All HCWs who took at least two nasopharyngeal swabs for COVID-19 testing at two different time intervals during the study period were included. Throughout the mass testing period, various strategies such as practices of the new norm, daily temperature and symptom checking, wearing of appropriate personal protective equipment (PPE), identification of high-risk areas and travel declaration of staffs were within the hospital for prevention of COVID-19 transmission. We observed a small percentage of COVID-19 infected HCWs  from the mass testing. Both symptomatic and asymptomatic COVID-19 HCWs were almost equal in number. A majority of those infected were nurses  who had contact exposure to COVID-19 positive person or person under investigation (PUI) . Four of the COVID-19 infected HCWs  had no contact exposure. These HCWs were not identified through contact tracing. Fortunately, they were detected during the mass testing and were isolated promptly. In conclusion, mass testing of HCWs helped in early identification of COVID-19 infected HCWs not identified through contact tracing. Strategies such as stratified mass testing, strict compliance to new norm, appropriate PPE usage and identification of high-risk area were effective in the prevention of COVID-19 infection among HCWs.Approximately 1.29 million COVID-19 cases involving healthcare workers (HCWs) have been reported globally, leading to several hospitals conducting mass testing for early detection of infected HCWs. This study was conducted to report our experience and findings from the mass testing of HCWs from a public hospital in Sabah, Malaysia. The mass testing was conducted from 1 Descriptive analysis was performed and reported by median and interquartile range for continuous variables; frequency and percentage for categorical variables.p-value ≤0.25 were included in the full model. The full model was analysed using backward and forward stepwise Likelihood Ratio test; variables that were not significant were omitted from the full model. A p-value of ≤0.05 was considered statistically significant. A line chart was plotted using number of daily COVID-19 cases in Sabah, number of daily swabs and number of new cases of COVID-19 among HCWs from the public hospital from 1st March 2020 to 30th June 2020 for comparison of trend over time.Inferential analysis was done using multivariate logistic regression analysis, with the results of a positive COVID-19 RT-PCR test as the outcome variable. A pre-selection was performed using univariate logistic regression. Independent variables with The COVID-19 mass testing was facilitated by HCWs from the emergency department. Only trained doctors were allowed to take the swab specimens. Swab specimens were taken according to the Malaysian Ministry of Health guideline . All facThe HCWs were divided into two groups—exposed and non-exposed group. The exposed group were HCWs who had contact exposure with a COVID-19 infected person and were identified through contact tracing. Once identified, they were given the directive to immediately self-quarantine. Their first swab was taken on the 3rd day of contact exposure or immediately if the contact exposure had surpassed 3 days duration. They took the test on a walk-in basis. The non-exposed group were HCWs who had no contact exposure to COVID-19 infected person. This test was done on a scheduled basis. The appointment date was supervised by a senior colleague or a head of department to ensure that HCWs from the same department were tested in rotation. This was done to ensure that an adequate workforce was available at each department. All HCWs were required to self-quarantine after each swab. The turnover time for RT-PCR test was approximately 48 hours.The HCWs were informed of the RT-PCR test results through a phone call. If the first RT-PCR test was negative, a second swab test would be arranged 48 hours after their first swab test. HCWs from the non-exposed group with two negative results and who were asymptomatic were allowed to return to their duties once they were notified by the Occupational Safety and Health Administration (OSHA) officer. However, if they remained symptomatic, a 14 days quarantine needed to be completed before they could resume work. For HCWs from the exposed-group with two negative swab tests, a 14 days quarantine must be completed before they resumed work regardless of whether they were symptomatic or asymptomatic. If the RT-PCR test was positive, the HCW would be contacted and admitted immediately to a COVID-19 treatment hospital until they tested negative or were no longer infectious.To avoid a shortage in the PPE supply, the level of PPE used was in accordance with the COVID-19 Management Guideline from the Ministry of Health . A higheTemperature scan and check-in using the MySejahtera mobile application was made compulsory for all individuals entering the hospital compound. No visitor was allowed into the COVID-19 wards. For non-COVID-19 ward, only one caretaker with confirmed negative test for COVID-19 was allowed to be in the ward with the patient.All HCWs were reminded to practice physical distancing of at least 1-meter, proper hand hygiene and avoid crowded, closed or confined areas. Awareness was promoted rigorously through daily announcements via the public address system and infographic flyers. Hand sanitizers were allocated throughout the hospital including corridors for easy access. Smart paddle sanitizers were also introduced to reduce the risk of virus transmission through touch. Those caught violating the practices would be sternly warned and repeat offenders were compounded.Physical meetings were converted to virtual meetings and dine-in at cafeteria was prohibited; only take-away was allowed. For non-clinical HCWs, they were allowed to work from home; as for clinical HCWs, they worked in rotation or bubbles to reduce the physical interaction between HCWs. All HCWs needed to notify their Head of Department and OSHA officer if they displayed any symptoms of fever with influenza-like illness (ILI) or Severe Acute Respiratory Infection (SARI).Hospital pantries were identified as high-risk area in view of direct exposure between HCWs during meal time. Furthermore, the number of pantries was limited, and the pantry area was small and poorly ventilated. Therefore, the pantry usage was limited to two persons at a time for a duration of ten minutes. Acrylic dividers were also placed on the table to act as barrier between the people dining at the same table. The ward counters were also identified as a high-risk area. These places were constantly monitored to prevent over-crowding.The hospital implemented a compulsory COVID-19 RT-PCR test for all new staff. They had to have two negative results before they were allowed to begin their service. Another additional measure taken was the introduction of a travel declaration form where all HCWs needed to declare all inter-district and inter-state travel to the OSHA officer. Once they returned from their travel, they would be screened and notified by the OSHA officer if they needed to be tested again before they resumed work.st March 2020 to 30th June 2020. There were 2089 (91.86%) HCWs included in this study, 78 (3.43%) were excluded as they did not meet the inclusion criteria of having 2 nasopharyngeal swabs taken. A total of 4574 nasopharyngeal swabs were taken, with an average of 2 nasopharyngeal swabs taken from each HCW; only 192 HCWs had taken 3 or more nasopharyngeal swabs. A total of 2167 (95.29%) out of 2274 HCWs from the hospital participated in the COVID-19 mass testing during the period 1The median age of the HCWs was 32 years (IQR 28–37), with majority being female . More than half of the HCWs  were in the younger age group (18–34 years). The highest number of professions was contributed by the nurses ; followed by allied health staff ; doctors ; ancillary staffs  and administration staffs . Three-quarters were working in the clinical department  and almost one third were working in the COVID-19 treating area  . Less than one fifth of the HCWs were symptomatic .A total of 19 HCWs tested positive for COVID-19 (0.91%). Their median age was 34 years . All of them were female and most were nurses . Nearly half of the infected HCWs were symptomatic . The symptoms presented were cough (n = 8), fever (n = 5), sore throat (n = 3), runny nose (n = 2), and dyspnea (n = 1).Most of the COVID-19 infected HCWs were infected during the first wave of COVID-19 in Sabah . Fifty eBased on the epidemiological investigation, the source of infection for 8 HCWs were likely in-hospital transmission, 2 HCWs were likely community acquired while the remainder (n = 9) were unidentifiable source of infection.Multivariate logistic regression analysis was done and shown in During the mass testing period, 1 HCW passed away due to cancer, with COVID-19 suspected as an indirect cause. The HCW tested positive through 4 antigen-based rapid test kits (RTK-Ag), but tested negative in RT-PCR tests for nasopharyngeal swabs, tracheal aspirate and tracheal swab.The source of infection was unable to be identified through an epidemiological investigation. However, the HCW had been on medical leave of absence since before the COVID-19 pandemic and was admitted to the ward only during cancer treatment.th March 2020. Vincenzo et al stated that lockdowns are effective in limiting the number of new COVID-19 cases in countries that implemented it, and this benefit could extend beyond 20 days [The mass testing in our public hospital detected only a small percentage of COVID-19 infected HCWs . This percentage is similar to a study done by Oster et al . Majorit 20 days .Most of the infected HCWs were nurses  and had contact exposure to COVID-19 infected person or PUI . This is likely due to the fact that the first infected HCW detected was also a nurse. However, four HCWs  had no evidence of contact exposure to COVID-19 infected person or PUI. Therefore, the mass testing helped in early identification and isolation of HCWs who were not identified through contact tracing. The prompt identification helped in lowering cross-transmission between HCWs, reassuring the families of HCWs and patients, and ensuring the optimal functioning of the hospital during this pandemic .In this study, there was a higher prevalence of COVID-19 positivity from the HCWs working in the clinical department  and the COVID-19 area . This is in contrast to a similar study by Diana et al. who observed a higher prevalence among HCWs from the non-clinical department and non-COVID-19 areas . The difOne mortality was reported among the COVID-19 infected HCWs. The cause of death was due to cancer, with COVID-19 suspected as an indirect cause. Although the RTK-Ag tests were consistently positive, but the post-mortem RT-PCR test results were negative. A systemic review showed false negative RT-PCR tests ranged from 2% to 29%. The viral load for COVID-19 could have been below the detectable level after the death of this HCW .Lastly, the prevalence of symptomatic and asymptomatic COVID-19 infected HCWs were equal, but symptomatic HCWs are almost 3 times of odds of having COVID-19 compared to asymptomatic HCWs. Also, HCWs at age group 51–67 years are about 8 times of odds of having COVID-19 compared to their younger peers. These results highlight the importance of prioritizing screening among symptomatic HCWs and those from an older age group as they are at higher odds of getting infected by the disease. However, this does not mean that the screening of asymptomatic HCWs can be omitted, as they too can transmit the virus if not detected and isolated early [Strategies such as stratified mass testing, strict compliance to the new norm, appropriate PPE usage and identification of high-risk area have been crucial to maintaining a lower number of infections among HCWs. We aim to continue implementing these strategies in accordance to the World Health Organization guidelines.The data was collected from a self-completed form, so they may have been recall bias. Symptoms such as anosmia were not included in the initial registration form, so it was not included in our study. It was not compulsory to answer all questions, resulting in 3 variables  with missing data. The study was conducted in a single institution; hence the data is not representative of other institutions. Future study should include cost-effectiveness evaluation to determine whether the cost can be considered reasonable for the clinical gain.S1 FileSheet 1: Data of all healthcare workers included in data analysis; Sheet 2: Data of all COVID-19 positive healthcare workers; Coding: Label for codes used.(XLSX)Click here for additional data file.S2 File(SAV)Click here for additional data file.


