Background: Priming with ChAdOx1 followed by heterologous boosting have been considered in several countries. Nevertheless, analyses that provide a comparison of the immunogenicity of heterologous booster in comparison to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between heterologous prime-boost vaccination using BNT162b2 or mRNA-1273 and homologous primary vaccination regimens. Methods: We matched vaccinated naïve individuals (VN; n=673) who had received partial vaccination (n=64), primary vaccination (n=590), or primary series plus one mRNA vaccine heterologous booster (n=19) with individuals with a documented primary SARS-CoV-2 infection and no vaccination record (natural infection; NI cohort; n=206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. Results: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary-BNT162b2 or mRNA-1273 vaccination regimens (P<0.05), but also showed ~3 fold less anti-S1 IgA response compared to infection-induced immunity (P<0.001). Nevertheless, heterologous booster dose resulted in a significant boost of at least ~12 folds in the immune response. Furthermore, correlation analyses revealed that both, anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas, among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization (r > 0.90, P < 0.001). Conclusion: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity.

Background School-aged children and school reopening dates have important roles in community influenza transmission. Although many studies evaluated the impact of reactive closures during seasonal and pandemic influenza outbreaks on medically attended influenza in surrounding communities, few assess the impact of planned breaks (i.e., school holidays) which coincide with influenza seasons, while accounting for differences in seasonal peak timing. Here, we analyze the effects of winter and spring breaks on influenza risk in school-aged children, measured by student absenteeism due to influenza-like illness (a-ILI). Methods We compared a-ILI counts in the two-week periods before and after each winter and spring break over five consecutive years in a single school district. We introduced a “pseudo-break” of 9 days’ duration between winter and spring break each year when school was still in session to serve as a control. The same analysis was applied to each pseudo-break to support any findings of true impact. Results We found strong associations between winter and spring breaks and a reduction in influenza risk, with a nearly 50% reduction in a-ILI counts post-break compared to the period before break, and the greatest impact when break coincided with increased local influenza activity. Conclusions These findings suggest that brief breaks of in-person schooling, such as planned breaks lasting 9-16 calendar days, can effectively reduce influenza in schools and community spread. Additional analyses investigating the impact of well-timed shorter breaks on a-ILI may determine an optimal duration for brief school closures to effectively suppress community transmission of influenza.

At present, Corona virus disease 2019(COVID-19) has become a major concern all over the world and leads to huge medical pressure. Antibody-dependent enhancement (ADE) of viral infection has been researched extensively in many viruses. It is not yet clear whether SARS-CoV-2 infection causes ADE effects. However, there is evidence that ADE may be found in COVID-19. We have discussed the possibilities of ADE effect induced by COVID-19 and proposed a series of measures to deal with it.

Secondary pneumomediastinum in patients with ARDS is often related to invasive mechanical ventilation due to high airway pressures leading to alveolar rupture.1 The pathophysiologic mechanism through which this occurs is known as the Macklin effect which describes the idea that alveolar rupture causes a leakage of air along the bronchovascular bundle whereby it extends into the mediastinum.2 Another contributing factor to alveolar rupture is the diffuse alveolar damage seen in patients with severe ARDS.3   Here we present a case series from a major New York City academic hospital of 18 patients with Covid-19 complicated by pneumomediastinum in the setting of both invasive and noninvasive ventilation.             The data collected was obtained on April 19th during which 130 Covid-19 infected patients were intubated and in the intensive care unit since March 26th 2020. Four patients were excluded from analysis due to inability to exclude pneumomediastinum as a line-associated complication. All intubations were done by the most senior clinician available. The median age of the patients was 60 years and 55.6% were men. The most common comorbidities were hypertension (38.9%) and diabetes mellitus (33.3%). Most pneumomediastinum cases (83.3%) were in association with invasive mechanical ventilation and 46.7% occurred within the first day of intubation. An additional 40% of pneumomediastinum cases occurred between day 1 and day 6. Those intubated were placed on an average of 6.58 cc/kg of tidal volume. Only 20% of patients experienced peak inspiratory pressures greater than 35 mm Hg and 13.3% had plateau pressures greater than 30 mm Hg. High PEEP strategy defined as greater than 12 mm Hg was used in 40% of patients. The most frequent concurrent complications observed were subcutaneous emphysema (72.2%) and pneumothorax (55.6%). Figure 1 shows a single axial cut of a CT scan of the Chest of one patient who experienced severe subcutaneous emphysema, pneumomediastinum and diffuse bilateral lung infiltrates due to Covid-19. The in hospital mortality rate at the time of publication is 44.4%.             The prevalence of pneumomediastinum cases due to COVID-19 in this study was 13.8%. This is significantly more frequent than that observed with protective ventilation strategy which was as low as 7%.4 Interestingly, a previous study of SARS-Cov1 estimated a total incidence of 12% of patients with pneumomediastum.5             The large number of pneumomediastinum cases observed in this case series seems to be unexplained solely by barotrauma from mechanical ventilation in these patients treated with protective lung strategy and may be specific to the underlying pathology of Covid-19. Of note, three patients who developed this complication were receiving noninvasive ventilation further supporting this hypothesis.  Conflict of Interest: None  References:1.   Ioannidis G, Lazaridis G, Baka S, et al. Barotrauma and pneumothorax. J Thorac DIs. 2015;7(Suppl 1):S38-S43 2.   Jacobi A, Chung M, Bernheim A, Eber C. Portable chest X-ray in coronavirus disease-19 (COVID-19): A pictorial review. Clinical Imaging. 2020;64:35–42. 3. Murayama S. Spontaneous pneumomediastinum and Macklin effect: Overview and appearance on computed tomography. World Journal of Radiology. 2014;6(11):850.4. Passos Amato M, Valente Barbas C, Medeiros D, et al. Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. New England Journal of Medicine. 1998;338:347-3545. Peiris J, Chu C, Cheng V, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–72.

