Dengue fever is a viral fever due to the dengue virus (DENV) which affects many tropical and subtropical countries across the globe and has resulted in significant mortality and morbidity. Recently it has been noted that dengue has spread to certain countries in Europe due to air travel and climate change. Clinically dengue can present with mild flu-like symptoms, but can also progress to severe dengue which may lead to organ impairment and death. Treatment is mostly symptomatic and prevention has been focused on mosquito control. Immune response against dengue is complex in such a way that it protects but may also promote the infection in certain instances. Antibody dependent enhancement has been a significant challenge in vaccine development as antibodies against dengue promote disease against heterologous serotypes. The lack of an animal model has also made vaccine research challenging. Dengvaxia, a dengue vaccine for seropositive individuals between the ages of 9-45 has been licensed despite the significant challenges. Several other vaccine candidates are also in different stages of clinical trials in the hopes of preventing dengue in all age groups without any adverse effects. Knowledge regarding dengue vaccines and its effects on the di­sease is continuously evolving. Clinical data gained from trials should be made available to regulatory bodies to ensure the best decision is made on how to utilise vaccination to best prevent the spread of dengue.

The current coronavirus disease 19 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and its variants. Though various vaccines are now available in the market and become effective in reducing the severity of disease and hospitalization, still for those who are infected with SARS-CoV-2 there is no effective treatment to deal with this health emergency, and therefore, there is an urgent need for the new treatments. The design of new therapies must be focused not only on the elimination of the virus but also on the recovery of the affected lung tissue and the avoidance or reduction of the severe sequels. In that sense, treatments based on regenerative medicine and specifically platelet-rich plasma (PRP) could be found suitable and effective to tackle this disease. Lyophilized PRP in nebulized form can be effective as it directly enters the lungs and unique properties of PRP such as immunomodulatory, anti-inflammatory, angiogenic, anti-fibrotic and anti-apoptotic, anti-bacterial properties as well as stimulation of different cells, etc. exerts their effect to improve the health condition rapidly.  However, further studies are warranted to prove its efficacy. In this review, we used words like COVID-19, drugs used in the nebulized form in COVID-19, platelets, the role of platelets in various disease conditions, platelet-rich plasma, nebulization, lyophilization for selecting, extracting, and synthesizing data using Google search engine, PubMed search. This review is focused on the advantages and applications of LPRP in nebulized form as a treatment in COVID-19 patients.

Hyperkalemia develops in about 10% of outpatients within one year after angiotensin-converting enzyme (ACE) and angiotensin receptor blockers (ARB) drugs are prescribed. This study includes reviewing the pathophysiology of how these agents affect potassium levels within the body, risk factors for developing hyperkalemia, clinical signs and symptoms, and treatment to the patient having hyperkalemia. Important considerations before starting ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a serum potassium concentration, and also as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs which will also increase serum potassium. Elderly patients and those having chronic kidney disease are at greater risk of hyperkalemia. Before starting the therapy obtaining the glomerular filtration rate, baseline blood volumes of potassium, as well as whether the patient taking excessive potassium from diet, supplements, or drugs that can also increases the potassium concentration in the body. Understanding the mechanism of ACEi and ARBs coupled with rational use of drugs can minimize the risk of developing hyperkalemia.

With interest we read the article by Tutar et al. about a 76 years old male who developed fatigue, myalgia, and mild fever immediately after the second dose of the Sinovac vaccine, which lasted for a few days and progressive quadruparesis starting five days after the vaccination [1]. Based upon the clinical presentation and nerve conduction studies (NCSs), the patient was diagnosed with Guillain-Barre syndrome (GBS) subtype acute, motor and sensory, axonal neuropathy (AMSAN) and treated with intravenous immunoglobulins (IVIGs), which resulted in almost complete recovery of the clinical abnormalities  [1]. The study is appealing but raises the following comments and concerns. 

There is a discrepancy regarding the onset of quadruparesis. In the first sentence of the case description the authors state that the patient presented with quadruparesis since nine days but in the third sentence of the case description they state that progressive quadruparesis started 8 days after the vaccination.  Since he received the vaccination 14 days prior to presentation, suggesting that quadruparesis started 6 days prior to presentation [1]. This obvious inconsistency should be clarified.

A second discrepancy refers to the sensory abnormalities. In the first paragraph of the case presentation the authors mention that the patient complained about  progressive, ascending paresthesias in the lower limbs [1].  In the second paragraph of the case presentation they state that the patient had no sensory disturbances. The authors should clarify this inconsistency. 

A third discrepancy concerns the absence of abnormal spontaneous activity on needle electromyography (EMG). Since the patient was diagnosed with an axonal lesion, one would expect that the affected muscles are denervated which usually shows up on EMG as spontaneous activity. Absence of spontaneous activity in the presence of an axonal lesion should be clarified.