Compared to the 2447 included individuals who never reported SARS-CoV-2 infection, double-vaccinated participants were no more likely to report any of the mentioned symptoms. Vaccination with 2+ doses of BNT162b2 was associated with a reduced risk of reporting most of the common post-acute COVID-19 symptoms. Our results suggest that BNT162b2 vaccination may have a protective effect against longer term COVID-19 symptoms.The effectiveness of Coronavirus disease 2019 (COVID-19) vaccines against the long-term COVID-19 symptoms expressed by a substantial proportion of patients is not well understood. We determined whether vaccination with the BNT162b2 mRNA vaccine was associated with incidence of reporting long-term symptoms post-SARS-CoV-2 infection. We invited individuals PCR-tested for SARS-CoV-2 infection at participating hospitals between March 2020 and November 2021 to fill an online questionnaire that included information about demographics, acute COVID-19 episode and symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated and those uninfected, in terms of post-acute self-reported symptoms. Of the 951 infected, 637(67%) were vaccinated. In the study population, the most prevalent symptoms were: fatigue (22%), headache (20%), weakness of limbs (13%), and persistent muscle pain (10%). After adjusting for age, time from beginning of symptoms to responding to the survey, and baseline symptoms, those who received two vaccine doses were less likely than unvaccinated individuals to report any of these symptoms  by 62%, 50%, 62%, and 66% respectively, (Risk ratios 0.38, 0.50, 0.38, 0.34,  Symptoms of long COVID may fluctuate or relapse over time. Patients purported to have long COVID have reported a wide range of symptoms, but the most prevalent symptoms include fatigue (approximately 58%), shortness of breath (24%), joint pain (19%), chest pain (16%)3, headache (44%), palpitations (11%), physical limitations, depression (12%), and insomnia (11%)4. These symptoms may emerge after the initial recovery from an acute COVID-19 episode or be persistent symptoms that do not resolve following the initial COVID-19 illness5.Long coronavirus disease 2019 (Long COVID), also known as post-COVID-19 syndrome, is an emerging and complex health problem that remains poorly characterised. In October 2021, the World Health Organization (WHO) defined long COVID as “A condition which occurs in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction but also others involving the musculo-skeletal, cardiac and central nervous systems, which generally have an impact on everyday functioning”6. In August 2021, the FDA approved the Pfizer/BioNTech vaccine as the first vaccine for use to prevent COVID-19 in individuals sixteen years and older7. As of October 2021, the WHO has listed the Pfizer/BioNTech, AstraZeneca-SK Bio, Sinopharm, Serum Institute of India, Janssen, and Moderna vaccines for emergency use under the Emergency Use Authorisation (EUA)8. By January 2022, over 58% of the world population had received at least one dose of the EUA COVID-19 vaccines, accounting for 9.2 billion COVID-19 doses6. Available evidence demonstrates that COVID-19 vaccines are effective in preventing severe complications of COVID-19 and death9, including in cases of infection with the Delta and Omicron variants of SARS-CoV-211, variants that are more contagious than the ancestral SARS-CoV-2 variants13.Vaccination against SARS-CoV-2 infection is one of the most important interventions deployed to mitigate the COVID-19 pandemic. The first COVID-19 vaccine campaign with a WHO-approved vaccine started in December 2020, following the authorisation of the Pfizer/BioNTech BNT162b2 mRNA vaccine by the Food and Drug Administration (FDA) for emergency use14 and 45.6% had received a third dose, available in Israel from June 2021. The third dose demonstrated high effectiveness against severe outcomes in the context of waning immunity 6 months post-priming course15. During the study period, individuals previously infected with SARS-CoV-2 were eligible for a single dose of the BNT162b2 mRNA vaccine only. All other individuals with no history of SARS-CoV-2 infection were eligible for a first and a second dose with eligibility for the second dose at three weeks from the date of the first dose. A third booster dose of the of the BNT162b2 messenger RNA vaccine was approved on 30 June 2021 for individuals 60 years and older who have received two doses of COVID-19 vaccine at least five months earlier14.In Israel, the COVID-19 vaccination campaign started in December 2020, and by January 2022, approximately 63.6% of the entire population had received at least two doses, almost all with the BNT162b2 mRNA vaccine16. As the process to establish a more specific case definition of long COVID continues, little is known about the impact of COVID-19 vaccination on long COVID. A large prospective study reported an association between vaccination and lower self-reporting of symptoms beyond 28 days among SARS-CoV-2 infected individuals but without reporting details on specific symptoms or duration17. Findings from one study suggests vaccination reduces the reporting of some, but not all post-acute COVID-19 sequelae 6 months post-infection18. Another study, albeit with a small sample and without a control group, reported a high proportion of COVID-19 breakthrough infections among patients with long COVID symptoms19 (preprint). An additional study reported that 20% of individuals infected post-vaccination developed post-COVID-19 symptoms beyond six weeks, however the investigators did not carry out baseline comparisons20 (preprint). In the current study, we aimed to determine whether vaccination with the BNT162b2 mRNA vaccine was associated with reporting specific long-term symptoms post-SARS-CoV-2 infection.Risk factors for developing long COVID have not been fully explored. So far, increasing age, pre-existing health conditions such as hypertension, obesity, psychiatric disorders, and immunosuppression have been associated with an increased risk of long COVIDOf 79482 invitations to participate in the study, 3572 (4.5%) individuals over the age of 18 agreed to participate: 2447 who reported no previous SARS-CoV-2 infection and 1125 who did. We excluded 174 infected individuals from the study because they did not report their vaccination status.p < 0.05, Table Of the 951 infected individuals included in the study, 340 (36%) reported receiving a single vaccine dose and 294 (31%) reported having received at least two vaccine doses (of which 27 received a third dose). Of the 2447 individuals reporting no previous infection 21 (0.9%) received one dose, 1195 (48.8%) received two doses, 744 (30.4%) received three doses, and the rest were unvaccinated (19.9%). Of the 951 infected individuals, 636 (67%) reported at least one symptom during COVID-19 diagnosis. Among the unvaccinated, 69% reported at least one symptom at COVID-19 diagnosis, vs. 57% among those who received two doses and 74% among those who received one dose only, . The vaccinated and unvaccinated groups were comparable in terms of gender distribution and socio-economic characteristics (Table p < 0.05). The median time from beginning of symptoms to responding to the survey was longest among individuals vaccinated with one dose (11 months), likely reflecting the fact that individuals who received one dose were by and large infected before being vaccinated. Out of 951 infected participants, 85 (9%) reported having been hospitalised with comparable proportions in all groups  reported not fully recovering from the initial COVID-19 symptoms at follow-up. The most commonly reported symptoms at the time of responding to the survey were fatigue 22%), headache (20%), weakness in arms or legs (13%), and persistent muscle pain (10%)  were reported less commonly among those who received at least two doses of vaccine compared with those unvaccinated Table . Most ofIn an exploratory age-stratified analysis, differences in reported symptoms were primarily seen in the older age groups, in particular those aged above 60 years , a finding not consistent with a previous study reporting that the reduced reporting of symptoms was stronger in younger age groups23. It is important to note that our age-stratified analysis was underpowered and studies specifically addressing the effect of age should be conducted before definite conclusions are drawn. Our analysis does not allow us to establish why the reduction of long-term symptoms with the COVID-19 vaccine seems to be greater in older age groups. A plausible explanation for the association found in the older individuals could be that younger individuals have more physiological reserve and are therefore able to recover on their own, which is not the case in older adults. Other studies have reported that frailty was associated with both age and worse outcomes following SARS-CoV-2 infection24.This study brings previously unavailable nuance on the effect of vaccination on reported long-term symptoms, in terms of comparison to baseline incidence of such symptoms, symptom specificity, and time from acute infection. Approximately a third of participants in the current study continued to report post-COVID-19 symptoms, mostly fatigue, headache, and weakness. Our findings are consistent with a recently published study reporting similar proportions of post-COVID-19 symptoms25. As a result, some chronic conditions present at baseline were more common in the vaccinated group. However, since these conditions are more common in the older group who received two doses, we would anticipate even bigger differences between the vaccinated and unvaccinated group had we taken them into account in the analysis. This difference in age between the vaccinated and the unvaccinated individuals is consistent with the COVID-19 vaccination strategy implemented by the Israeli Ministry of Health, which targeted the older population during the initial stages of the COVID-19 vaccination rollout. The vaccinated and unvaccinated populations differed in terms of the proportion of asymptomatic individuals at acute COVID-19 presentation. A higher proportion of those who received two doses were asymptomatic at the time of diagnosis compared to the unvaccinated group, and those who were symptomatic at baseline reported less symptoms compared with those unvaccinated. These figures reflect the possibility of protection against symptomatic disease conferred by vaccines, which may also partly explain the lower proportion of reporting