COVID-19 has now become a global epidemic, prevailing over 213 countries of the world including Pakistan. To date, there have been more than 12000 cases and above 220 deaths reported in Pakistan. The outbreak is caused by a β-coronavirus called SARS-CoV-2, similar in characteristics to the SARS and MERS-CoV. It shows symptoms like pneumonia and may lead to death. Despite lockdown and possible isolation system, it is spreading rapidly. Lack of precautionary measures, specific vaccine and delayed diagnosis may be the major reasons for its spread. Several researches on COVID-19 have described its various features to extend its knowledge in order to help the scientific world in preparation of vaccine. Current review aimed to cover all essential data such as clinical characteristics, pathology, detailed morphology and structure, antigenicity of COVID-19 virus, role of structural proteins in anti-viral drug development and possible treatments being used. This manuscript would be helpful to select the best possible treatment depending on the availability and condition of the patient. Moreover, further research is needed for assistance in designing a virus-specific drug or vaccine.

To the Editor,Is it worth wearing a face mask? That is the question many people ask during the COVID-19 pandemic. To better understand answers of individuals to this question and their subsequent risk, we first recall the prisoner’s dilemma, a classic example of Game Theory, and then apply the same ideas to the decision of wearing a face mask.In the prisoner’s dilemma, two individuals, A and B, are arrested and put in a solitary confinement being both suspected of a robbery.1 Each of the prisoners has a choice between either testifying that the other committed the crime, or remaining silent. The prosecutor comes with the following offer to each prisoner separately: if you testify and the other remains silent, you will be free and the other will be imprisoned for three years, and vice versa. However, if you both testify, you will both get two years of imprisonment. Finally, if you both remain silent, you get one year each. At the personal level, testifying that the other did it is more interesting than remaining silent: if the other prisoner remains silent, testifying will get you free; if he testifies, testifying will result in two years in prison instead of three. Therefore, the two prisoners will tend to testify against each other and will get two years of imprisonment each. Meanwhile, if they had both cooperated and remained silent, they would both have ended up in a better situation as they would have been sentenced to one year of imprisonment instead of two.Consider now a group of N +1 individuals among whom contact patterns and disease transmission are the same in a situation where there is sustained human-to-human infection. Here, we are looking at the consequences of getting infected (P) if an individual i decides to wear a mask or not, and the effort (E) needed to get and wear the mask. Let C0 be the risk of i getting infected when all other N individuals wear a mask, and δ1, δ2, …, δN , the additional risk of getting infected when 1, 2, …, N subjects don’t wear a mask. Denote the percentage of protection obtained when wearing a mask by ε. The probability of i being infected and the effort needed when deciding to wear a mask or not, can be formulated as shown in Table 1.When, for example, r individuals do not wear a mask, if idecides to wear a mask, the effort f needed for this decision results in a decreased risk of infection is (C0+δ r)ε . Weighing this gain against the effort helps in choosing whether to wear a mask or not.At the individual level, i may well be tempted not to wear a mask: for non-surgical masks the gain (C0+δ r)ε can be low, as the level of protection can be small against submicron particles.2 In addition, if improperly manipulated, masks may even increase the risk of contamination.3 Finally, COVID-19 infection was reported to also happen via the eyes which are not covered by the mask.4 All this while a substantial effortf may be needed to be able to manage the discomfort and proper handling of the mask.However, if all the other individuals, reasoning like i , also decide not to wear masks the resulting risk of getting infected becomes C0 + δN . This would mean an increase of C0 ε + δN in infection risk compared to the situation where everyone wore a mask. The addition of δN to the reduction in infection risk can justify wearing a mask as δN is likely to be nonnegligible: if everybody, including the infected ones who are