A limitation of the study is that no reference limits of the blood chemical values were provided [1], which prohibits assessing which value was inside or outside the normal range. Applying our own reference limits, the patient had an elevated D-dimer [1]. We should be told if this was due to the infection, due to deep venous thrombosis, due to pulmonary embolism, or due to venous sinus thrombosis.

A further limitation of the study is that the patient was diagnosed with AMSAN without application of the Brighton criteria. GBS is usually diagnosed according to the Brighton criteria, which requires not only a clinical exam and NCSs but also cerebro-spinal fluid (CSF) investigations, to assess if there was a dissociation cyto-albuminique or not. 

We do not agree that only two patients with SARS-CoV-2 vaccination related GBS in addition to the index case have been reported. In a recent review about the prevalence of SARS-CoV-2 vaccination related GBS, 19 patients with post-vaccination GBS were identified when collecting data as per the end of July 2021 [Finsterer, submitted]. 

Overall, the elegant study has several limitations which challenge the results and their interpretation. These objections should be met to reassess the data and thus strengthen the conclusions.

With interest we read the article by Zhang et al. about molecular, functional, and genetic investigations in 42 Han Chinese patients with Leber’s hereditary optic neuropathy (LHON) due to the primary LHON mutation m.3460G>A in MT-ND1 [1]. It was found that the variant impairs assembly of complex-I, reduces ATP production, decreases the mitochondrial membrane potential, increases ROS production in mutant cybrids, mediates apoptosis, and impairs mitophagy [1].  The study is appealing but has several limitations which raise the following comments and concerns.

Though LHON is commonly a disorder affecting retinal ganglion cells (RGCs) and the optic nerve [2], there is increasing evidence that any of the primary LHON mutations can also manifest in tissues other than the RGCs (LHON plus). Patients with LHON plus may additionally manifest with central nervous system (CNS) disease (dystonia, myoclonic epilepsy, temporal lobe epilepsy, leukoencephalopathy mimicking multiple sclerosis, psychomotor regression, posterior reversible encephalopathy syndrome (PRES), migraine with or without aura, chorea, cerebellar ataxia, dementia, or spinal cord problems), otologic disease (hypoacusis or hearing loss), endocrinological abnormalities (diabetes, pituitary adenoma, Hashimoto hypothyroidism, or hyperthyroidism), cardiac disease (dilated cardiomyopathy, ventricular arrhythmias, left ventricular hypertrabeculation, syncope, palpitations, angina, exertional dyspnoea, sudden cardiac death), vascular disease (aortic stiffness), bone marrow disease (anemia, fibrous dysplasia), kidney disease (renal failure), or peripheral nervous system (PNS)  disease (neuropathy, myopathy) [3]. In the eyes LHON patients may develop glaucoma or cataract in addition to RGC impairment [3]. Since these additional manifestations may be subclinical particular in the early stages of the disease, treating physicians have to actively look for them by prospective investigations. Since these manifestations can develop with progression of the disease, these investigations have to be regularly repeated during follow-up.

The standard treatment of LHON is idebenone (900mg/d) [4]. Idebenone has anti-oxidative capacities and is usually given at onset of the disease. Since idebenone may modify the phenotype and mitochondrial functions, we should be told how many of the 42 included patients were regularly taking idebenone and how many of them benefited from the drug. It should be additionally mentioned which other drugs the 42 included patients were regularly taking.

Though LHON mutations usually occur in the homoplasmic state [2], there are cases with heteroplasmic LHON mutations [5]. Since heteroplasmy rates not only influence the phenotypic expression but are crucial for genetic counselling [6], it is crucial that heteroplasmy rates of the m.3460G>A are presented. 

Overall, the study is appealing as it documents functional mitochondrial impairment in m.3460G>A carriers but has some limitations which should be addressed before drawing final conclusions.

With interest we read the article by Keddie et al. about the prevalence of Guillain-Barre syndrome (GBS) in Great Britain between January and May 2020 (retrospective, epidemiological part) and between March and May 2020 collecting data from 81 centers all over Britain (prospective part) [1]. It was concluded that neither the epidemiological nor the prospective cohort study supports a causal link between COVID-19 and GBS [1]. The study is appealing but raises concerns and comments.