long-term symptoms among those vaccinated. However, the protective effect of vaccination against long-term symptoms persisted after adjusting for asymptomatic disease, suggesting a reduction in reported post-SARS-CoV-2 infection symptoms even among those symptomatic at the time of infection. The median follow-up duration was longer in the unvaccinated group than the individuals vaccinated with two doses. This is consistent with the fact that our follow-up period started nine months before vaccines became available in Israel. Nevertheless, the protective effect of vaccination remained after adjusting for time from beginning of symptoms to responding to the survey. The adjusted model suggested an even stronger protective effect of vaccination against reported long-term symptoms.The unvaccinated and the vaccinated groups were comparable in socio-demographic characteristics except for age, reflecting vaccine coverage in the Israeli population26. Prevention of long-term symptoms could be one of the most important benefits of vaccination in this age group. At the time of this study, children under 12 years were not eligible for COVID-19 vaccines in Israel. A final limitation is the self-reported nature of the symptoms, in particular since individuals who are eager to vaccinate may differ from those who do not vaccinate in terms of perceptions of health and illness. In addition, asking individuals about a list of symptoms they experience enables to quantify but not qualify their experience. Reported fatigue may translate to very different experiences for different individuals with a very different impact on their daily living. Studies that measure the association between vaccination and long COVID in terms of activities of daily living, beyond symptom categories, are needed. We minimised selection bias in this study by inviting all individuals who tested for SARS-CoV-2 at the study sites to participate. However, recall and selection bias inherent to the methodology of cross-sectional population surveys cannot be entirely ruled out. As a final limitation, Israel used almost exclusively the BNT162b2 mRNA vaccine, and the results are therefore only applicable to that vaccine.Our study relied on self-reported positive PCR results and was conducted during a period when PCR testing was freely and widely available to all. In Israel, most individuals have been PCR-tested multiple times for a range of reasons including being symptomatic, travelling, contact tracing, and screening. Specimens for the same patients are tested in different laboratories. Therefore, using positive lab results from a selection of laboratories  could lead to misclassification. Considering the consequences on daily life, including quarantine, it is unlikely that someone would forget having tested positive for SARS-CoV-2, or vice versa. It is however important to note that we could not completely validate that individuals who reported being never-infected, on the basis of never having tested positive, had an infection that was not detected. However, the fact that all individuals in the uninfected group tested negative at least once (and likely multiple times for most) and did not report any acute COVID-19-like episode mitigates the risk of misclassification. It is also important to note that the vaccination policy in Israel, at the time of the survey, specified that SARS-CoV-2-infected individuals were in theory only eligible for a single dose of vaccine. Therefore, individuals who received one dose also differed from those who received two doses in terms of the sequence of events: while those who received two doses have mostly been infected after having been vaccinated, many among those who received a single dose have been infected prior to vaccination. The proportion of individuals eligible for two doses who only received one was small. Although our data does not allow to establish this sequence of events for each individual, the time from beginning of symptoms to responding to the survey reflect this difference. Infection prior to vaccination could partially explain the observed lack of effect of one dose of vaccine regarding long-term reported symptoms. The effect of vaccination on long-term sequelae according to the infection/vaccination sequence warrants further research. With only few patients reporting having been hospitalised, our cohort reflects the mild end of the COVID-19 spectrum, and the results cannot necessarily be extrapolated to patients who were more severely ill  in the acute phase of the illness. Likewise, it is conceivable that individuals severely affected by their post-SARS-CoV-2 infection symptoms were less likely to reply to the survey, and we cannot ensure that the results are generalisable to this category of individuals. Our study did not include children who are less likely to develop severe acute illness following infection but do report long-term effects28, the BNT162b2 mRNA vaccine used in Israel, may be associated with a reduction in the reporting of symptoms post-acute SARS-CoV-2 infection. Despite the methodological limitations described the strength of the effect and the consistency with the existing literature are encouraging. Studies such as this one should be complemented by studies objectively measuring long-term health outcomes in COVID-19 patients in a clinical setting as well as studies investigating plausible biological mechanisms, which may help explain why an association is found with most symptoms, but not all. Our cohort, which continues to recruit participants, will enable us to report with more precision whether the BNT162b2 mRNA’s protective effect reported in this study is sustained, how vaccination impacts on activities of daily living post-COVID, as well as the effect of the different SARS-CoV-2 variants and vaccination on post-COVID symptoms.Our findings suggest that in addition to preventing severe disease and deathThe current study reports results of a cross-sectional study nested in a prospective longitudinal cohort study to assess risk of and risk factors for long-term physical, mental, and psychosocial consequences of COVID-19. All individuals over the age of 18 who were tested for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) between 15 March 2020 and 15 November 2021 in the three major government hospitals in Northern Israel, namely Ziv Medical Centre, Padeh-Poriya Medical Centre, and Galilee Medical Centre, were eligible to join the study regardless of the test result. Using available patient telephone records, individuals were invited to participate in the study between July 16 and November 18, 2021, through a Short Message Service (SMS) containing an invitation with a link to an online survey available in four commonly spoken languages in Israel: Hebrew, Arabic, Russian, and English. Two reminders to complete the survey were sent to non-responders. In this study, we first restricted the analysis to individuals who reported being infected with SARS-CoV-2 and diagnosed by PCR in order to compare vaccinated to unvaccinated individuals in terms of reported long-term outcomes. Because the most commonly reported long-term outcomes reported by COVID-19 patients are not specific to COVID-19, we then compared the frequency of reported symptoms among infected and vaccinated individuals to never-infected individuals.29. The ISARIC questionnaire was adapted to the Israeli context. Study participants were asked to select from a list all symptoms they were currently experiencing.The data collection tool was modified from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 tools developed by a global follow-up working group and informed by a wide range of global stakeholders with expertise in clinical research, outbreak research, infectious disease, epidemiology, respiratory, critical care, rehabilitation, neurology, psychology, rheumatology, cardiology, oncology, and public health medicineThe online survey included information about socio-demographic status , baseline health status: (Body mass index [BMI] and chronic conditions), information related to the clinical experience and symptoms experienced during the initial COVID-19 diagnosis, SARS-CoV-2 test results, vaccination status, number of doses, type of vaccine and date of administration. Participants were also asked to report symptoms experienced at the time of filling the questionnaire. Explicit consent was sought and collected via the online link, prior to collecting any other information.The primary outcome in this study was the proportion, overall, and in specific age groups, of participants reporting selected health outcomes according to vaccination and infection status. It was not possible to determine vaccination status at the time of infection. As a result, some individuals were infected prior to vaccination while others were vaccinated after. Because of vaccination policy in Israel at the time of the study that recommended a single dose for previously infected individuals, it is likely that most individuals who received a single dose were infected prior to vaccination whereas those who received two doses were infected after receiving their vaccines. The complete list of symptoms can be found in Table t-tests (for means). We also compared the proportion of participants presenting with symptomatic disease at baseline using Chi-square tests. Proportions of long-term symptoms and selected health outcomes were calculated for each group with the total number of participants in each group taken as the denominator. We also compared the time elapsed between the onset of COVID-19 symptoms for symptomatic patients and the date of response to the survey in the two groups (vaccinated and unvaccinated).We compared the vaccinated and unvaccinated groups’ socio-demographic and health characteristics using Chi-square tests (for proportions) and Student’s A first series of binomial regression models were fitted to the data of the participants who reported post-COVID-19 symptoms according to vaccination status. We adjusted for age, the difference in time from beginning of symptoms to responding to the survey and proportion of asymptomatic patients at the time of diagnosis between the groups. We then compared vaccinated and infected individuals to never-infected individuals in terms of reported symptoms, also using binomial regression models. The frequency of most of the 39 symptoms and diagnoses reported was too low to meaningfully include in a regression model, and we therefore focused our main analysis on the ten symptoms most commonly reported in the study, although the frequency according to vaccination status is described for all symptoms in Table Vaccination status was recorded as either one dose or two doses. At the time of data collection, a minority of individuals had received a third dose and those who did were recorded as two doses. The third booster dose of the BNT162b2 messenger RNA vaccine was only introduced in June 2021 and for a specific age group (adults 60 years and older).Datasets were processed using Microsoft Excel and analysed using STATA version 15.Further information on research design is available in the Supplementary InfoREPORTING SUMMARY


