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Aim

This study aimed to evaluate the immune response and vertical transmission of anti-severe acute respiratory syndrome (SARS) antibodies in vaccinated, expectant mothers infected with coronavirus disease 2019 (COVID-19) and to study the sequelae.

This was a retrospective study of pregnant women conducted at Bahrain Defense Force Hospital from March 2021 to September 2021. The study population was divided into two groups: group 1 was vaccinated with Sinopharm or Pfizer/BioNTech during pregnancy and never infected with COVID-19. Group 2 was unvaccinated and had been infected with COVID-19. Immune responses such as anti-nucleocapsid (anti-N) and anti-spike (anti-S) from paired samples of maternal and umbilical cord blood were measured with Elecsys immunoassay (Roche Holding AG: Basel, Switzerland) at the time of delivery. Obstetric complications such as preterm labor, preeclampsia, and stillbirth were assessed. Analysis was performed using SPSS version 26.0 (IBM Corp: Armonk, NY)and Minitab version 18 (Minitab, LLC: State College, PA). A p-value of less than 0.05 was considered statistically significant.

The study included 90 vaccinated and 90 COVID-19-recovered pregnant women. Matched samples were available for 80 vaccinated and 74 COVID-19-recovered women. Group 1 had significantly higher levels of anti-S for both the mother and the cord blood and a significantly higher transfer ratio of anti-S. Group 2 had higher levels of anti-N. In group 1, the paired sample titer of anti-S had a weak negative correlation with maternal age whereas, in group 2, the mothers anti-N had a weak positive correlation with age. Antibodies of COVID-19-recovered mothers and cord blood had a moderate negative correlation with gestational age, except for the mothers anti-N. In group 1, the transfer ratio of anti-N and anti-S had a statistically significant association with gestational age. Preterm delivery had a high prevalence of anti-transfer ratios of <1, and delivery at >37 weeks had a high prevalence of 1. In group 2, 90% of preterm deliveries had transfer ratios of anti-S <1. The latency period of the COVID-19 group had a statistically significant association with the antibody transfer ratio. An interval of less than 100 days had a high prevalence in the ratio of <1.An interval of more than 100 days had a high prevalence in the ratio of 1. There was no significant latency period in group 1. Group 1 had a 75% prevalence of an anti-S transfer ratio 1 with a birth weight of >3500 g; group 2 had no significance in birth weight. We did not find significance in the sequelae of morbidities in either group.

The production of the antibody N in the COVID-19-infected and antibody S in the vaccinated pregnant women as well as the vertical transmission of antibodies was efficacious. Significant variation was found regarding maternal age in both groups. The transfer ratio of the antibodies in the vaccinated and COVID-19-recovered women was significantly higher in terms of babies of the vaccinated and the infected population. The transfer ratios were distinct according to the latency period and birth weight of the infants.

The severity of coronavirus disease 2019 (COVID-19) increases during pregnancy, and the virus has been associated with maternal and fetal morbidities such as critical care admission during COVID-19 infection, venous thromboembolism, preeclampsia, and preterm labor [1-3]. The COVID-19 vaccine is a promising protective approach to reducing the incidence of morbidities during pregnancy. Currently, the COVID-19 vaccines are recommended for pregnant women worldwide; the benefits are greater than the risks. The UKs Joint Committee on Vaccination and Immunization recommends vaccination for all pregnant women before 27 weeks because disease severity increases after this period [4]. The approved vaccines are not live, so they cannot cause actual disease in the women or the fetuses [5]. Quantifying the immune response of the vaccinated vs. the infected pregnant women as well as vertical transmission is important in understanding how to protect against infection. Comparing the immune response of the COVID-19-infected and vaccinating pregnant women is crucial for future recommendations for the pregnant population.

The study was conducted in our tertiary center, Bahrain Defense Force Hospital, from March to September 2021. It began with receiving informed consent and included 180 pregnant women. The study design was approved by our research centers ethical committee and the national COVID-19 clinical research team. The cohort was divided into group 1, which included 80 vaccinated, and non-infected pregnant women, and group 2, which included 74 non-vaccinated, and COVID-19-recovered pregnant women. Infection was excluded by nasopharyngeal samples using the polymerase chain reaction (PCR) or SARS-CoV-2 GeneXpert before checking antibody levels. Twenty-five people were not included in our analysis of immune responses because matched sera were not available. Demographic data were assessed in detail. Evaluation of computerized records was done confidentially. All data were rendered anonymous. The cohort was interviewed about the types of vaccines they had received, their gestational ages at their first and second doses, and their COVID-19 diagnoses. The gestational age at delivery and interval of immunoassay were calculated. Antibodies from both groups in response to the spike protein (S) and nucleocapsid protein (N) and their vertical transmission were assessed using the mothers serum at the time of delivery. Interval frequencies of antibodies from the second vaccine dose and from COVID-19 infection were calculated. The association of immune response with maternal factors, including maternal age, BMI, gestational period, gestational age at delivery, latency period, and transfer ratio, was calculated and compared between the groups. The transfer ratio level was divided; and the association with maternal age, BMI, gestational age at delivery, gender of the baby, birth weight of the baby, and latency period was checked in both groups. Cohorts were continuously assessed for sequelae following vaccination and COVID-19 infection. Both populations were assessed throughout pregnancy to identify complications.

Group 1 included vaccinated pregnant women who received two doses during pregnancy and had matched paired samples of umbilical cord blood. Group 2 included women who were infected with COVID-19 and had paired samples. In both groups, participants with and without matched samples were included in the analysis of sequelae.

To ensure uniformity, individuals in group 1 who received single dose or booster doses of vaccination were excluded. To reduce bias, anyone who was infected with COVID-19 at any point during or before pregnancy or got vaccinated before pregnancy was also excluded. Group 2 excluded women vaccinated before and during pregnancy. The population without matched sera was excluded from antibody analysis.

Continuous variables were represented asmeanstandard deviation, or median (first quartile, third quartile), whereas categorical variables were represented as frequencies and percentages. Depending on the data requirements, independent t-test and Mann-Whitney U test were used to compare the characteristics of the vaccinated group and the COVID-19 infection group. Pearson and Spearman correlations were used to assess the relationship between maternal factors, mother's antibodies, cord blood antibodies, and antibody transfer ratio. To assess associations between categorical variables, chi-square and Fisher's exact tests were used. SPSS version 26.0 (IBM Corp: Armonk, NY)and Minitab version 18 (Minitab, LLC: State College, PA) software were used to conduct all analyses. A p-value of less than 0.05 was considered statistically significant.

The analysis included a total of 154 women, 80 of whom were vaccinated while pregnant and the other 74 were infected with COVID-19 while pregnant. The patients' ageranged from 18 to 42 years, with four vaccinated mothers and 21 COVID-19 patients havingcomorbidities. Characteristics of the vaccinated and the infected groups are summarized in Table 1.

The median gestational age for vaccination was 29 weeks. The gestational age for COVID-19 infection was 26 weeks on average. The antibodies N and S of mothers and babies differed statistically between vaccinated and COVID-19-infected patients, with the vaccinated group having significantly higher levels of antibody S for both mothers and babies and the COVID-19-infected group having higher levels of antibody N. Transfer ratio of antibody S had a significant difference.

Maternal factors correlation with mothers and cord blood antibodies of vaccinated group and COVID-19-infected group are presented in Table 2. In vaccinated group, mothers and cord blood antibody S had a weak negative correlation with age. Mothers antibody N from COVID-19 infected group had a weak positive correlation with age, all antibodies of COVID-19-infected mothers and cord blood had a moderate negative correlation with gestational age except mothers antibody N.

Correlation between maternal factors and antibodies transfer ratio of the vaccinated and COVID-19-infected groups is represented in Table 3. Transfer ratio of antibodies N and S from COVID-19-recovered patients had a strong negative correlation with gestational age and a positive correlation with the interval, whereas antibody N transfer ratio from the COVID-19 group and anti-S and N of vaccinated group had a significant correlation with gestational age at delivery (Table 3).

The transfer ratio was divided into the following two categories: < 1 and 1. In the vaccinated group, 64.5% had anti-nucleocapsid (anti-N) transfer ratios 1, and 60.5% had anti-spike (anti-S) transfer ratios 1. In the COVID-19-infected group, 50% had an anti-N transfer ratio < 1, and 60.8 % had an anti-Stransfer ratio < 1. Frequencies of transfer ratios < 1 and 1, stratified by maternal factors are shown in Table 4 for the vaccinated group andCOVID-19-infected group.

