of antiviral drugs against SARS‐CoV‐2 turned out to ...be difficult. For an accelerated use of antivirals in the clinic, most SARS‐CoV‐2 antivirals represented repurposed drugs. The present article summarizes the outcomes of clinical trials with antiviral drugs in COVID‐19 patients. Many antiviral drugs failed to demonstrate beneficial effects or showed mixed results. One reason for the low success rate of clinical trials was shortcomings of antiviral tests in cell culture systems and another reason was the abundance of ill‐coordinated and underpowered clinical trials. However, large pragmatic clinical trials particularly of the British RECOVERY trial series demonstrated that even under emergency situation drug trials can be conducted in a timely way such that the therapy of COVID‐19 patients can be based on evidence basis instead on expert opinion or even worse on political pressure.
Summary
Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different ...continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.
Summary
Truth is threatened in our societies and one might wish that scientists should stand up for truth, but in order to do so, one needs to know what is truth and how it can be recognized. The ...oldest and most widely accepted concept of truth is the Correspondence Theory requesting a fit of propositions and reality. In the Coherence Theory truth is a consistent property of a whole system of propositions. In the Pragmatic Theory truth works in practical terms. Scientists have defined criteria to verify true statements by experiments and by the simplicity of theories. Aristotle proposed parsimony claiming the superiority of theories which derive from fewer hypotheses. David Hume suggested probability arguments to assess the force of evidence. Nicolai Hartmann elaborated a model based on the congruence of a priori logical arguments with a posteriori empirical observations. Karl Popper introduced the falsification of testable theories as a way to better theories. The analysis shows that scientific and medical research uses classical philosophical criteria of truth in their daily work. Humanities use different, hermeneutic criteria of truth. Finally, societies need for their coherence a dialectic approach to truth based on honest discussion of opposing views.
Summary
After reviewing antiviral drugs (Brüssow Environmental Microbiology 2021) the present review summarizes the results of clinical trials with host‐modifying drugs in COVID‐19 patients. Clinical ...benefits were observed with different immunomodulators. The variable outcomes of trials with the interleukin 6 receptor inhibitor tocilizumab demonstrated that treatment benefits might only be present in specific subgroups of patients or in specific infection stages. A meta‐analysis of trials with the interleukin 1 receptor antagonist anakinra showed a survival benefit only in patients with hyperinflammation. The Janus kinase inhibitor baricitinib is an anti‐inflammatory treatment that showed a clinical benefit in hospitalized patients who do not yet need supplementary oxygen. In contrast, the corticosteroid dexamethasone showed mortality reducing effects that were limited to patients on ventilation or in need of supplementary oxygen. Therapeutic dose of anticoagulation met the criteria for inferiority in severe cases, but showed a small survival benefit in non‐severe COVID‐19 patients. Large trials with colchicine showed a small or no survival benefit. Azithromycin, an antibiotic with immunomodulatory activity, showed no effects in numerous clinical trials. The trials showed a clear need for new drugs instead of repurposed drugs and drugs that specifically target the SARS‐CoV‐2 virus or the pathology developing in COVID‐19 patients.
Summary
The COVID‐19 pandemic is going into its third year with Europe again being the focus of major epidemic activity. The present review tries to answer the question whether one can come to grip ...with the pandemic by a combination of vaccinations and non‐pharmaceutical interventions (NPIs). Several COVID‐19 vaccines are of remarkable efficacy and achieve high protection rates against symptomatic disease, especially severe disease, but mathematical models suggest that the current vaccination coverage in many countries is insufficient to achieve pandemic control. NPIs are needed as complementary measures because recent research has also revealed the limits of vaccination alone. Here, we review the evidence for efficacy of face mask wearing in various settings. Overall pooled analysis showed significant reduction in COVID‐19 incidence with mask wearing, although heterogeneity between studies was substantial. Controlled trials of mask wearing are difficult to conduct, separating mask wearing effects in population studies from the impact of other NPIs is challenging and the efficacy of masks depend on mask material and mask fit. The combination of vaccination and mask wearing is potentially synergistic since vaccination protects so far well from disease development (the omicron variant is currently an unknown) but immunity from infection wanes over few months after vaccination. In comparison, masks interfere with the virus transmission process at a level of a physical barrier independent of coronavirus variant. Vaccination and masks are much less costly to apply than other NPI measures which are associated with high economic and social costs, but paradoxically both measures are the target of a vocal opposition by a sizable minority of the society. In parallel with biomedical research, we need more social science research into this opposition to guide political decisions on how to end the pandemic.
The present review tries to answer the question whether one can control the pandemic by a combination of vaccinations and non‐pharmaceutical interventions. The combination of vaccination and mask wearing is potentially synergistic since vaccination protects so far well from disease while masks interfere with the virus transmission process as a physical barrier against any type of coronavirus variant.
Summary
During the COVID‐19 pandemic, governments face difficult decisions when being confronted with public health threats and economic needs. Decision making is further complicated by the different ...perception of the pandemic by the public. Politicians as well as the public need objective facts for guidance and numbers play here a crucial role. The current contribution compiles numbers for infections, cases and deaths with SARS‐CoV‐2 to serve as an orientation help.
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