Hazardous object detection  and avoidance are critical functional safety modules for autonomous mobile cleaning robots. Conventional object detectors have less accuracy for detecting low-feature hazardous objects and have miss detection, and the false classification ratio is high when the object is under occlusion. Miss detection or false classification of hazardous objects poses an operational safety issue for mobile robots. This work presents a deep-learning-based context-aware multi-level information fusion framework for autonomous mobile cleaning robots to detect and avoid hazardous objects with a higher confidence level, even if the object is under occlusion. First, the image-level-contextual-encoding module was proposed and incorporated with the Faster RCNN ResNet 50 object detector model to improve the low-featured and occluded hazardous object detection in an indoor environment. Further, a safe-distance-estimation function was proposed to avoid hazardous objects. It computes the distance of the hazardous object from the robot’s position and steers the robot into a safer zone using detection results and object depth data. The proposed framework was trained with a custom image dataset using fine-tuning techniques and tested in real-time with an in-house-developed mobile cleaning robot, BELUGA. The experimental results show that the proposed algorithm detected the low-featured and occluded hazardous object with a higher confidence level than the conventional object detector and scored an average detection accuracy of 88.71%. Over the last two decades, Autonomous Mobile Cleaning Robots (AMCR) have been promising and viable assistive technologies in the cleaning industry. Chen et al.  mentioneCurrently, AMCR’s navigation system widely utilizes 2D LiDAR and 1D laser sensors ,5, IMU, Object detection using computer vision has been extensively researched for autonomous mobile robot platforms ,11,12,13This work proposes a deep-learning-based context-aware multi-level information fusion framework for an indoor mobile robot to detect and avoid hazardous object detection in its operational environment. First, the image-level-contextual-encoding module was proposed and incorporated with the Faster RCNN ResNet 50 object detector model to improve the performance of hazardous object detection. Then, a safe-distance-estimation function was proposed. It performs the depth data fusion with detection results to compute the distance of the hazardous object from the robot’s position and steer the robot to a safe zone.The rest of the article is structured as follows: Understanding and exploiting context information is a fundamental problem in computer vision, which has been explored extensively and plays a vital role in many fields ,20,21,22Raphael et al.  proposedYu et al.  proposedIn this paper, we incorporated an image-level-contextual-encoding module to the two-stage object detector Faster RCNN to build the context-aware object detector as shown in ResNet 50 Deep Neural Network (DNN) was used as a backbone for our proposed system. It contains 48 convolutions layers and one max pooling and average pooling layer. The first layer includes 64, 7 × 7 kernel convolution with the stride of 2 and 3 × 3 max pooling function with a stride of 2. The next four stages are made up of a mix of residual convolution blocks, and identity blocks contain  trained end-to-end to produce object proposals. It uses the backbone-generated feature map as input and creates object proposals using fixed-size anchor boxes. RPN uses nine different size & ratio anchor boxes and applies a 3 × 3 sliding window function to detect the object in the feature map. After that, each object proposal is assigned a score, with the highest-scoring proposals given the highest priority. This ranking helps to ensure that the most promising proposals are examined first, which can help to save time and computational resources. Besides that, the object proposal with a high degree of overlap is considered redundant and removed by NMS. After the object proposals are scored and ranked, they are fused with the last convolutional feature map of the backbone network. In RoI pooling, each feature region in each object proposal is max-pooled into a regional object feature map with a dimension of 7 × 7 × 512.The image-level context encoding module constructs the global feature map from the backbone-generated feature map. Then, it fuses it with the RPN-generated feature map to bring the clues to the detection head. First, it applies an encoding operation using two parallel dilated convolutional layers with 512 convolutions filters to capture object classes appearing in the entire image. Then, a global average pooling operation is applied to the encoded feature map and sent to feature map fusion and object detection tasks.The context-aware object detection head determines the category of the object contained within each proposal by utilizing an image-level context encoding module 7 × 7 × 512 feature map as well as an RPN-generated 7 × 7 × 512 feature map. In the initial stage, feature map concatenation is performed, where an RPN-generated feature map is fused with an image-level contextual feature map. This process enlarges the feature map depth to 7 × 7 × 1024 dimensions. Then, the concatenated feature map is fed into the object recognition and bounding box refinement module, which detects and classifies the bounding box of the predicted objects in the image. In the end, NMS is applied to eliminate redundant bounding boxes.The safe-distance-estimation function module measures the distance of the hazardous object from the robot’s current position using depth data collected from RGB-D vision sensor data. First, the function takes the bounding box coordinates of the detected object from the RGB image and fetches the respective depth data for each bounding box from the depth image. Then, Realsense rs-measure API  was applThis section evaluates the effectiveness of the context-aware multilevel information fusion framework at three levels: dataset preparation and training, validation with test image datasets, and experimentation with our in-house cleaning audit robot platform, BELUGA .Our dataset contains seven potential hazardous objects, including escalators, moving walkalator, elevators, glass doors, staircases, glass-made display cabinets, and modern furniture. The hazardous objects are labeled with the bounding box annotation tool and have 1200 samples for each class. Furthermore, data augmentation  is applied to all collected images to reduce the CNN learning rate and avoid over-fitting.The context-aware object detection algorithm was developed in TensorFlow 2.13 API and trained using the Nvidia Geforce GTX GPU-enabled workstation. The entire DCNN network was trained using the fine-tuning method in three phases. In the first phase, the backbone, RPN, and context-aware object detection head were fine-tuned with image-Net pre-trained weights for object proposal generation and to detect the objects from the RPN proposals. The loss function of RPN is given in the equations ,,2), i isk is the correct classification.In Equation , yk is 0Accuracy , PrecisEquation ), RecallEquation ), and FmEquation ) IoU (InHere, The experimental results  indicateThe effectiveness of the proposed system was compared with the state-of-the-art object detection methods, including Faster RCNN ResNet 50 and Yolo V4. From a computational point of view, the YOLOv4 framework took less execution time than all other models. Our method has a higher computational time and processes only four images per second, slightly lower than the conventional method. Due to image-level-encoding fusion, our scheme consumes more computation time than the other two methods.The performance analysis results indicate that our proposed method scored better detection accuracy than existing methods. Furthermore, our approach has less miss detection and false classification due to the fusion of global contextual information with object proposal. Therefore, it could increase detection accuracy compared to existing schemes.The real-time field trial experiments were performed in our Singapore University of Technology and Design campus using BELUGA . The detA deep-learning-based context-aware multi-level information fusion framework was proposed for autonomous mobile cleaning robots to detect and avoid hazardous object detection in their operational environment. First, an image-level context encoding module was proposed. Its feature map results were fused with Faster RCNN region proposals to improve the hazardous object detection confidence level and detect the hazardous object on a different level of occlusions. Then, depth data fusion was performed with detection results to compute the distance of the hazardous objects from the robot position. The proposed framework was trained with a custom dataset using a fine-tuning method. Its detection accuracy was evaluated offline with a test image dataset and in real-time using the cleaning audit robot, BELUGA. In our offline test, our proposed scheme scored an average of 88.71% detection accuracy. It processed four images per second and detected the occluded hazardous objects with a higher confidence level than conventional methods such as Faster RCNN and Yolo V4. Compared with existing works, our proposed method scored better detection accuracy for staircase, elevator, glassdoor, and furniture classes. Further, the safe distance estimation map results ensure that our proposed system accurately computed the distance of the hazardous object, which helps steer the robot to a safe zone. Our feature work is the local and global context feature-map-based hazardous object detection for the safe navigation of indoor mobile robots. It could further increase the object detector performance and improve the operational safety of our autonomous mobile cleaning robot.


Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome.™ in Blantyre.We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinIONWe enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen  and steroids  in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0–25.0 p=0.05) compared to the first wave of infection.Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave. We used genome sequencing to identify the variants of SARS-CoV-2 causing disease in Malawi, and found that each of the four waves was caused by a distinct variant. Clinical investigation suggested that the Delta wave had the highest mortality. There is limited COVID-19 genomic surveillance data from low income countries such as Malawi . For patGenomic sequencing is a vital tool to inform strategies for an effective COVID-19 care and treatment response. The early release of the Wuhan-1 genome sequence  enabled In this study we determined SARS-CoV-2 genome sequences from swabs collected from adult patients admitted to Queen Elizabeth Central Hospital (QECH) with PCR-confirmed and symptomatic COVID-19 during four sequential waves of the pandemic. Our aim was to explore the relationship between viral lineage and patient outcome in southern Malawi using an international clinical characterisation protocol. Based on emerging data from other settings –16, we hth March 2021  and were analysed by the Kruskal-Wallis test to compare clinical parameters across the four waves. The primary outcome variable was survival to hospital discharge. We selected the following covariates a priori to determine potential predictors of mortality: pandemic infection wave; vaccine status; age; sex; HIV infection status; prior diagnosis of cardiac disease; prior diagnosis of diabetes mellitus; time from symptoms to hospital admission; respiratory rate; and oxygen saturation , 2nd wave n=94 (December 2020-March 2021), 3rd wave n=97 (June 2021-October 2021) and 4th wave n=75 (December 2021-March 2022). The higher number of participants recruited in waves 2 and 3 reflected the epidemiology of COVID-19 in Malawi  were associated with mortality, although with wide confidence intervals , respiratory rate ≥ 30 (OR 14.87 CI: 3.09 – 71.71) and SpOntervals . Multivantervals . Howeverntervals .Using genomic sequencing we were able to define the viral sub-types or VOCs associated with four distinct waves of patients hospitalised with COVID-19. The first wave was predominantly B.1, all sequenced samples from the second wave were Beta VOC, the sequenced samples from the third wave were predominantly Delta, whilst the samples from the fourth wave were largely Omicron BA.1. Infection with Delta variant was associated with a higher risk of mortality, particularly in patients requiring oxygen during admission. This study reports clinical differences in outcome between SARS-CoV-2 variants in a low-income southern African setting in a population with a high burden of infectious disease, including HIV.The increased risk of mortality in this cohort was associated with increased age (≥70 years) and low oxygen at recruitment (SpO2 <87%), in line with other cohorts . While NICE). This study thus highlights significant inequity in availability of globaly recommended therapeutics for COVID-19 despite relatively high rates of in-patient mortality. It is unclear from this study whether the reduction in severity seen in the Omicron wave was affected by immunity – either vaccine derived or naturally acquired. Overall, 20.9% of the recruited patients in waves three and four were vaccinated with at least one dose (predominantly Astra-Zeneca ChAdOx1-S and J&J Ad26.COV2.S), which is higher than the background population overall, but similar to rates seen in urban Blantyre . However there were already high rates of sero-positivity amongst blood donors in Malawi with 70% of adults SARS-CoV-2 sero-positive in July 2021 during the Delta wave [Throughout the study there was no invasive and very limited non-invasive ventilatory support available for COVID-19 patients and no access to newer therapies such as interleukin-6 antagonists. Therapeutic options for COVID-19 in high income settings are developing rapidly, with genomic viral sequencing used to guide treatments ; bioinformatics software from the scientific community (13); and the infrastructure and funding available to us as an international research institution. The MinION platform has become intergral to outbreak response, as demonstrated for SARS-CoV-2 , Ebola (21) and Zika (22). However, even with this portable and low-maintenance sequencer (with no service contracts or engineer visits required); experienced molecular biologists and bioinformaticians; and considerable international support, it was still very difficult to establish sequencing capability. In particular, we found it extremely challenging to procure reagents, and this was exacerbated by border closures and travel restrictions. As there is no existing policy framework within Malawi for the integration of sequencing data into public health decision making, the utility of our data to decision makers was limited.Our study has several limitations. We produced a relatively small number of sequences. This was partly due to the limited number of patients recruited into the study during each wave but also because patients frequently presented with Ct values too high to generate good quality sequence data. Secondly, our observations are limited to a sample of hospitalised patients in a single centre in the southern region of Malawi. Our relatively low sample size impairs our ability to draw firm conclusions on the association between wave and patient outcome. Finally, we recognize that we may not be capturing the full diversity of SARS-CoV-2 circulating in the community, as our sampling of hospitalised patients represents a considerable bias towards people with severe disease, and there is likely to be significant under ascertainment of cases .In conclusion, pragmatic clinical research protocols coupled with portable sequencing capacity enabled us to improve our understanding of the clinical characteristics and impact of the multiple waves of COVID-19 pandemic in Malawi. We recommend that funders support the development of capacity in genomic surveillance of agents of communicable disease, focussing their strategies on endemic diseases, which can pivot to pandemics and outbreak scenarios as the need arises. A key part of this is the development of robust networks for the production and distribution of molecular biology reagents, mirroring what is being developed for vaccines, as this would enable a more rapid and sustained response to future pandemics. Challenges and opportunities arising from this work are detailed in Box 1. Data and sample collection was enabled by collaboration with the ISARIC consortium. This enabled us to enrol patients very quickly using tools already developed for pandemic response. We were also able to contribute valuable clinical data from a low income setting to global analyses.Supplement 1Supplement 2


COVID-19 pandemic control measures rely on accurate and timely detection of infected individuals. Any defects and delays in diagnosis would negatively impact successful tracing and quarantining of positive cases and can significantly hinder public health control measures . Despite,Molecular-based COVID-19 diagnosis at the ministry of health (MOH) in Jordan has gone through a very interesting success story, starting from only one central laboratory in the capital Amman to 17 laboratories spread out in the country to cover every governorate and travel border  in the capital of Amman. A few PCR non-real time-based genetic tests were performed at Prince Hamza molecular laboratory in Amman as well. When the pandemic hit the country with the first and second transmission waves with increasing aggressiveness, CPHL became overloaded with a huge number of samples to be analyzed from all over the kingdom, including those coming from suspected patients at hospitals and point of care centers and those collected by epidemiological investigation teams. The TAT of testing took an average of 5 to 7 days, which hindered MOH from effectively managing the pandemic .The fact that the private sector and university hospitals that had the capability to perform RT-PCR testing of COVID-19 would charge an average of US$40 per test in the first year of the pandemic, not covered by insurance, drew people to the MOH. The added pressure and overwhelming load posed on CPHL urged the Jordanian government to respond promptly and quickly find solution.As part of the Jordanian government's national COVID-19 response, the MOH collaborated with private pharmaceutical and biotechnology companies to establish COVID-19 PCR testing units in all governorates and at major travel boundaries. By the beginning of 2021, 16 new COVID-19 molecular diagnosis PCR units started to operate, making sure that each governorate has its own facility  with a separate working station for master mix preparation. To meet the construction recommendations for a PCR laboratory, the private companies added partition walls in several sites.In addition to participating pharmaceutical/biotechnology companies, The United States Agency for International Development (USAID) Local Health System Sustainability Project (LHSS) supported the MOH by conducting a comprehensive PCR training program for 79 MOH laboratory technicians from all governorates, including both theoretical and practical aspects. As a result, the PCR testing facility was decentralized to reach all of Jordan's geographic regions.Along with the decentralization process, MOH developed a software system called Sundos to link all laboratories in the country performing RT-PCR diagnosis of COVID-19, including MOH laboratories, university hospitals laboratories, laboratories of military medical services, private laboratories, and laboratories at travel borders. All samples were given digital bar codes and test results were reported to the software system, allowing the MOH to track infected cases and their contacts.The huge expansion in the potential of molecular diagnosis across the kingdom in a relatively short time must have been faced with many serious challenges. Regarding this issue, we interviewed directors of Jordan’s major pharmaceutical/biotechnology companies as part of our ongoing qualitative study aimed at determining the challenges in diagnosing COVID-19 in the Jordanian health sector. This study has not been published yet.We identified shipping and clearance as two major challenges. Air travel restrictions and airfreight market disruption caused the delay in supplying essential health products. There has been a continuing increase in the available flights since April 2020, and thus in the capability for uniform supplies. However, there is still no indication as to when the situation is expected to return to pre-crisis levels. Furthermore, these companies faced a shortage of coronavirus test kits due to huge demand. They also confirmed taking part in designing diagnosis set ups and training laboratory specialists at Jordanian governmental and private hospitals/laboratories according to the WHO regulations based on their experience in the field. A shortage of trained staff was another challenge identified. These challenges were recently reported by a study assessing the capacity of molecular diagnosis of COVID-19 in Jordan .Unlike SARS-CoV and MERS, SARS-CoV-2 spread worldwide at an exceptional rate. In addition to sensitivity and specificity, the development of rapid and high through-put screening testing became a priority. From here, rapid antigen diagnostic tests (ADTs) were developed in hopes to be implemented at POC centers by frontline health care providers for detecting active COVID-19 early infection when timely admittance to molecular testing is not available ,7. RapidIn 2020 and the beginning of 2021, Jordanian authorities put many restrictions on the types of commercial tests to be used through the Jordanian Food and Drug Administration (JFDA). Rapid lateral flow assays for detection of antigens were not allowed, while the use of immunoassays for antibody detection was approved. These included enzyme linked immunosorbent assay (ELISA), chemiluminescence-based platform and fluorescence-based platform with European Committee (EC), or Food and Drug Administration (FDA) quality certificates. Among the most common commercially available automated instruments used in Jordan are ARCHITECT SARS-CoV-2 N IgG Immunoassay , LIAISON® SARS-CoV-2 S1/S2 IgG , Elecsys® N Anti-SARS-CoV-2 , VIDAS® SARS-COV-2 RBD IgG , Siemens SARS-CoV-2 RBD Total (COV2T) , Access SARS-CoV-2 RBD IgG assay , POC instrument FREND SP IgG/IgM , and Ichroma COVID-19 Ab (Ichroma /Korea).In March 2021, the MOH, in cooperation with USAID LHSS, launched a practical training program on performing rapid ADTs for COVID-19 diagnosis. ADT use was limited to large hospitals only, including MOH hospitals and Royal Medical Services hospitals, along with the University of Jordan Hospital, King Abdullah I Hospital, the National Diabetes Center and the King Hussein Cancer Center. The JFDA only approved EC or FDA quality certified kits with sensitivity and specificity not less than 97% and 99%, respectively .In February 2022, the Jordanian Pharmacists Union urged the government to allow pharmacies to perform ADTs for potential COVID-19 infections . By ApriThis article tells an untold story of the enormous expansion of molecular diagnosis of COVID-19 driven by MOH in Jordan. Starting from a central laboratory in the capital Amman, RT-PCR units were established in every governorate as well as travel borders to cover the whole country.Many benefits have been achieved during the two years of pandemic. In a recent assessment of COVID-19 molecular diagnosis in the country, the number of PCR tests conducted per day significantly increased over time in correlation with the decentralization act . This ex