asymptomatic, but infectious, were wearing a mask, this could significantly reduce the virus transmission.5,6,7 In fact, the indirect protective effect of everybody else wearing a mask on decreasing the infection risk δN may be much higher than the direct protective effect (C0+δ r)ε of wearing a mask.Other factors may influence the decision of whether to wear or not a mask, but it is unlikely that the protective aspects and the burden linked to their use would not play significant roles in the decision of wearing them. Given a potentially weak protective effect, a significant effort needed to wear them, and a marked disease containment indirect effect, we may well end up in a prisoner’s dilemma situation. The question is then how to bring the individuals to cooperate and reach the optimal situation of wearing masks. Several options can be considered, spanning from simple encouragement to enforcement. Educating the public by explaining the benefit of everybody wearing even imperfectly sealed masks could provide a potentially cheap and effective measure.8Another option could be to lower the effort f by making good quality and easy to use masks widely available. These initiatives along with other incentives to foster a cooperative behaviour amongst individuals could be key to achieve widespread use of masks to fight against the COVID-19 pandemic, especially when easing lockdown restrictions.DisclaimerEmmanuel Aris is currently employed by GSK, but wrote this article in his personal capacity. The views expressed are his own and do not necessarily represent the views of GSK.References1. Nash J. Non Cooperative Games. Annals of Mathematics  1951;54: 286–295. DOI: 10.2307/1969529.2. Rengasamy S, Eimer B, Shaffer RE. Simple Respiratory Protection—Evaluation of the Filtration Performance of Cloth Masks and Common Fabric Materials Against 20–1000 nm Size Particles. Ann. Occup. Hyg. 2010; 54:789–798. DOI: 10.1093/annhyg/meq044. Epub 2010 Jun 28.3. World Health Organization. Advice on the use of masks in the community setting in Influenza A (H1N1) outbreaks. Interim guidance (3 May 2009). http://www.who.int/csr/resources/publications/Adviceusemaskscommunityrevised.pdf Date: 2020. Accessed April 20th 2020.4. Li JPO, Lam DSC, Chen Y, et al . Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. Br J Ophthalmol 2020;104: 297-298. DOI:10.1136/bjophthalmol-2020-315994.5. Yu X, Yang R. COVID-19 transmission through asymptomatic carriers is a challenge to containment. Influenza Other Respi Viruses . 2020;00:1–2.6. Feng S, Shen C, Xia, N, et al . Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med 2020 https://doi.org/10.1016/ S2213-2600(20)30134-X.7. Johnson DF, Druce JD, Birch C, Grayson ML. A Quantitative Assessment of the Efficacy of Surgical and N95 Masks to Filter Influenza Virus in Patients with Acute Influenza Infection. Clinical Infectious Diseases 2009; 49: 275–277 DOI: 10.1086/600041.8. Greenhalgh T, Schmid, MB, Czypionka T, et al. Face masks for the public during the covid-19 crisis. BMJ , 2020;369:m1435 DOI: https://doi.org/10.1136/bmj.m1435.

The novel coronavirus outbreak arose in Wuhan, China in Dec, 2019. It is declared the 6th public health emergency by the WHO and named as COVID-19. SARS-CoV-2 is non-segmented positive sense ssRNA virus, belongs to the Coronaviridae under the Nidovirales and spread largely in human being and other mammals. Person to person, airborne and surface transmission is common, the virus get entered to host through nose, mouth, eyes, food, water and feces. An infected patients can transmit the virus to 2.2 healthy individuals. A patient in the US showed gastrointestinal symptoms vomiting, nausea and pass loose stools. Later the patient declared positive for SARS-CoV-2 on the basis of viral detection in stools and respiratory samples. The gastrointestinal symptoms like diarrhea, nausea, vomiting, abdominal discomfort and detection of SARS-CoV-2 in stools of infected and recovered patients indicates potential oral-fecal transmission route, it could be potential risk for the spread of COVID-19. The flatus is gas produced by aerophagia or bacterial fermentation in intestine and expelled out through esophagus or anus. It consists of Hydrogen, Oxygen, Nitrogen, Carbon dioxide and Methane, their percentage composition is 99%. Previous study showed that bacteria can transmit through bare-bottom farting. The gastrointestinal manifestation and possible oral-fecal transmission, the flatulence could be the risk of transmission for COVID-19. Personal hygiene must be adapted to prevent the spread of disease.