From vaccinated patients, gestational age at delivery had a statistically significant association with anti-N and anti-S transfer ratios with preterm delivery having a high prevalence with anti-transfer ratios of < 1 and delivery at > 37 weeks having a high prevalence with anti-transfer ratios of 1 (Table 4). Gestational age at delivery from COVID-19-infected patients had a statistically significant association with anti-S transfer ratio with 90% of the preterm delivery having an anti-S transfer ratio < 1. Interval at COVID-19 infection had a statistically significant association with anti-N and anti-S transfer ratios as interval of < 100 days had a high prevalence in anti-transfer ratios of < 1 and interval of > 100 had a high prevalence in anti-transfer ratios of 1 (Table 4).

Difference in the sequelae of both vaccinated and COVID-19-infected preterm, still-born, and preeclampsia babies are represented in Table 5. There were no statistically significant differences between the two groups' sequelae.

Antibody intervals frequency of the vaccinated group from the second dose was highest within 34-44 days and 54-64 days, whereas intervals from COVID-19 infection were highest within 67-97 days (Figures 1, panels A and B).

Mother's and cord blood antibodies N levels peaked 21 days after the second dose and then gradually decreases over time. Both mother's and cord blood antibodies N were at their lowest level starting from 105 days after the second dose (Figure 2, panel A). After 37 days from the second dose, the mother's and cord blood antibodies-S levels were both at their highest level (25000 U/mL). Antibodies S levels were < 1000 U/mL at 56-73 days following the second dose.Except for one vaccinated mother who had an antibody S of (16907 U/mL) after 95 days, both mothers and cord blood antibodies S were at their lowest levels (Figure 2, panel B).

From 46 to 171 days following COVID-19 infection, mothers' and cord blood antibodies N levels varied between 100 and 250 COIlevels (Figure 3, panel A). Antibodies S levels in mothers and cord blood rise to levels above 400 U/mL, starting from 101 days after COVID-19 infection. One mother and cord blood antibodies S were above 700 U/mL, 59 days after the infection (Figure 3, panel B).

Figure 4, panel A, illustrates how the transfer ratios for both mothers and cord blood rise as the number of days since COVID-19 infection increases. The transfer ratios of mothers and cord blood rise as the number of days following the second dose increases, with two patients having high transfer ratios of 10.75 after 21 days and 13.76 after 60 days (Figure 4, panel B).

The COVID-19 pandemic raised several questions about pregnant women, including the impact of infection during pregnancy and transmission of the disease to the newborn. Protection of pregnant women and fetuses against the worst of the disease remains an enormous concern for obstetricians. Immune responses to the infection and vertical transmission of antibodies are accounted for when giving the vaccination during pregnancy. Immunization is optimized for maternal and infant protection. Elements that affect vaccine acceptance are public awareness of infection risk, vaccine safety, and the method of public communication regarding the vaccine and its safety [6]. Our populations were encouraged to get Sinophram and Pfizer.

Group 1 patients' age range was 19-42 years, and group 2patients' age range was 18-42 years. The populations were of reproductive age, and titers varied along with maternal age. Immunity decreased as age increased [7]. Antibody S had a weak negative correlation with maternal age while, surprisingly, antibody N had a positive correlation with age. Individual variations in response to immunization and immunological reactions to COVID-19 infection occurred at the reproductive ages. A similar study by Yang et al. (2021) showed differences in the immune response in different age categories of the general population [8]. Collier et al. found a better response in vaccinated younger people than in older people of the general population [9]. Obesity is a risk factor for COVID-19 and could cause a stronger immune response. Our study grouped titers of antibodies and the transfer ratio and did not find any association with BMI. By contrast, Soffer et al. (2021) identified a relationship between COVID-19 antibodies and obesity in the general population [10]. In our study, four vaccinated mothers and 21 COVID-19 patients hadcomorbidities such as hypothyroidism, gestational diabetes, and bronchial asthma.

A study by Prabhu et al. (2021) found that pregnant women who received mRNA vaccines produced maternal antibodies as early as five days after their first vaccination dose. Notably, passive immunity via the placenta to the neonate occurred as early as 16 days after the first vaccination dose [11]. In our study, the first dose received was at the gestational age of 26 weeks, and the second dose was at 29 weeks. The reported average gestational age at the onset of COVID-19 infection was 26 weeks. An analysis of antibodies was conducted at the time of delivery. The frequency of antibody intervals in the vaccinated group from the second dose was highest from 34 to 44 days and 54 to 64 days whereas intervals from COVID-19 infection were highest between 67 and 97 days. Comparison of antibody titers between the groups showed statistically significant, higher levels of anti-S and vertical transmission in the vaccinated population and anti-N in the infected population. This denotes the higher immunogenic response to the spike protein that occurred in the vaccinated group and the higher immunogenic response to the nucleocapsid protein that occurred in the COVID-19-infected group. Supporting our study, immune responses in the mother and transmission to the fetus of the mRNA vaccines were more elevated in the vaccinated mothers than in the COVID-19-recoveredmothers [12]. A study by Polack et al. (2020)showed that two doses of the BioNTech/Pfizer BNT162b2 mRNA vaccine gave 95% protection against COVID-19 in the non-pregnant age group of 16years or more [13]. In our study, the mean gestational age at vaccination was 29 weeks, and all of the vaccinated population included in our study received two doses of the vaccine. They had protection until the early postpartum period, which supports the use of the vaccine to protect pregnant women from the virus during the pregnancy, which is a more critical period. However, the vaccines long-term protection requires further study. The levels of protection of the COVID-19 group and the vaccinated group remain inconclusive. Nevertheless, vaccinating the pregnant population is important because it reduces the severity and transmission of the disease [14,15]. Vitiello (2021) reported that there was decreased transmission of the virus among the vaccinated population. The level of protection varies after each dose of the vaccine and according to the variant [16]. Supporting this view, our study showed statistically significant levels of anti-S and a higher transfer ratio in the vaccinated population compared with the COVID-19-infected, non-vaccinated population. Vaccination could reduce the rate of COVID-19 infection in pregnant women as well as in neonates.

In our study, the latency period was calculated either from the second dose of the vaccine or from the diagnosis of COVID-19 infection to delivery. The latency period showed statistical significance for both anti-N and anti-S titers and transfer ratios for the COVID-19-infected population. Higher transfer ratios occurred when the interval was greater than 100 days. A study by Mithal et al. demonstrated that vaccinated women had higher transfer ratios of antibodies according to their latency period [17]. Yang et al. showed that the level of vertical transmission of antibodies was elevated at the time of delivery in vaccinated women, regardless of the timing of vaccination [18]. Edlow et al.s study compared the vertical transmission of different types of viral antibodies and reported decreased transfer of SARS-CoV-2 antibodies; thus, COVID-19 infection in neonates and infants from infected mothers was predicted [19]. A study by Flannery et al. showed that an immunological response and vertical transfer of antibodies predicted potential protection against infection in pregnant women and neonates [20]. However, higher maternal levels of anti-S and transfers through placentae following vaccination could provide more protection against the virus. In our study, the transfer ratio of anti-S was calculated at 1.23 (0.68, 1.6) in the vaccinated group and 0.88 (0.68,1.08) in the COVID-19-recovered group. In an exploratory, descriptive, and prospective cohort study, Collier et al. concluded that the COVID-19 mRNA vaccine was immunogenic and evoked antibodies that were transferred to cord blood and breast milk [21]. This is consistent with our study with regard to cord blood transfer. Vaccination (mRNA) during the antenatal period induces a humoral response in the mother, which is transferred to the fetus. This reinforces the advantage of vaccination during pregnancy, a conclusion reached by Beharier et al. [22].

A prospective cohort study by Nir et al. involving 64 parturient, vaccinated women and 11 parturient women who contracted COVID-19 during pregnancy was conducted to identify the transfer ratio of SARS-CoV-2 antibodies from mother to neonate. They found that transferof SARS-CoV-2 antibodies across the placenta occurred more frequently in pregnant women vaccinated with the BNT162b2 mRNA vaccine. This was confirmed by the positive level of antibodies in both maternal serum and cord blood. The vaccine proved to have a double advantage - maternal protection and neonatal humoral immunity [23].