C-glucosyl moiety in bioactive compounds, we aim to raise awareness of the importance of contemplating the shift to (poly)phenol–carbohydrate combinations in the development of functional nutrients, as well as in the early stages of antidiabetic drug discovery.The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective compounds for type 2 diabetes based on the structure of natural (poly)phenols are remarkable and have indeed proven worthwhile after the introduction of gliflozins in clinical practice. However, low-quality reports on the antidiabetic potential of plant-derived lipophilic (poly)phenols continue to pile up in the literature. Many of these compounds continue to be published as promising functional nutrients and antidiabetic pharmaceutical leads without consideration of their Pan-Assay Interference Compounds (PAINS) profile. This evidence-based opinion article conveys the authors’ perspectives on the natural (poly)phenol artillery as a valuable and reliable source of bioactive compounds for diabetes. Ultimately, in light of the already established membrane-perturbing behavior of lipophilic (poly)phenols, together with the multiple benefits that may come with the introduction of a  According to the International Diabetes Federation (IDF), 537 million adults are presently living with diabetes, which corresponds to a global prevalence of 10.5% . DietaryFrom in vitro to clinical studies, the number of published reports covering the potential of dietary lipophilic (poly)phenols to treat diabetes and its comorbidities is countless ,8. ResveC-glucoside of phloretin, nothofagin , did not follow the aglycone in its promiscuous behavior. These results were impeccably corroborated by C-glucosyl resveratrol and C-glucosyl genistein—so much so that C-glucosylation was proposed as a tool to prevent PAINS-induced membrane dipole potential alterations [In the context of medicinal chemistry applied to drug discovery, Pan-Assay Interference Compounds (PAINS) were described for the first time in 2010 as molecules with structural features that are able to interfere with drug screening assays, often leading to false positive results . This coerations . Here, ierations . As chanC-glucosyl (poly)phenols are able to prevent membrane dipole potential alterations caused by (poly)phenol PAINS are unknown, there are some theories. As highlighted elsewhere [C-glucosyl polyphenols are so unique in achieving this effect when compared to their O-glucosyl counterparts. Nonetheless, fewer rotatable bonds arising from the replacement of the anomeric C-O-C triad by a C-C bond is expected to result in enhanced molecular rigidity, which ought to more favorably sustain the conformation of the molecule that promotes proper membrane insertion for minimal changes to the membrane dipole potential.Although the exact mechanisms by which lsewhere , these clsewhere . FurtherC-glucosylation can in fact be used as a general way of converting membrane-disrupting lipophilic polyphenols into non-IMP (poly)phenols for a wider range of molecular entities. In this context, however, it is also important to reinforce that such a strategy would only be valid for (poly)phenols that do not check the box for other types of PAINS/IMPS features, and many of them actually do. Catechol and hydroquinone moieties, which are very frequently found in natural products, are both prone to autoxidation followed by covalent modification, likely leading to the formation of multiple and non-specific protein adducts often masked as protein aggregation inhibition [More extensive experiments are warranted to confirm the hypothesis that hibition ,20,21. TC-glucosylation should be considered when it comes to the pursuit of non-reactive lipophilic (poly)phenols with antidiabetic properties: (1) C-glucosides extracted from natural plant sources are increasingly recognized as functional ingredients for their potent antihyperglycaemic, anti-aggregation, and antioxidant bioactivities, both alone or in combination with other antidiabetic compounds [O-glycosides, their (poly)phenol C-glucosyl analogs may also lead to improved selectivity and metabolic stability [C-glucosyl aromatic compounds originally developed and approved as SGLT2 inhibitors for the treatment of type 2 diabetes [50 25,000 nM vs. SGLT1 IC50 50,000 nM [O-glucosyl moiety phenols that do pass that stage, there are strong hints that ompounds ,24,25,26ompounds ,28,29;  tability . Let us diabetes . The pridiabetes . This lo0,000 nM ) sees it0–499 nM ,32), but9,000 nM ) phenol-based functional nutrients and drug-like molecules. We recommend testing natural (poly)phenols regarding membrane interference prior to being published for their promising bioactivity in cell-based assays phenol C-glucosylation is entirely feasible both synthetically and through biotransformation, with an increasing number of methodologies being created and made available to the scientific community [All in all, gliflozins serve as a great illustrative example of the power of d assays , hence community ,35,36.Finally, it should also be made clear that while the rationale herein proposed focuses on the development of small compounds with robust antidiabetic activity against specific molecular targets for the treatment and management of type 2 diabetes, this does not imply that dietary non-glycosylated lipophilic (poly)phenols cannot have an important adjuvant role with regard to the prevention of this condition. In fact, lipophilic (poly)phenols have been shown to positively modulate the composition of gut microbiota, including the above-described IMPS resveratrol and curcumin ,37.With C-glucosides deserve more credit than they have been given as lead molecules for both the development of functional food ingredients and pharmaceuticals for type 2 diabetes. Aromatic C-glucosylation is feasible through a variety of methods, and has not only been proven to enable the fine-tuning of (poly)phenol antidiabetic effects and drug-like properties, but has also led to tangible results when it comes to the discovery of nature-inspired molecules able to make a difference in the treatment of type 2 diabetes and its comorbidities, as exemplified with the case of gliflozins. There is no question that natural (poly)phenols are valuable sources of active scaffolds; the question is simply about understanding how to use them and, above all, how to make them thrive.In summary, given their potential for improved bioactivity and non-PAINS profile regarding membrane disruption, polyphenol


Healthcare workers (HCWs) stand the risk of acquiring infection directly, while attending to patients or indirectly while handling and testing patient specimens. Considering this, the present study was planned to assess Personal Protective Equipment (PPE) breaches and exposures among HCWs working in COVID-19 wards/ screening areas and to evaluate their COVID-19 positivity rates post-exposure concerning the level of exposure, type of PPE breach, and the cadre of HCWs exposed in COVID-19 wards.This retrospective cross-sectional study involved the analysis of all instances of PPE breaches which occurred during a period of nine months from June 2020 to February 2021 at a tertiary care level hospital in Central India. The analysis included all exposures involving any cadre of HCWs that occurred while handling the patients or while doffing the contaminated PPE in COVID -19 wards.A total of 347 PPE breaches were analyzed from the available records of the Hospital Infection Control team repository. Amongst the 347 breaches, 268 (77.2%) were classified as low-risk exposures and 79 (22.8%) as high-risk exposures. Cadre wise distribution of high and low-risk exposures revealed that, PPE breaches occurred most commonly in the category of nursing officers . Among all of the breaches, 15.2% of high-risk exposures and 2.6% of low-risk exposures resulted in COVID-19 positivity with a cumulative positivity of 5.4%. Collectively, non-mask related breaches accounted for the majority (63.2%) of the positive COVID-19 cases.Appropriate use of PPE by HCWs is vital for their protection. However, breaches in the use of PPE may occur while managing COVID-19 patients due to physical and mental exhaustion among HCWs resulting from work overload. Early identification and appropriate management of HCWs with high-risk exposures can help prevent transmission to other hospital staff and patients, thus preserving resources and workforce. CoronavHealthcare workers (HCWs) consist of all paid and unpaid persons serving in healthcare settings who have the potential for direct or indirect exposure to patients or their infectious materials, including body substances ; contaminated medical supplies, devices, and equipment; contaminated environmental surfaces; or contaminated air. HCWs consist of but are not limited to doctors, nurses, medical laboratory scientists, maintenance staff, clinical trainees, volunteers, emergency medical service personnel, nursing assistants, home healthcare personnel, technicians, therapists, phlebotomists, pharmacists, dental healthcare personnel, students and trainees and contractual staff . They arPersonal protective equipment (PPE) offers considerable protection against occupational exposure to SARS-CoV-2 in addition to the basic infection prevention measures including hand hygiene and distancing. Recommendations regarding appropriate usage of PPE have been issued by national and international organizations like the World Health Organization (WHO), Centre for Disease Control (CDC) and the India Ministry of Health and Family Welfare (MOHFW) which have also been updated from time to time. Based upon the latter recommendations, every health care facility has also formulated guidelines for proper use of PPE with standardized donning and doffing protocols in COVID-19 areas to minimize the chances of acquiring infection. HCWs have also been provided regular training on the correct techniques of donning and doffing of PPE.However, even after abiding with the recommended PPE protocol, while working with COVID-19 patients, an accidental breach in the protection may occur. This may happen during emergencies or during routine care due to various factors including improper methods of donning and doffing of PPE, poor visibility due to fogging of eye goggles and suboptimal quality of PPE. Such breaches need to be assessed thoroughly to decide upon the management of exposed HCWs. As per WHO as well as MOHFW recommendations, HCWs with high-risk exposures require monitoring for the development of infection and quarantine followed by testing for SARS- CoV -2 to prevent further transmission. This approach is directed towards preserving the workforce required to preserve essential services. On the other hand, many of the exposures may not always lead to infection. Considering this, it is important to review the nature and extent of PPE breaches that have occurred during COVID-19 patient care, to identify the most common types/ patterns of breaches that occurred and their significance in causing SARS-CoV-2 positivity among HCWs.This information will help to facilitate PPE use