Though there are indications that SARS-CoV-2 infections can be complicated by GBS [2], the index study found that the prevalence of GBS has not increased during the period January to May 2020 [1]. This obvious contradiction may be due to several reasons. First, it may be due to unawareness of the association between COVID-19 and GBS. Though GBS may be diagnosed correctly, the causal relation with COVID-19 may go unrecognised due to a long interval between onset of COVID-19 and onset of GBS, or due to only mild or asymptomatic COVID-19 infection. If patients with GBS in the absence of classical symptoms of COVID-19 do not undergo PCR or antibody tests, the viral infection may go unrecognised as the trigger of the neuro-immunologic compromise. 2. Work-up for GBS and diagnosed criteria applied may not be standardised for all participating centers. If the diagnostic criteria are not the same for all participating centers, there may be a number of false positive and false negative cases. If the false negatives outweigh the false positives, GBS may remain underdiagnosed. 3. Those not receiving intravenous immunoglobulins (IVIGs) may not show up in specific databases, why the number of GBS patients may be underestimated as well. 4. mild cases of GBS may go unrecognised because of restricted access to hospitals or ambulatory units during the pandemic. 5. SARS-CoV-2 associated GBS may remain undiagnosed in patients with severe COVID-19 being sedated and mechanically ventilated on an intensive care unit (ICU). If a patient is immobilised, muscle weakness may remain undetected and work-up for GBS may not be initiated. 6. The Brighton criteria for diagnosing GBS are applicable to GBS subtypes acute, inflammatory, demyelinating neuropathy (AIDP), acute, motor, axonal neuropathy (AMAN), and acute, motor and sensory, axonal neuropathy (AMSAN). These criteria, however, are not applicable to GBS subtypes Miller-Fisher syndrome (MFS), mono- or polyneuritis cranialis (PNC), the pharyngeal, cervical, and brachial (PCB) variant, and to Bickerstaff encephalitis (BFE). If patients with GBS more frequently develop subtypes not covered by the Brighton criteria, they may go undiagnosed, why the prevalence of SARS-CoV-2 associated GBS may remain low.

Arguments for a causal relation between SARS-CoV-2 and GBS are the increasing number of publications about patients developing GBS within a certain timeframe after onset of COVID-19 [2], the increasing number of publications about patients who develop GBS after SARS-CoV-2 vaccinations and cerebro-spinal fluid (CSF) studies demonstrating increased levels of cytokines in patients with SARS-CoV-2 associated CNS disease [3]. Arguments against a causal relation are that no epitope homology has been yet established and that the onset of GBS can precede that of COVID-19. 

COVID-19 is not only associated with headache, anosmia, dysgeusia, stroke, meningo-encephalitis, acute disseminated encephalo-myelitis (ADEM) and GBS, but with a much wider spectrum of neurological disease. This includes   cerebellitis,  acute,   hemorrhaghic, necrotising encephalitis (AHNE), myoclonus syndrome, limbic encephalitis, posterior reversible encephalopathy syndrome (PRES), intracerebral bleeding, subarachnoid bleeding, venous sinus thrombosis, transverse myelitis, cerebral vasculitis, cerebral vasoconstriction syndrome, epilepsy, psychosis, delirium, insomnia, carotid artery dissection, mono- and polyneuritis cranialis, myositis/dermatomyositis, and myasthenia [4]. Additionally, damage of the central and peripheral nervous system (CNS/PNS) due to anti-COVID-19 therapy should be considered.

A limitation of the study is that probable COVID-19 cases were included. Without confirmation of the infection by documentation of virus RNA or antibodies against the virus, SARS-CoV-2 associated GBS should not be diagnosed. 

A further limitation is that the prevalence of GBS was calculated upon data from an IVIG registry (NHSE immunoglobulin database) [1]. Since this database did include Scotland and since IVIGs may be given in indications other than GBS, figures deriving from this registry may be unreliable. 

According to the method section only patients developing GBS within 6 weeks after onset of COVID-19 were included [1]. However, in the results section a time interval between onset of COVID-19 and onset of GBS of 52 days in probable COVID-19 cases is mentioned [1]. This discrepancy should be clarified. 

Overall, the study has several limitations which challenge the results and their interpretation. Considering causes for underestimation of the true prevalence, the number of SARS-CoV-2 associated GBS cases is most probably higher than calculated. Particularly mild GBS cases, GBS subtypes not fulfilling the Brighton criteria, and cases with severe COVID-19 and GBS requiring mechanical ventilation may go unrecognised.

Honey is being increasingly used by experts in some part of the world on different wounds that are affected with multidrug resistant organism. Honey is believed to be nature’s antimicrobial agent that does not have resistance. Often, this honey has to be sterilized so that it is rendered as medical grade honey ready to be used on wounds. Gamma irradiation is the best method of sterilization with 15kGy dose being effective for honey sterilization as seen in our previous study. We conducted this study and observed that honey is sterile even after 18 months of irradiation and it can be continued to be used on wounds. To best of our knowledge, this is one of the first such observational studies on long term maintenance of honey sterility.

A new strain of coronaviruses that infects pigs has reappeared after its disappearance in 2017. The problem is that the Swine Acute Diarrhea Syndrome Coronavirus (SADS-CoV) may be transmitted from swine to humans. As a result of a recent study, it showed that the SADS-CoV can infect human cells with the same severity as animal cells. This may raise the alarm for the possibility of a new epidemic outbreak if the necessary precautions are not taken.