Our study showed potent immune responses and antibody transfer to the fetus in both group 1 and group 2. The antibody transfer ratio showed significant correlation between gestational age and delivery in group 1 whereas group 2 showed a correlation between gestational age and the latency period. The transfer ratio was divided into subcategories according to the levels, either more than one or less than one. Both group 1 and group 2 showed that the level of transfer ratios was higher at a gestational age of more than 37 weeks. Comparable antibody transfer ratios in both groups increased according to the maturity of the fetus. Mithal et al. showed that the COVID-19 mRNA vaccine given during the third trimester generated similar antibody levels between mother and fetus, which were greater in the case of COVID-19 infection [17]. Beharier et al. reported a similar immune response to vaccination and COVID-19 disease and showed that the IgG transfer ratio was higher during the second trimester than the third [22]. The level of transfer ratios was influenced by the birth weight of the infant. In group 1, as the baby's weight decreased, the anti-S transfer ratio decreased as well (a weight of < 2500 g had 75% prevalence of an anti-S transfer ratio < 1).As the baby's weight increased, the anti-S transfer ratio also increased (a weight of > 3500 g had 75% prevalence of an anti-S transfer ratio 1).There was no significant correlation between transfer ratio and the gender of the infant.

Additionally, we compared the incidence of obstetric complications such as fetal growth restriction, preeclampsia, stillbirth, and preterm delivery in the vaccinated group to that of the COVID-19-infected group. Although the frequency of complications was higher in the COVID-19-infected group than in the vaccinated group, no statistical significance was found. The direct relationship between the complications anddisease could not be confirmed. Clinical trials have proven the safety of the vaccine in general; however, trials and data regarding pregnant women are limited [4,24]. Principi et al. reported the safety outline of the vaccine [15]. Shimabukuro et al. revealed that the vaccines side effects are mainly fever, headache, body pain, and chills and recommended more studies focused on perinatal outcomes [25]. Beharier et al. reported the rate of preterm delivery, stillbirth, and preeclampsia in infected pregnant women [12]. No concerning issues were observed by Trostle et al. in pregnant women who received the mRNA COVID-19 vaccine [26]. Peretz et al. deduced that no preterm deliveries occurred among the 57 vaccinated women who delivered [27]. In our study, compared with the vaccinated group, the COVID-19-infected group had a higher rate of preterm delivery (eight vs. 15), stillbirth (zero vs. one), and preeclampsia (two vs. four). Our study illustrated immune responses to vaccination and COVID-19 infection as well as placental transfer of the antibodies. We also included the sequelae of group 1 and group 2 in our study to reassure our pregnant population.

The study of immune responses, vertical transmission, and effects of the COVID-19 infection and vaccination is needed to reduce the impact of COVID-19-related morbidities and mortalities in pregnant women.

During pregnancy, although vaccination and COVID-19 disease produced the immune responses along with the vertical transmission, there was a significant antibody transfer to neonates. A higher response of anti-S and transfer ratio of anti-S occurred in the vaccinated group, which is likely protective for the mother and newborn. Antibody titers varied according to maternal and gestational age. Latency period was significant in the COVID-19-infected population whereas birth weight of the infant was significant in the vaccinated population.

All of our study population developed a reasonable immune response and had vertical transmission. The safety of the vaccine is reassuring and promising for pregnant women.Additionally, vaccinated pregnant women were effectively protected from COVID-19 infection during pregnancy and transferred their antibodies to neonates. Antibody titers varied in different age groups. The transfer ratio was higher in term fetuses. The maternal BMI has no correlation with antibody titers or transfer ratios. The infants gender had no association with transfer ratios.

The reassurance of vaccination without major side effects during pregnancy and protection from COVID-19 helped our pregnant women cope with current modifications in their lifestyles resulting from the COVID-19 pandemic. Even though immunity is helpful in overcoming the current pandemic, further studies of waningantibody levels, reoccurrence of the disease, and duration of protection will support recommendation or refutation of booster vaccine doses.

In our study, vaccinated participants were not infected with COVID-19, and the virus was excluded using nasopharyngeal samples using the polymerase chain reaction (PCR) or SARS-CoV-2 GeneXpert before checking antibody levels. The infected population was not vaccinated either before or during pregnancy. These criteria added clarity to the immune response of the groups. The correlation of antibodies to transfer ratios was calculated in the infected and vaccinated groups in relation to maternal demographic variables such as maternal age, BMI and gestational age, gestational age at delivery, gender of the infant, and birth weight of the infant. Transfer ratios were divided into different ranges, and correlation was calculated considering maternal and clinical factors. Latency period was divided into different ranges, and correlation was calculated considering transfer ratios.

The sample size is small in both the COVID-19-infected and vaccinated groups. Our study did not analyze the post-delivery sequences for the mother and newborn. The waning of antibody levels was not analyzed and requires further study. Categorization of IgG and IgM was not completed in our analysis.

The pregnant women generated anti-N and S in response to COVID-19 infection and vaccination and efficiently transferred these to neonates. The immune response to COVID-19 infection and vaccination was individualized, and titers of anti-N were higher in COVID-19-recovered women. Levels of anti-S and transfer ratios of anti-S were higher in the vaccinated pregnant women. Antibody variations occurred based on maternal age in both groups. BMI showed no association with antibody titers or transfer ratios. Transfer ratios were higher in term babies in both groups and showed no significant relation to the babys gender. A prolonged latency period had a higher transfer ratio in the COVID-19-infected group whereas the birth weight of the infants was significant in the vaccinated pregnant population. However, the level of immunity and duration of protection remain inconclusive. Both COVID-19-recovered and vaccinated women showed an immune response as well as a transfer of antibodies at different rates to neonates. Further studies could include the risk of COVID-19 severity during pregnancy vs. the benefit of vaccination and which group gives more protection to neonates against COVID-19 and future possible variants.

In a recent study posted to the bioRxiv* preprint server, researchers assessed the impact of a syntenin inhibitor on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry.

Viruses depend on interactions with host factors to effectively cause infection and subsequently replicate. Therapeutic approaches that target such interactions enable the development of novel and effective antiviral drugs. Syntenic is an important protein that regulates the architecture of essential cellular membranes due to its role in protein trafficking. Due to this function, syntenin is also shown to have a useful impact against the human papillomavirus (HPV).

In the present study, researchers the usefulness of syntenin inhibitor KSL-128114 as a broad spectrum inhibitor against viral infections, including coronavirus disease 2019 (COVID-19).

The team collected synthetic fluorescein isothiocyanate (FITC)-labeled peptides that corresponded to the C-termini of the viral envelope (E) protein, open reading frame (ORF)-3, and nonstructural protein 11 (NSP11) from SARS-CoV-2. These peptides helped estimate the affinities towards recombinantly expressed and purified PDZ1-PDZ2, SNX27 PDZ, and MPP5 PDZ, respectively.

Additionally, the team investigated the consequences of viral infection and replication via the inhibition of syntenin interactions. This was achieved by penetrating the cells with a peptide-based inhibitor KSL-128114 to estimate the level of SARS-CoV-2 infection as per the concentration of the inhibitor present in Vero E6 cells. Furthermore, the antiviral mechanism of the inhibitor was analyzed by experimenting wherein the time of inhibition addition was assessed. The effect of adding the inhibitor two hours before and one or three hours after the infection was subsequently calculated.

Furthermore, the impact of the inhibitor on the binding of the virus to the host cell or the entry of the virus into the host cell was investigated by treating the host cells with the inhibitor two hours before infection. The team then estimated the level of viral ribonucleic acid (RNA) with quantitative polymerase chain reaction (qPCR) after one hour on ice or two hours of infection. Additionally, infected Vero E6 and Calu-3 cells were treated with chloroquine, and the infection was monitored.

The study findings showed that syntenin PDZ1-2 bound with the highest affinity to the putative PDZ binding motif at the SARS-CoV-2 NSP11 C-terminus. Syntenin PDZ1-2 also showed low binding affinity to the peptide in the viral E protein. The affinities observed were low but similar to those found in endogenous syntenin interactions. The interaction noted with oligomeric E protein could be improved via avidity effects within a cellular setting. Moreover, when MPP5 PDZ was added as a control, it bound preferentially to the viral E protein. On the other hand, SNX27 was bound to all three peptides with comparatively lower affinity.

The peptide-based inhibitor KSL-128114 effectively blocked viral infection with no to minor effects on the viability of the cells. Treatment of the cells with 30 M of the inhibitor showed that viral infection, as well as the number of new viral particles released, reduced significantly. Although treatment with the inhibitor before infection had a remarkable impact on the level of infection, the team observed that post-infected treatment did not result in any effect, which indicated that the inhibitor inhibited the initial steps of viral infection, which take place before the incidence of any interactions between the viral proteins and syntenin.