protocols and will generate evidence that can be shared during training and sensitization programs in-house as well as with peer institutions to devise/modify the preventive strategies. Accordingly, the present study was planned to assess the PPE breaches/ exposures among HCWs working in COVID-19 wards/ screening areas and to evaluate their COVID positivity rates post-exposure concerning the level of exposure, type of PPE breach, and the cadre of HCWs exposed in COVID-19 wards.This retrospective cross-sectional study involved the analysis of all instances of PPE breaches which occurred during a period of nine months from June 2020 to February 2021 at a tertiary care level hospital in Central India. The analysis included all exposures involving any cadre of HCWs that occurred while handling the patients or while doffing contaminated PPE in COVID-19 wards. Only those exposures which were noticed by or reported to the infection control team were included in the study. Exposures due to interaction with a positive case outside the COVID wards or any kind of community exposures were excluded from the study.The COVID-19 area of our hospital is basically a three tier system. There is a screening zone where suspected patients are screened for COVID-19. The positive patients are admitted into the COVID-19 ward and any seriously ill patients are shifted to the COVID-19 ICU of our hospital.In our hospital, all HCWs working in COVID wards/ICUs are required to wear the following PPE: N95 mask, goggles/face shield, cap, coverall with hood, two pairs of gloves, and shoe covers. Detailed recommendations can be found in All HCWs prior to their posting at COVID wards were provided with obligatory hands-on training on PPE donning and doffing (including N95 fit checking) by the hospital’s infection control staff. On-site hand-holding sessions were also held for HCWs who were having trouble donning and doffing their PPE. Furthermore, instructive videos on donning and doffing of full and individual PPE were developed and distributed to all healthcare staff.The hospital has a well-defined mechanism to observe and report PPE breaches/ incidents of potential exposures occurring on COVID wards and the rational use of PPE as advised by the MOHFW is thoroughly followed . MonitorHigh-risk exposure:HCW or other person providing care to a COVID-19 case or lab worker handling respiratory specimens from COVID-19 cases without recommended PPE or with a possible breach of PPEHCWs performing aerosol-generating procedures without appropriate PPE.HCWs without mask/face-shield/goggles:○ having face to face contact with a COVID-19 case within 1 meter for more than 15 minutes○ having accidental exposure to body fluids or having unprotected direct contact with the infectious secretions from a patient with COVID-19 or a contaminated patient care environment.Low-risk exposure:Contact with a person with COVID-19 having not met criteria for high-risk exposure .All the HCWs posted in COVID-19 wards were provided with residence within dedicated rooms within the hospital’s campus, as some of them were hesitant to go back to their homes in off-duty hours. If they had high-risk exposures during duty, they were immediately quarantined and tested for SARS-CoV-2 on or after 7 days of exposure or if they became symptomatic as per the hospital’s policy. Until tested negative, HCWs observed quarantine and continued to do so till 14 days post exposure. Those HCWs with low-risk exposures on the other hand were not strictly quarantined and were allowed to continue working while self-monitoring their symptoms and residing in the institutional residential facility even after the exposure. The Infection Control team followed up on the HCWs who had high-risk exposures for their COVID-19 testing status after 7 days. Those who tested positive were advised to get clinical care after consultation with doctors posted on the COVID-19 wards. HCWs with low-risk exposure were tested for COVID-19 if they experienced symptoms after 7 days, or voluntarily even if they were asymptomatic after 7 days for fear of testing positive. In such cases, laboratory records were used to determine the status of COVID-19 positivity.The study involved evaluation of all such exposures that had occurred during the study period retrospectively through review of records on breach incidents. Reports on COVID-19 positivity among the HCWs were retrieved from the records possessed by the Infection Control team and Microbiology laboratory.The data were collected and tabulated in an Excel (Microsoft Inc.) sheet. The data were analyzed for proportions of high and low-risk exposures concerning types of PPE breach and type of HCW cadre affected. Appropriate statistical analysis was done applying appropriate statistical tests using SPSS version 22.0 software.The study was approved by the Institute Ethics Committee review board of the All India Institute of Medical Sciences Raipur, India. The study was conducted according to the principles expressed in the Declaration of Helsinki. .This retrospective study was carried out over nine months spanning from June 2020 to February 2021. A total of 347 PPE breaches were analysed from the available records of the Hospital Infection Control team repository with 268 (77.2%) breaches classified as low-risk exposures and 79 (22.8%) breaches classified as high-risk exposures .Cadre wise distribution of high and low-risk exposures revealed that maximum PPE breaches/exposures occurred in the category of nursing officers  followed by doctors , housekeeping staff  and Radiodiagnosis technicians  . Out of Exposures were also categorized according to the breaches observed with various components of PPE like gloves, masks, coverall gowns, goggles. These were classified into low or high-risk exposures as described in As shown in The odds ratio was found to be 2.07 (95% CI 0.79 to 5.46) which implies that getting COVID-19 positivity is almost two times higher amongst high-risk exposures as compared to the low-risk exposures.Our findings suggest the best way for HCWs to prevent infection with SARS-CoV-2 is through training and demonstrated competency in putting on and removing PPE, also known as donning and doffing . Our finEven after following all possible infection control guidelines, our findings illustrate that breaches may occur due to a number of reasons, resulting in variable levels of low- and high- risk exposures. Potential causes may include a combination of physical events and mental exhaustion resulting from work overload, improper self-care, or other situations outside the medical facilities .It is worth noting that not all PPE breaches lead to high-risk exposures and not all high-risk exposures will lead to infection in the HCWs. The present study demonstrates a positivity rate of 15.2% and 2.8% for COVID-19 among the high-risk exposure and low-risk exposure groups respectively. The positivity among low-risk exposure groups may not be solely attributed to PPE violations, as there may be the possibility of unknown and unidentified exposures outside the work area. An analysis of COVID-19 transmission dynamics from a pediatric COVID- 19 care center demonstrated almost 70% (29 out of 42) of the positivity among HCWs without high-risk exposure in the hospital were classified as likely community-acquired . A crossAs described previously, positivity in the low-risk group was not totally associated with exposures at the workplace as the exposed individuals were not strictly quarantined and might had exposures in shared spaces or outside the workplace as there was no restriction for them to visit homes/community places during the off-duty hours as opposed to the high-risk exposure group. The positivity in the high-risk exposure group, on the other hand, can be linked to the workplace related exposures because these HCWs were strictly quarantined immediately after the exposure without further contact with unknown sources in the community or at shared workplaces. Even knowing this, the probability of contracting an infection through community exposures before coming into contact with a low or high-risk exposure at work cannot be completely eliminated. Hence, generating knowledge about the kinds of ICP breaches that are usually experienced by HCWs with its outcome is necessary and can guide upon future strategies to deal with the crisis.The risk of transmission of SARS- CoV-2 may be related to the component of PPE used in the breach occurrence. In the present study, breaches in various components of PPE were observed. Amongst all, the most common breach observed was with the use of gloves, due to frequent tearing of gloves while doffing/working with them and due to needle stick injuries. However, it resulted in COVID- 19 positivity among 3.0% HCWs. A sizeable number of needle stick injury cases among the HCWs were observed, however, none of them resulted in COVID- 19 positivity. A breach in other components of PPE such as masking, coverall gown, goggles, and improper doffing was also observed. Chou et al  in theirThe transmission of SARS CoV-2 is principally through droplet infection and direct/indirect contact . In our Our study showed that breaches were scattered across staff groups, and it was reported that breaches were most common among the nursing officers probably because of their wider representation among all types of HCWs and continuous involvement in inpatient care.Investigating common breaches identifies possible routes of infection, establishes recommendations for improving PPE design, and enables IPC teams to educate HCWs accordingly.For a reduction in PPE breaches by the HCWs, further work needs to be done. ‘Eagle-eyed observer’ approach as suggested by Peng et al is an example that can detect and correct PPE breaches by health care workers . FurtherOur study sheds light on the behavioral aspects/areas where HCWs can go wrong in their knowledge/perception and actual emphasis when it comes to adherence to PPE protocol and its proper use when working in a challenging environment. Many of the breaches happened because HCWs were in a rush to complete their duties within a certain amount of time while working in unfavorable settings, which is a unique issue in COVID- 19 wards. Continuous use of PPE has reported to significantly cause physical and neurological dysfunctions such as, headache/irritability, the urge to doff among the HCWs and causing nausea and difficulty in decision making [Our findings will improve future HCW education and training to help them avoid typical errors such as poor wearing of masks and goggles, which can lead to easy removal/displacement, and inappropriate doffing of these and other PPE, such as gloves, which can lead to contamination of hands. Hand hygiene’s importance can be emphasized even further by providing hands-on training in this crucial area. It also prompts a thorough examination of concerns relating to the quality of PPE used in the wards  and helping the hospital administration in selecting the most appropriate products for safe use.The passive nature of collection of information is one of the major limitations of the study. However, data on PPE breaches in subsequent waves will add to our knowledge in this area. To our knowledge this is the first study of its kind in India which assesses the type of PPE breaches among HCWs working in COVID-19 areas and subsequent positivity associated with the breach and our detailed analysis adds unique insights. Furthermore, to minimize the reporting bias, information collection and verification was done at multiple levels including immediately informing the infection control nurse (ICN) posted in the COVID-19 area and categorizing the breach as high- risk or low-risk followed by further verification by the Hospital infection control officer.HCWs being the frontline staff in handling the COVID-19 crisis are at a higher risk of acquiring infection. Appropriate use of PPE by HCWs is vital for their protection. Additionally, training on the appropriate use of PPE and other ICP measures, supervision and monitoring of ICPs can enhance the effectiveness of these interventions. However, despite all mechanisms in place, a breach in the PPE may occur while managing COVID-19 patients due to physical and mental exhaustion among HCWs resulting from work overload. Early identification and appropriate management of HCWs with both low- and high-risk exposures can prevent transmission to other hospital staff, saving resources and workforce.S1 File(PDF)Click here for additional data file.


During the Covid-19 pandemic, individual and collective public health measures were undertaken to control the spread of the virus. Their effectiveness relies on people’s abilities to understand and adopt the correct behaviors. This study aims to evaluate the role of Health Literacy (HL) in influencing the adherence to Covid-19 preventive measures and risk perception of a sample of workers employed in various activities involving close contact with the population in the province of Prato  in the second pandemic wave (November-December 2020). A cross-sectional survey was conducted on a sample of public workers . Data on knowledge, attitudes and practices towards (KAP) Covid-19 preventive measures and risk perception were collected. HL was measured with the HLS-EU-Q6 tool. Spearman correlation analysis was used to assess the correlation between HL and KAP and Covid-19 risk perception. Multivariate linear regression analyses were performed to evaluate the role of HL in predicting KAP and Covid-19 risk perception, adjusted for sex, age, comorbidity, educational level, country of birth. A total of 402 people participated in this study; 47.8% had a problematic HL level. The HL level was correlated with KAP and practices towards Covid-19 prevention measures; no significant associations were found with Covid-19 risk perception. In multivariate models, HL significantly and positively predicted a higher level of knowledge of Covid-19 preventive measures . Confirming a previous study conducted in Prato in the first pandemic wave, HL did not predict adherence to Covid-19 infection control measures, probably due to fear of the disease and attention towards prevention behaviors being still higher in the second pandemic wave.• HL skills are linked to understanding of public health measures.• HL skills should be improved to favor the adherence to correct behaviors.


The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited.To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission.A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan–Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes.Antibiotics were prescribed to 13.2% (Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients. The Coronavirus Disease 2019 (COVID-19) burden among children in Mexico has been high  of hospital discharge of children hospitalized due to COVID-19.Clinical specimens  were analyzed (SuperScript™ III Platinum™ One-Step qRT-PCR Kits) at four specialized regional laboratories integrated into the IMSS network for epidemiologic surveillance. A broader description of the laboratory methods has already been published elsewhere .We computed summary statistics and the significance level (α) at 5%. The Kaplan–Meier method calculated survival functions and 95% confidence intervals (CI). The log-rank test was used to compare the survival distributions of the study groups. The effect of the prescription of antibiotics (any) was evaluated through hazard ratios (HR), and 95% CI was computed using a multivariate Cox proportional hazard regression model. All analyses were conducted using Stata version 16.0 .Data from 1601 patients were analyzed for a total follow-up of 16,238 person-days. Figure The overall rate of a fatal in-hospital outcome was 9.3  of the rate documented by a previously published Latin-American multicenter study where most of the analyzed patients were from Peru and Costa Rica . Our ratWe hypothesize that two factors may be determined, at least partially, by the low rates of antibiotic prescription documented in our study. The first is that all hospitals from where patients were recruited were public settings belonging to IMSS. For-profit hospitals have been associated with a higher risk of receiving these drugs . The secThe main factors determining the start of antibiotics seem to be increased inflammatory markers, and any infiltrate on an x-ray image . In our The empirical prescription of antibiotics in COVID-19 patients does not reduce the risk for severe symptoms or death . The cliThe overuse of antibiotics in patients with COVID-19, especially combinations of broad-spectrum antibiotics, has become a significant concern . FightinThe potential limitations of our study must be cited. First, data regarding the prescription of antibiotics were collected as a dichotomous variable, and other clinical and epidemiological relevant information (such as length of administration) was omitted. We also documented that in around 40% of inpatients, the precisely prescribed antibiotic was not registered. Second, we did not evaluate intermediate outcomes such as the multisystem inflammatory syndrome temporally related to COVID-19 , which mOur findings suggest that antibiotic prescription in children inpatients with COVID-19 is associated with an increased risk for fatal outcome. If later replicated in other populations, our results highlight the major relevance of limiting the empirical administration of anti-bacterial drugs in these patients.


Computed tomography-guided hook wire localization (CT-GHWL) was used to localize the small pulmonary nodules before video-assisted thoracic surgery (VATS). Its associated complications included hook wire dislodgement, pulmonary hemorrhage, and pneumothorax. This is the first report of a patient with a hook wire sliding into the subglottic area after CT-GHWL.A 27-year-old female had productive cough for 8 days. A high-resolution CT scan showed a 12 mm part-solid nodule in the number 8 segment of the left lung. Prior to VATS, she received CT-GHWL to localize the nodule. During VATS, the hook wire unexpectedly slid away. A chest computed tomography was immediately performed and the sagittal reconstructed images showed the needle at the subglottic area. Finally, the needle was extracted by biopsy forceps under bronchoscope evaluation. The patient was eventually recovered and discharged.Dislodge of the hook wire into the subglottic area is an extremely rare but serious complication following CT-GHWL. Attention should be paid to securing the needle on the lung surface during VATS. With the advent of computed tomography screening for lung cancer, an increasing number of patients have been found to have small and undetermined pulmonary nodules, especially ground-glass opacity nodules (GGNs) . Video-aA 27-year-old female had productive cough for 8 days, with no response to the levofloxacin treatment. A high-resolution CT scan showed a 12 mm part-solid nodule (consolidation to tumor ratio 0.17) that was located centrally in the number 8 segment of left lung (LS8)  The hook wire entered the small bronchus during the process of CT positioning. During the VATS operation, when the lung was manipulated repeatedly, the hook wire could only move forward due to the barb on its tip, resulting in hook wire swimming. 2) Once the operator found that the needle was missing, he repeatedly palpated the main bronchus by hand to search for the needle, which could have squeezed the needle into the main bronchus, resulting in hook wire swimming. 3) When the endotracheal tube was removed from the patient, the endotracheal tube brought the hook wire from the left main bronchus to the subglottic area. Because the glottis was relatively narrow, the hook wire was stuck under the glottis.In our patient, the design of the mammography localization set might be the reason for the unexpected hook wire slide away into the lung. Previous studies also reported the slides of the similar hook wire into the left upper lobe pulmonary artery or the splenic artery , 8. AnotIn conclusion, we reported the first case of the hook wire sliding into the subglottic area during CT-GHWL. The following lessons were learned from this case study. When the hook wire is found on the lung surface during VATS, it should be immediately secured on the lung surface with the surgical forceps or hemolock to prevent dislodge of the guide wire. Once the hook wire disappears from the surgical field, a CT examination should be performed immediately to look for the needle. Every effort should be attempted to localize and remove the dislodged needle.