Interestingly, the antiviral effect of the syntenin inhibitor could not be elicited by inhibiting the interactions between viral PDZ binding motifs and the intracellular PDZ proteins. This was because these interactions occur in the later stages of viral infection. The results indicated that the inhibitor blocked essential endogenous interactions crucial in the initial phases of the viral life cycle, such as the interaction between PDZ and angiotensin-converting enzyme 2 (ACE2) proteins during ACE2 endocytosis and recycling. Testing the affinity of the inhibitor to SNX27 showed that the inhibitor bound with 15 times lower affinity to SNX27 than to syntenin.

The team hypothesized that syntenin PDZ1-2 was likely to bind to the ACE2 terminus and have a direct role in its trafficking. However, syntenin did not display any binding toward ACE2, while treatment of the ACE2 cells with the syntenin inhibitor did not impact the ACE2 expression on the cell surface. Instead, the team observed that inhibitor treatment reduced the expression of syntenin cargo syndecan-1, which suggested that the inhibitor induced the inhibition of syntenin-dependent endocytic trafficking.

The inhibitor did not cause any alteration in SARS-CoV-2 binding in the cells. Furthermore, the concentrations of both negative and positive-stranded single-strand (ss) RNA were reduced, suggesting that viral entry was inhibited. Moreover, viral infection was significantly inhibited in chloroquine-treated infected cells since chloroquine blocked endosomal entry in Vero E6 cells lacking transmembrane serine protease 2 (TMPRSS2) expression.

Overall, the study findings showed that the syntenin inhibitor KSL-128114 inhibited different viral infections, including COVID-19.

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Maybe you know the feeling.

You dodged the initial spring 2020 wave of COVID, but caught the virus during the Delta wave of fall 2021, or the initial Omicron wave the following holidays, or another Omicron spawn more recently. Months later, you find yourself feeling a little tired and foggy.

You could be forgiven for wondering, Do I have long COVID? Is that why Im mentally hazy?

Indeed, brain fog, muscle aches, and fatigue are some of the most common symptoms of the nebulous condition called long COVID, which experts think affects as many as one in five Americans who survived the relatively new virus.

Theyre seemingly mild, compared to the more than 200 other potential symptoms of long COVID, like the development or worsening of cardiac ailments, autoimmune diseases, and neurological issues like a persistent feeling of brain on fire.

Just how likely is it that your new, post-COVID symptoms are long COVID? How long will they last? And whats the difference between a bout of brain fog and a potentially fatal post-COVID complication?

Theyre the questions on the minds of countless patients and doctors right now: Is my new eczema long COVID? Is my worsening diabetic glycemic control due to COVID? I feel kind of mentally foggyam I a long hauler?

Its hard to attribute a symptom to a condition like long COVID when that condition has yet to be clearly defined, experts say.

The trouble is thatfor now, at leastlong COVID can encompass everything from patients who had mild COVID and have lingering mild symptoms, to those who were hospitalized with severe COVID and continue to suffer from resulting organ damage, Dr. Alba Miranda Azola, co-director of the Post-Acute COVID-19 Team Program at Johns Hopkins University School of Medicine, told Fortune.

For those with pre-existing conditions, its impossible to say if such outcomessay, a heart attackare due to COVID, the condition, or a combination of bothand the answer might vary by person. Those who had severe COVID-19 are at greater risk for death in the year following, according to a 2021 study out of Florida that considered more than 13,000 health records. And a study published in March of this year, considering over 150,000 COVID survivors and control groups in the thousands, found that survivors were at a substantially increased risk of heart disease, which could lead to death.

Whats more, some long COVID patients have symptoms that arent related to the condition, or that would have occurred anyway.

As far as how long long COVID symptoms might last, some patients do report improvement and symptoms that resolve completely in a matter of months, experts say.

But countless others have not reported such a resolution. They may eventually recover; its too early to say. Were only two and a half years into the pandemic, Dr. Glen Maysthe chair of the Colorado School of Public Health, as well as a professor theretold Fortune. Society has yet to truly see what the long-term consequences are.

Many who self-report long COVID simply have post viral complications that could happen after many viral and bacterial infections, such as Lyme disease and Epstein-Barr virus, Dr. Panagis Galiatsatos, an assistant professor at Johns Hopkins Division of Pulmonary & Critical Care Medicine, recently told Fortune.

In these cases, it will likely take someone three to six months to get back to normal. Healing from COVID can be a lot like healing from a scraped leg after a fall from a bike, he said.

The initial impact of the scrape is gone, but the scar is going to take time to heal, he said. Patients who are still coughing at two monthsthats part of healing.

Theres no evidence that patients who had mild COVID symptoms and now have relatively mild long COVID symptoms are at an increased risk of mortality, Azola said.

But that doesnt minimize the potential harm of such symptoms. For example, mental haziness could put someone at a greater risk of a car crash or an injury while operating heavy machinery.

Brain fogyou may not think it may immediately or directly result in death, but imagine situations where if youre not able to concentrate, thinkyou may be more likely to have an accident, Dr. Bruce Y. Lee, a professor of health policy and management at the City University of New York School of Public Health, told Fortune.

Those with long COVID who are easily exhausted may not be able to get adequate exercise, which could elevate their risk for chronic diseaselike obesity, high blood pressure, and type 2 diabetesand premature death in the future, Mays said.

And then theres the mental health impact of long COVID that cant be ignored, he pointed out.

Theres an epidemic of mental health problems in the U.S., partially accelerated, directly and indirectly, by the COVID pandemic, Mays said. Thats another pathway where long COVID can have severe adverse effects on health by creating mental health conditions or worsening pre-existing ones.

Long COVID symptoms like depression and anxiety can be deadly, he said, adding that the inability to move like one used to, exercise regularly, and attend work can also lead to a longer pathway toward health decline.

The best advice, experts say, isnt to accept long COVIDor even COVIDas an inevitability, and to take precautions like using face masks and social distancing.

Theres a spectrum of how people get it, Galiatsatos said of the virus, adding that how you catch COVID may determine if you develop long COVID. For instance, those who vaccinate and/or treat their infection with antiviral Paxlovid may be at lower risk of developing the condition, some studies suggest.

Statistics like the CDCs assertion that one in five U.S. adults whove had COVID have long COVID are generally based on surveys, with individuals self-identifying and not necessarily having been formally diagnosed.

Such questionnaires are basically asking, Do you have any new health problems since youve had COVID? Dr. Alexandra Brugler Yonts, an infectious disease specialist who runs a long COVID clinic at Childrens National Hospital in Washington, D.C., recently told Fortune.

Which is a challenge, because life still goes on, and people still develop health conditions.

The takeaway: Now is not the time to throw your hands in the air and caution to the wind. COVID can be avoidedat least sometimeslong COVID isnt inevitable.

Said Brugler Yonts: Just because Im probably going to get flu at another point in my life doesnt mean I lick subway rails.

As the world continues to learn how to live with Covid-19 in the long run, scientists are testing ways to quickly tell people how well-protected they are against the virus, and whether they need another booster.

A new study, published Monday in Cell Reports Methods, presents a simple test to detect neutralizing antibodies against SARS-CoV-2, using little more than a finger prick and a testing cartridge. The approach, if it bears out in large-scale testing and receives the blessing of regulatory agencies, could one day offer a cheap, easy option to measure protection against the virus.

People want to know, Am I protected today? And there isnt a tool on the market that can facilitate that answer, said Charles Mace, a chemist at Tufts University who was not involved in the new study. This has that potential.

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Antibodies float around in the bloodstream, waiting for a foreign invader to make it in. When a virus does, some antibodies that are specific for parts of the virus neutralizing antibodies recognize and bind to it, which marks the virus for destruction and prevents it from infecting any cells. The body can naturally develop neutralizing antibodies through exposure to the virus after vaccination or an infection.

When scientists want to determine whether those neutralizing antibodies are present in a person, they take blood samples, separate out the serum, and mix it with live SARS-CoV-2 virus. They then incubate that mixture with a human cell line and see how many of those cells die off. Scientists can also use other viruses that have been engineered to make the spike protein and a fluorescent molecule. But both of those methods require live virus, which means training and a biosafety lab, and take about 2 days to run.

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Researchers have been developing other, faster methods. But by and large, they either require laboratory equipment or are more complicated to manufacture because they use antibodies.

The project started when Hojun Li, a hematologist and investigator at the Koch Institute, saw a bone marrow transplant patient at the Dana-Farber Cancer Institute right around the time that the pandemic hit the U.S. hard. But before the operation, they presented with symptoms for Covid-19. At the time, the only option available for doctors to rule out a Covid-19 infection was to do a blood test and examine the antibody levels. It took a week for the results to come back negative and Li to be able to proceed with the bone marrow transplant. These are usually very urgent, urgent things to do, Li said. The longer you wait, the more likely whatever underlying diseases that come back cannot be cured by the bone marrow transplant.

Li and his colleague at the time, Guinevere Connelly, started talking about how they could close that knowledge gap with Covid. Connelly, a co-first author of the study and now a Ph.D. student at Duke University, said they quickly realized that what would be really helpful would be a neutralizing antibody test where you could see what level of protection you may have against infection from Covid or from SARS-CoV-2.

With collaborators, they learned new techniques to make every component of a test, from producing viral proteins at a larger-scale to cycling through a hundred different buffer formulas. It took them a year to collect enough test samples repeat blood draws from two people before and after vaccination, and single donations from 93 other individuals to design and validate the test.

The result of their work is a device that looks and works like existing rapid antigen tests, which detect protein from the virus when someone is actively infected.

The new test uses a small amount of blood, obtained via a finger prick, that gets mixed with a buffer that contains the portion of the SARS-CoV-2 spike protein that binds to the ACE2 receptor on human cells. Where a typical antigen test has two binding sites a control line that shows the test is working properly and a test line that lights up when a person is positive for the coronavirus the new one has three: a control line, a line turns an intense red when a person does not have neutralizing antibodies, and a line that appears when they do.

We also like people to think about positive signals as opposed to reduction of signals because theres just a general feeling that thats more reliable, said Angela Koehler, a bioengineer at MIT who worked on the new test. Indicating both the presence and absence of neutralizing antibodies, the researchers said, allows everyday consumers to snap a picture with their mobile app to know their quantitative antibody titer.

If you have an actual number that you can measure and neutralizing antibody concentration would be a number that you can actually measure then you can tell what degree of protection they have and whether or not they might need a subsequent [dose] or a booster sooner rather than later, said Li. That kind of information could be of interest to a wide range of people, but would be particularly helpful for those who have weaker immune responses, like those Li sees in the clinic. The vast, vast majority of patients I see get bone marrow transplants, he added. Their immune system is just really wiped out.

Basing booster decisions on antibody levels is not too far-fetched an idea. In Australia, for example, antibody testing is used to determine if someone needs a 4th dose of the hepatitis B vaccine.

But Julio Delgado, the clinical pathology chief at the University of Utah School of Medicine, is more skeptical that the new test will find use among the broader population. Even if I get vaccinated, Im still going to get infected at some point. That happened to me, said Delgado, who has developed laboratory-based clinical tests that measure levels of antibodies against SARS-CoV-2. So the understanding about neutralizing antibodies has really become more of a scientific interest, not necessarily a clinical utility.

Some experts said that any use case was overly optimistic because we dont yet know what antibody levels translate to optimal protection. This is complicated by the fact that different assays calculate titer levels differently. There is not an understanding about thresholds above or below which people are going to be prone to getting infected, or prone to develop progressive disease, or prone to die, said Delgado. Yes, you get a number, but what does that mean?

In part because the new test can be manufactured for less than a dollar a kit, its developers said that is exactly one of the questions their new product can answer. Its really the first one that Ive seen that can answer that question, said Hadley Sikes, a chemical engineer at MIT who was a senior author of the research. If there was a study design where you use this tool you recruit a cohort, say, 5,000 or 10,000 people, you get these neutralizing antibody tests in their homes, and you follow who gets infected and doesnt get infected its an answer to a question that a lot of people, a lot of doctors, a lot of articles in the press have been raising.

The team behind the test saidthey areinterested in pursuing an emergency use authorization down the roadand would want to work with an industry partner or foundation that has experience with regulatory applications.

But Li acknowledged that the Food and Drug Administration has a little bit of hesitancy about anything antibody-related, but attributed this to tests that measured all antibodies, rather than only SARS-CoV-2 neutralizing antibodies. A lot of those tests flooded the market and a lot of them, frankly, were very, very poorly managed, he said. Because antibody levels decline gradually, testing once a month would likely be enough. On the flip side, though, such infrequent testing needs might make it less appealing for commercial players to invest in the studies that would be needed to move the tests from a proof-of-concept to an authorized product.

A different approach on the horizon uses a costlier machine called a spectrometer to detect the Covid-fighting antibodies. Cheng-Hao Ko, an engineer at the National Taiwan University of Science and Technology, said this would be 300 to 400 times more accurate than the rapid test approach. Ko is collaborating with a group at Temple University to seek emergency use authorization from the FDA for that device.

That level of accuracy likely wouldnt be necessary for the general public. If you have a good indication of low, mid-range, and high level of antibodies, thats probably good enough for the purpose, said Jean-Franois Masson, a biochemist at the Universit de Montral in Canada.

Adolfo Garcia-Sastre, a virologist at the Icahn School of Medicine at Mount Sinai, said theres also a potential to use this type of test as a tool to understand immunity at the population level and help guide public health decisions, for example by routinely testing samples from blood donors. Surveillance is going to become more important, I hope, in the next year, he said, because it gives you an idea of what is the vulnerability.

Coronavirus disease 2019 (COVID-19) has affected almost every dimension of human life, ranging from health to social, psychological, economic, and financial domains [1]. The world was soon disrupted by the emergence of COVID-19, with the hardest hit countries, such as America and Europe, reporting the highest death count of 178,378 deaths [2]. Because the virus was new and of unknown etiology, governments across the world enforced travel restrictions to and from China [3].

Governments across the world imposed a complete lockdown on their entire population (20% of the global population) with the closureof public places and transport, isolation of suspected cases, and establishment of quarantine centers [4]. In India, after the successful control of the first wave of COVID-19, the government granted relaxation in interventions. Due to this relaxation, along with negligent public behavior and the mutant strain (B.1.1.617) that emerged, the second wave created havoc with 0.2 million cases [5,6].

Government agencies were unable to understand the behavior of people during the pandemic.A national action plan for COVID-19 was devised by the Ministry of Health with the aim of effective preparedness and efficient response by ensuring all safeguards were in place to prevent an outbreak of COVID-19. The identification and activation of available financial and other resources to ensure maximum preparedness and response, provision of supplies, and infection prevention and control in healthcare settings were also a part of this plan [7]. New strategies were devised to implementhealth measures for travelers and strengthen readiness capacity to rapidly identify, diagnose, and treat cases, including identifying contacts with tracing and follow-up, as well as minimizing the community spread of the virus in Pakistan. Quarantine centers were established in the urban centers of Pakistanwith the help of Pakistansarmed forces, and a robust surveillance system was developed throughout Pakistan [3].

The lockdown became a great threat to the economic and financial stability of the country. Policy frameworks were drafted in an attempt to prevent, detect, and respond immediately to confirmed cases by federal and provincial governments [8]. A vast majority of the people believe that their government and the countrys citizens are not doing enough and underestimate the degree to which others in their country support strong behavioral and policy responses to the pandemic. The lack of satisfaction with government policies is associated with higher levels of worry among the public and the resultant fall in the publics compliance rate [9].

The rationale of this survey is to focus on the current state of the COVID-19 pandemic in Pakistan by addressing the limitations and challenges in emergency preparedness and critically reviewing the results of the plan of action devised by the government of Pakistan. The willingness to cooperate and adopt health-protective behaviors during pandemics can only be truly predicted by measuring the publics reaction to the crisis and coping strategies.

This study was conducted among the general population living in and around Lahore as an online survey. The study was conducted from April 2021 to September 2021.A descriptive, cross-sectional study design was used for this study.Informed consent was obtained from all study participants.

Asample size of 200 was calculated with the help of the World Health Organizations (WHO) sample size calculator by maintaining a 95% confidence level and a 5% margin of error. A non-probabilistic convenience sampling technique was used for data collection. A self-administered questionnaire was designed using Google Forms.It was distributed through social media platforms and direct email solicitation.Questionnaires were distributed among national groups created on social media to spread COVID-19 information and concerns. Only people over the age of 18 and those who could read and understand English and could fill outthe mediumsonline were included in the study sample. Those under the age of 18 and who were not willing to participate were excluded from the study.

We conducted a detailed literature review to draft a questionnaire. The draft questionnaire was pilot tested among 25 participants (the results of which were excluded from the study) and was sent to multiple senior researchers for evaluation, incorporating all appropriate recommendations into the questionnaire. Informed consent was obtained and kept confidential, and no personally identifiable information was collected or stored. The structured questionnairewas finalized and consisted of 33 questions.

The questionnaire mainly included the following aspects: (1) a brief description of the study and informed consent; (2) demographic variables such as age, gender, education level, area of residence, family income, and occupation; (3) perception and beliefs of the public regarding the COVID-19 pandemic; (4) perspectives of the governments response to cope with the pandemic and testing strategy; (5) awareness and willingness to wear masks and social distancing; (6) perceptions of lockdown strategies; (7) closures of educational institutes and public centers; (8) sources of communication and media regarding COVID-19; (9) perception and beliefs of the public about the governments vaccination program; (10) diagnostic and testing facilities; and (11) perceptions of the governments strategy to meet healthcare needs by capacity enhancement of public hospitals and involvement of the private healthcare system.

The collected data were entered, coded, and analyzed using SPSS version 23 (IBM Corp., Armonk, NY, USA). The results were assessed using descriptive statistics, and means with their standard deviation (SD) were presented for continuous variables such as age.Categorical variables were reported as frequencies and percentages.Data are presented in the form of frequency tables, bar charts, and pie charts.Quantitative variables are presented as means and SDs.

This study included a total of 200 participants, of whom 46% (n = 92) were males and 54% (n = 108) were females. The mean age of the study population was 25.83 years. Approximately 91% (n = 183) of the study participantswere aged between 18 and 30 years. The study population comprised predominantly people living in densely populated urban areas (51.5%; n = 103), and 48.5% were from large urban centers (n = 97). Over half of the participants were doctors by profession (n = 102), 5% were teachers, 4.5% were office workers, 3% were businesspersons, and 73 (36.5%) belonged to other professions. The majority of study participants were graduates (70%; n = 140). Overall, 40% of the respondents had a family income greater than PKR 100,000 per month. The demographics and characteristics of the participants and individual p-values are presented in Table1.

A large segment of our study population was found to be well aware of the existence of COVID-19 as a pandemic (74%; n = 148) and found it to be a major problem for the community (7%; n = 14) who perceived it as a biological weapon, whereas 5.5% considered it as an international conspiracy, and others professed it as a highly infectious disease (n = 27). The results are shown in Figure 1.

Of the 200 respondents, 71.5% (n = 143) were satisfied with the governments policies, and 28.5% (n = 57) were not satisfied. A total of 66.5% (n = 133) of participants agreed that government policies were effective, and 33.5% (n = 67) did not agree that the policies were effective in combating the virus. More than half (80%; n = 160) of the respondents thought that government policies had reduced the rate of COVID-19 spread, while 20% (n = 40) thought that the policies had not reduced the rate of spread.

Only 16.5% (n = 33) of the respondents thought that the lockdown policies were not effective against COVID-19. More than half (65%; n = 130) of the respondents thought that smart lockdown was better than complete lockdown, while 35% favored complete lockdown. Of the 200 respondents, 97% (n = 195) agreed with the governments decision to make wearing masks and social distancing mandatory, while only five (2.5%) respondents did not agree with the decision. Overall, 91% of the respondents believed that wearing masks helped them escape COVID-19, while 9% believed that wearing masks did not help them. A total of 79.5% (n = 159) of the respondents favored the governments decision to impose restrictions on public transportation, while 20.5% (n = 41) opposed it. Moreover, 81% of the participants were satisfied with the traveling restrictions placed by the government to manage COVID-19, while 19% were not satisfied. More than half (n = 160) of the participants believed that government guidelines for educational institutions were effective, whereas 20% did not agree.

Of the 200 respondents, 62.5% (n = 125) agreed with the governments decision to close educational institutions and instituting online classes, while 37.5% (n = 75) disagreed with this decision.

Approximately half (56%; n = 108) of the participants believed that the governments decision to strictly impose standard operating procedures (SOPs) on the general public was effective. More than half (87%) of the respondents thought that the government was effectively providing health education messages to the public through the media, whereas 13% were not satisfied. Moreover, 96% of the respondents believed that quarantine was a good step taken by the government to prevent COVID-19.

Of the 200 participants, 97.5% agreed that the governments vaccination program was a good step toward managing COVID-19. A total of 178 (89%) participants thought that the government should make vaccination mandatory for all, and 11% thought that it should not be mandatory for all. More than half of the participants (93.5%; n = 187) believed that the government should invest more in Pakistan regarding vaccines instead of importing them from abroad, while 6.5% (n = 13) thought that the government should buy foreign vaccines. Overall, 96%(n = 192) of the respondents agreed that everyone should be vaccinated free of cost.

Of the 200 respondents, 95.5% (n = 191) agreed that it was a good step taken by the government to test the family members or contacts of a COVID-19-positive case for screening, while 4.5% (n = 9) disagreed. A total of 194 (97%)respondents thought that freepolymerase chain reaction (PCR) testing by the government was a good decision. More than half (76%; n = 152) of the 200 respondents believed that the governments diagnostic capacity and home testing services had improved, while 24% (n = 48) believed that the services needed to be improved. Overall, 63% (n = 126) of the respondents believed that the government had increased its healthcare capacity, while 37% (n = 74) were not satisfied. Moreover, 83 (41.5%) thought that the government hospitals were capable of carrying the COVID-19 load, while more than half (58.5%; n = 117) thought that the hospitals could not carry the load. Out of the 200 respondents, 95.5% (n = 191) agreed that the government should collaborate with the private sector, while 4.5% (n = 9) disagreed.

Table 2 describes all the questions asked from the participants regarding their perspectives on the governments policies in combating the COVID-19 pandemic.

COVID-19 is a serious public health emergency with severe adverse implications for the population, healthcare systems, and economies globally [10]. Centralized and professional leadership, democratic and accountable political culture, liberated civil society, and broad social participation are the key features of disease control in a country [11].

The results highlight the broader impact of the COVID-19 pandemic on the publics overall health and well-being, outsidepersonal infection, and their satisfaction regarding governmental policies in combating the coronavirus infection [12].

This study was conducted to determine peoples perspectives regarding government policies to combat the COVID-19 pandemic. In this study, out of the 200 respondents, 14 (7%) thought of it as a global pandemic, 148 (74%) thought of it as a biological weapon, 27 (13.5%) thought of it as a highly infectious disease, and 11 (5.5%) thought of it as an international conspiracy. In Bangladesh, out of 240 respondents, 290 (85%) thought COVID-19 was a global pandemic [13].

In our study, around one-third of the participants were not satisfied with government policies to combat COVID-19, whereas a large majority were satisfied. In another survey, out of 200 people, 110 (55%) responded that the government was not reacting sufficiently, 50 (25%) did not trust their government policies, and 40 (20%) were satisfied with government policies [14]. In the current study,160 (80%) thought that the government policies had reduced the rate of coronavirus infection, and 40 (20%) thought that government policies were not effective in reducing the rate of COVID-19 infection. In another survey in the UK, the data were collected from several interventions in 41 countries, out of which 77% of the respondents agreed with the reduction of COVID-19 infection and decreased mortality rate due to policies developed by their government [15].

Out of 167 respondents who favored lockdown, 130 (77.9%) thought that smart lockdown was better than complete lockdown, and 37 (22.1%) thought that complete lockdown was better. In another study in Italy, out of 100,000 respondents, 30,000 (30%) thought that the complete lockdown was a better option, while 70,000 (70%) considered smart lockdown to be a better option [16]. In this study, out of the 200 respondents, 195 (97.5%) agreed with the governments decision to wear masks and social distancing mandatory, while five (2.5%) disagreed with the decision.

In this survey, out of the 200 respondents, 182 (91%) believed that wearing masks helped them escape COVID-19; however, 18 (9%) believed that wearing masks did not help them. In Singapore, 32.5% of doctors, 48.7% of nurses, and 77% of administrative personnel thought that a simple mouth-to-nose protection mask would be sufficient to prevent infection [17]. Out of the 200 respondents, 159 (79.5%) favored the governments decision to impose restrictions on public transportation, while 41 (20.5%) opposed it. However, in another survey in Poland, 90% resigned or limited their usage of public transportation based on precautions imposed by the government [18].

Out of the 200 respondents, 185 (92.5%) agreed with government policies to put restrictions on public places, markets, and social gatherings to prevent COVID-19, while 15 (7.5%) did not agree. In the United States, 74-83% of the decline in foot traffic was due to the formal restriction of social gatherings [19]. Therefore, communities should continue to discourage large gatherings, identify and test social contacts, and isolate confirmed cases to help control the COVID-19 pandemic.

In this study, out of the 200 respondents, 125 (62.5%) agreed with the governments decision to close educational institutions and online classes, and 75 (37.5%) disagreed with the decision. However, in another study in Indonesia, out of 66 participants, 62 (93.9%) students were involved in online classes, and only four (6.1%) had problems joining the online sessions [20]. Out of the 200 respondents, 150 (75%) believed that SOPs set by the government for markets and public places were effective in combating the disease, and 50 (25%) believed that SOPs were not effective.

Out of the 200 participants, 108 (56%) thought that the government strictly imposed SOPs on the public, while 92 (44%) did not agree. In another study in the UK, out of 300 respondents, 210 (70%) thought that the government was strictly imposing SOPs, while 90 (30%) did not agree [21]. Out of the 200 people, 195 (97.5%) agreed that vaccination programs were a good step, and five (2.5%) did not agree, while in Australia, out of 1,420, 1,143 (80%) agreed that getting themselves vaccinated for COVID-19 would be a good way to protect themselves against COVID-19, while 277 (20%) were unaware [22].

In thissurvey, out of the 200 people, 178 (89%) said that vaccination should be mandatory, while 22 (11%) did not like the idea. In another survey held in Australia, out of 1,420 respondents, 355 (25%) self-reported chronic diseased people, and 820 (58%) private health insurance agreed to have mandatory vaccinations for everyone [22]. In this survey, 187 (93.5%) people thought the government should invest more in Pakistan regarding vaccination, and 13 (6.5%) said the government should buy foreign vaccines. Out of the 200 respondents, 192 (96%) agreed that the government should vaccinate everyone free of cost, while eight (4%) disagreed. In another survey in India, out of 1,000 respondents, 840 (84%) reacted in a positive tone, and 160 (16%) answered in a negative tone [23].

In this study, 191 (95.5%) said that it is a good step to test the family members of the patients with a positive COVID-19 test, while nine (4.5%) did not agree. Out of the 200 respondents, 194 (97%) said that performing PCR tests free of cost was a good step, while six (3%) did not consider it good. In another survey in Oxford (UK), 96% considered the free PCR test to be a good initiative. In this study, out of the 200 respondents, 152 (76%) agreed that the government had improved the diagnostic capacity and home testing services, while 48 (24%) disagreed. In another study in Bangladesh, out of 1,066 respondents, 875 (82%) strongly agreed, 123 (12.4%) agreed, 40 (3.1%) neither agreed nor disagreed, eight (0.9%) disagreed, and 20 (1.6%) strongly disagreed [24].

Out of the 200 respondents, 192 (96%) considered quarantine a good step for the effective prevention of COVID-19 infection, while eight (4%) disagreed. In Jordan, of 5,057 participants, 4,800 (95%) perceived the benefits of home quarantine [25]. In this survey of 200 people, 126 (63%) agreed that the government had increased healthcare capacity, while 74 (37%) disagreed. In Bangladesh, out of 1,066 respondents, 800 (75.4%) agreed, while 266 (24.6%) disagreed that their government had increased healthcare capacity [24]. During the current COVID-19 pandemic, hospitals have reported a breakdown of services when the surge of patients in need of treatment and ventilator support outpaced available capacities. Out of the 200 respondents, 83 (41.5%) agreed that government hospitals have sufficient healthcare services to handle the COVID-19 load, while 117 (58.5%) disagreed. In the UK, 75% agreed to have sufficient healthcare facilities [26].

Out of the 200 people, 191 (95.5%) agreed that the government should collaborate with the private sector, while nine (4.5%) disagreed, while in another survey in Norway, citizens satisfaction with democracy and their collaboration with the private sector increased from 57% to 72%, which was a very high rating internationally [27]. In this survey, out of the 200 respondents, 162 (81%) were satisfied with the travel restrictions by the government for better handling of COVID-19, while 38 (19%) were not satisfied. In another survey in Paris, out of 1,010 respondents, 470 (46.6%) completely agreed, 240 (23.6%) partially agreed, 130 (12.2%) neither agreed nor disagreed, 80 (8%) partially disagreed, and 80 (7.5%) completely disagreed with the travel restrictions imposed by the government to halt the spread of infection [28].

Like every study, our study also had some limitations. First, due to a strict lockdown, the studyquestionnaire was distributed via online platforms, including social media. Internet penetration varies with agegroups, income level, and educational status. Also, as students of medicine, we had a higher reach to the healthcare community on our social media platforms compared to non-healthcare professionals. Therefore, this could be a challenge in depicting the results, especially when the perception of government policies could also vary widely among these different groups, as mentioned in Table 1. However, the latter point can also provide a better opportunity in understanding the concerns of the public across the occupational strata and especially involving the segment of the society which was affected way more than the rest of the professionals. Second, our sample size of 200 also presents a challenge to adequately predict the public perception at large and difficult to generalize the results to the whole country.

However, we consider that our study has been successful in addressing the specific concerns that the policymakers would face in the future when developing long-term strategies, keeping in mind the perspective and, more importantly, the acceptance of the public. This study also provides a road map, in light of which morestudies can be conducted with larger sample sizes and different segments ofsociety.

The current global economic and health situation is a point of concern for the general population with fragile health systems and low-quality healthcare services.A vast majorityof the public was satisfied with the government policies developed to cope with the COVID-19 pandemic. However, a large proportion was not satisfied with the management of the resources, including materials, equipment, information, and human resource. Moreover, a large section of the public expressed dissatisfaction with the effectiveness of the governments policies, particularly the closure of educational institutes and public places.

This reinforces the need to take measures and address pandemic preparedness by developing more strategic policies to cater to the resurge of such catastrophes in the future. These comprehensive findings can help in developing an emergency and a long-term plan at the national level onpandemic education, managing resources, ensuring hospital preparedness, addressing the rumors and conspiracy theories, and improving the overall healthcare system that can counter the impact of large-scale epidemics.With the ever-changing environment we are living in, COVID-19 has precluded yet more challenges, the latest in the form of monkeypox, more strategic policies need to be included in the future. Therefore, this study takes a more significant spot in shaping public health policiesas long-term objectives can only be achieved with better public participation. Further studies in Pakistan can yield a holistic conclusion on the overall knowledge levels and perceptions of the different segments of the society toward government policies.

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In a recent study posted to themedRxiv* preprint server, researchers analyzed the efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fourth-dose vaccination relative to no vaccination towards the Omicron BA.1 variant.

Global coronavirus disease 2019 (COVID-19) prevention strategies have been hampered significantly by the waning SARS-CoV-2 vaccine effectiveness (VE) and the ability of the SARS-CoV-2 Omicron variant to escape pre-existent immunity. Several nations have launched fourth-dose COVID-19 vaccination programs in response to this.

Relative VE (rVE) towards Omicron following the latest messenger ribonucleic acid (mRNA)-based fourth dose vaccinationversus a third shot given around four months earlier has been documented in published trials in people aged 60 years or older. Interestingly, just one study reported VE of the fourth dosecompared to no vaccination, which the present study's authors refer to as absolute VE (aVE). Nevertheless, third and fourth-dose aVE for equivalent time durations is unavailable.

In the current work, the researchers sought to determine the three-dose and four-dose SARS-CoV-2 vaccine series aVE at the same point after vaccination. They calculated the aVE for the third and fourth doses of COVID-19 mRNA vaccine compared to receiving no vaccination towards Omicron, considering clinical outcome utilizing aset of logistic regression equations and VE estimations for a fourth dosage compared to a third dose described in an Israeli investigation.

Based on information from the United Kingdom Health Security Agency (UKHSA), the authors previously released a logistic regression equation that forecasts aVE, including waning with time, for the third COVID-19 mRNA vaccine dose irrespective of the initial course, against symptomatic infection and hospitalization associated with Omicron. Further, they used a study that reported VE per age against the SARS-CoV-2 Delta variant to expand this equation to account for age variability in VE.

Moreover, the team included the other outcomes of symptomatic and asymptomatic infection, as well as death, leveraging information provided by the UKHSA, to develop a set of equations that estimates the VE of the third dose against Omicron BA.1 variant according to age, the severity of the illness, and the time post-vaccination. Subsequently, they adapted these equations to approximate the aVE of the third dose three weeks aftervaccination. The authors transformed Magen et al.' documented fourth dose rVE to fourth dose aVE estimates three weeks post-vaccination presuming a median gap of 20 weeks between the third and fourth vaccine doses in the Magen et al. research.

Furthermore, the expected aVE readings and their unpredictability intervals were calculated with 10,000 repetitions of Monte Carlo simulation, reproducing uncertainty in the observed rVE of the fourth dose and the scientists' logistic equation estimations of a third dose aVE.

The following are the limitations of the study's approach.

1) The investigators extrapolated UKHSA information onto Israeli information under the assumption that a third shot of the vaccine in Israel would have the same waning effect as one in the UK. Nonetheless, considering the lack of experiments that directly compare persons getting the third and fourth doses at the same timeframe, each matched to those with no previous infection or vaccination, these hypotheses seem acceptable. Besides, it was challenging to envision a substitute technique to assess aVE.

2) The current estimates were based on the VE against the Omicron BA.1 subvariant. Immune evasion may result in decreased fourth dose aVE towards newer SARS-CoV-2 subvariants. Yet, the researchers anticipate that the trends they predict of restored or even slightly heightened aVE post a fourth shot will likely retain.

The research findings suggested that aVE after a fourth dose COVID-19 mRNA vaccination schedule was higher and associated with more severe clinical outcomes similar to a three-dose. The team discovered that a fourth dose of the SARS-CoV-2 mRNA vaccine reinstates or even improves the protection provided by a third dose within the same timeframe following vaccination.

For symptomatic SARS-CoV-2 infection and any infection at the same period post-vaccination, estimated aVE after a fourth dose seems greater than followingthe third dose, albeit uncertainty intervals coincided. In addition, the authors anticipated that policymakers assessing the costs and advantages of the fourth SARS-CoV-2 vaccine doses would be interested in the present estimations.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

In a recent paper published in themedRxiv* preprint server, researchers monitored the safety of the four diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines approved by the European Medicines Agency (EMA) and Medicines and Healthcare products Regulatory Agency (MHRA) in 2020 to 2021.

The widespread and quick transmission of coronavirus disease 2019 (COVID-19) induced by SARS-CoV-2 sparked the necessity for vaccine development to combat this pandemic. In addition, global COVID-19 vaccine development has been spurred by the 11 January 2020 publication of the SARS-CoV-2 genetic sequence.

Less than a year after the genetic sequence's discovery, the first SARS-CoV-2 vaccine emergency authorizations were granted, setting a record for the world's rapid vaccination program. Five distinct COVID-19 vaccines, including Nuvaxovid (Novavax, December 2021), Janssen (March 2021), Spikevax (Moderna, February 2021), Vaxzevria (AstraZeneca, January 2021), and Comirnaty (Pfizer/BioNTech, December 2020), have received conditional authorization in Europe. However, multiple concerns surfaced regarding the risks and advantages of the vaccines at the population and individual levels due to the quick advancement of novel COVID-19 vaccines.

In the current retrospective cohort research, the scientists report on the group surveillance of adverse events of special interest (AESIs) leveraging fourelectronic health care information following the protocol publicly disclosed in the European Union post-authorization study (EU PAS) register. The team tracked the SARS-CoV-2 vaccine use and the occurrence of pre-specified AESI associated with these vaccines before and following vaccination. Besides, the purpose of the study was not to examine a particular hypothesis.

Subjects were enrolled in the study from 1 January 2020 to 31 October 2021, or until the most recent data were available. The Netherlands, Italy, Spain, and the United Kingdom (UK) were the four European nations from whom the team obtained primary or secondary health care information.

Further, the study volunteers were people who had complete information for the year before enrollment in the study or who were born at the beginning of the observation period. There were 25,720,158 people in the study population. Initial and second doses of COVID-19 vaccines from AstraZeneca, Pfizer, Janssen, or Moderna were used as research interventions.

The primary study outcome metrics were 29 AESIs. These AESIs were: acute coronary artery disease, acute aseptic arthritis, acute disseminated encephalomyelitis (ADEM), acute liver injury, acute renal injury, anaphylaxis, acute respiratory distress syndrome, ageusia or anosmia, arrhythmia, chilblain-like lesions, Bells palsy, death, erythema multiforme, generalized convulsion, Guillain Barre Syndrome (GBS), hemorrhagic stroke, ischemic stroke, heart failure, meningoencephalitis, microangiopathy, pericarditis, multisystem inflammatory syndrome, myocarditis, single organ cutaneous vasculitis (SOCV), narcolepsy, stress cardiomyopathy, thrombotic thrombocytopenia syndrome (TTS), thrombocytopenia, and venous thromboembolism (VTE).

The study results indicated that 12,117,458participants had at least one SARS-CoV-2 vaccine dose: 6% with Spikevax (Moderna), 54% with Comirnaty (Pfizer), 2% with Janssen, and 38% with Vaxzevria (AstraZeneca) vaccines. The authors noted that AESIs were very unusual: less than 10 per 100,000 person-years (PY) in 2020, and only cardiac and thrombotic events were uncommon.

Following controlling for variables linked with severe SARS-CoV-2 infection, 10 statically relevant connections of aggregated incidence rate ratios endured based on doses 1 and 2 joined. These AESIs included TTS following both the Janssen and AstraZeneca vaccines, anaphylaxis post-AstraZeneca vaccine, GBS post-Janssen vaccine, erythema multiforme post-Moderna vaccine, thrombocytopenia following the Janssen and Moderna vaccines, SOCV post-Janssen vaccine, and VTE following the Pfizer and Moderna vaccines. Additionally, the aggregated rate ratio was only increased by over two-fold for SOCV, TTS, and thrombocytopenia.

On the whole, the present study demonstrated that using common analytics, the Conception common data model, and an agile method for semantic unification throughout various illnessdiagnosis vocabularies, researchers can track a significant number of AESI among four data sources across four nations. Data were subsequently disclosed with the EMA regularly via an interactive panel.

The study findings revealed associations of COVID-19 vaccinations with various AESI, which persisted even after adjusting for variables affecting vaccine deployment. Numerous (important) rate increases were noticed. Most were addressed already in regulatory discussions, like neurological events, erythema multiforme, and hematological events.

Further, since the current study was not intended for causal inference, the team advised that hypothesis screening analyses would be requiredto assess the excess risk appropriately with adequate regulation for risk variables for the outcomes. Moreover, despite the substantial number of vaccine recipients participating in the research, the power was restricted for the infrequent incidents (10/100,000 PY). Furthermore, ongoing surveillance and upgrading were needed to monitor this accurately or evaluate hypotheses.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

RALEIGH, N.C. (WNCN) Are more fully vaccinated people dying of COVID-19 these days than unvaccinated people?

Thats what a new chart making the rounds on social media appears to show.

But its easy to misinterpret what its actually telling you.

Its based on CDC data at the national level and plots the number of COVID-19 deaths each week by people who are either fully vaccinated or unvaccinated.

It shows that, for the past few months, more fully vaccinated people have in fact died of COVID than have unvaccinated people which is noted by the black (vaccinated) line moving higher than the blue (unvaccinated) one at some unspecified point after February.

But Dr. David Weber, an infectious disease specialist at the University of North Carolina School of Medicine, says that chart is missing one very important piece of information and context: Age.

Most of the cases were seeing now of deaths many of them are in older people, Weber said. The majority of older people, in particular because of their risks for COVID are vaccinated. So its not surprising if the majority of people are vaccinated. Even if the vaccines are working, the majority of deaths will be in people who are vaccinated.

Thats why at the state level, the comparison in the North Carolina Department of Health and Human Services weekly report includes a key phrase age-adjusted.

The real question is not what percentage of deaths or hospitalization are in vaccinated or an unvaccinated? Weber said. Its by age. Whats the risk of death in vaccinated versus unvaccinated individuals?

Taking that into account, the death rate for unvaccinated people remains significantly higher than it is for vaccinated and for boosted, once those figures are adjusted for age.

According to NCDHHS, unvaccinated people in mid-to-late July and early August were nearly 10 times more likely to die of COVID-19 than boosted people were.

Its also important to keep in mind that the chart compares the unvaccinated with the fully vaccinated but makes no mention of those who have received booster shots.

Those who received both doses of the primary series a year ago or more are most likely dealing with a drop in immunity that a booster shot can fix, Weber says.

And it could only be a matter of weeks before new booster shots that specifically target the omicron subvariants could be available welcome news for people who received their first booster shot but so far are not yet eligible for a second one.

So thats really the question that you need to ask is, vaccinated versus unvaccinated? What age group? And then, did you have two, three or four doses? Weber said.

Vaccine opponents have latched onto the chart as evidence that the shots dont work.

Weber says its incredibly easy to misread that chart and come to the wrong conclusion.

Its all depending on how you use statistics, he said, comparing it further to deaths in automobile wrecks.

Its like the majority of people who die in a car crash were wearing a seatbelt, right? Weber said. Because almost everyone wears a seatbelt.

CBS 17sJoedy McCrearyhas been tracking COVID-19 figures since March 2020, compiling data from federal, state,and local sources to deliver a clear snapshot of what the coronavirus situation looks like now and what it could look like in the future.

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