Assessment of long-term adverse events regarding different COVID-19 vaccine regimens within an 18-month follow-up study.

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon.

PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.

SARS-CoV-2 Viral Shedding and Associated Factors among COVID-19 Inpatients and Outpatients.

Background: According to the contagious ability of the new virus, SARS-CoV-2, characterization of viral shedding duration in the period of infection is highly valuable in terms of providing quarantine guidelines and isolation policies. Therefore, we aimed at viral shedding determination in 58 COVID-19 confirmed Iranian subjects in different stages. Methods: 58 COVID-19 confirmed Iranian subjects including 21 outpatients and 37 inpatients were investigated. The analytical data and clinical properties were documented in the standard questionnaire. The RT-PCR tests were done two and three weeks after the symptoms initiation. Results: Viral eradication occurred in 44.8% two weeks after illness initiation whereas in 71% who achieved a negative PCR test in the third week. Moreover, prolonged viral shedding was observed in hospitalized cases in comparison to outpatients. Almost 30% of patients continued viral shedding three weeks after disease initiation. Conclusion: A longer duration of viral shedding in hospitalized cases rather than outpatients was observed in this study. The results similar to other investigations call into question if the current policies are enough to prevent the viral spread or not. This study should be done on a larger sample to provide an appropriate time in isolation policy.

Characterization of long COVID-19 manifestations and its associated factors: A prospective cohort study from Iran.

The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value < 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p < 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population.

SARS-CoV-2 re-infection rate in Iranian COVID-19 cases within one-year follow-up.

Since the COVID-19 pandemic initiation, the possibility of re-infection has been unclearly present. Although herd immunity has a potential reliance through natural infection, human corona viruses has the ability to subvert immunity and re-infection happens for seasonal corona viruses. Currently, the frequency of SARS-CoV-2 re-infection incidence is not exactly defined. In this study we aimed at determination of SARS-CoV-2 re-infection rate in Iranian population. In a total of 5696 COVID-19 suspicious individuals, RT-PCR was applied to diagnose the infection. The confirmed patients were followed for 12 months and serology tests were applied to measure the specific antibodies. Among 1492 confirmed COVID-19 cases, five individuals experienced the subsequent infection. The re-infection/reactivation incidence rate was totally 0.33% after one year of follow-up. The interval ranged from 63 to 156 days. All the cases had viral mutations in the second episode of the infection. All of them were symptomatic cases with moderate severity. The estimated rate of SARS-CoV-2 in Persian population is therefore rare and natural infection seems to induce good protection against re-infection which clarifies that mass vaccination can hugely affect the society.

SARS-CoV-2 presented moderately during two episodes of the infection with lack of antibody responses.

The world has gone through the critical phase of SARS-CoV-2 crisis caused by the new variants of the virus. The globally concerted effort to characterize viral genomic mutations across different clades has revealed several changes in the coding and also non-coding regions which might lead to a violent presentation or re-infection occurrence. Here, we studied a COVID-19 subject who represented the symptoms following the full recovery of the first infection. COVID-19 specific IgM and IgG were evaluated in both steps. The viral samples from oropharyngeal/nasopharyngeal were subjected to RT-PCR and full sequencing was done in both incidences. The sequencing data was fully investigated with the reference sequence of SARS-CoV-2 and the changes were detected. The obtained data is in favor of re-infection with 128 days of interval. SARS-CoV-2 presented more severely in the second episode of the disease and the specific antibodies against COVID-19 were not detectable. Both infections were caused by the same clade 20G, however, the mutation rates were higher in the second incidence including 10 nucleotide substitutions which had rarely been reported before. In the present study, the nucleotide mutations in various regions of the viral genome have been presented. The re-infection could have significant effect on clinical implications as well as vaccination.

Clinical characteristics of SARS-CoV-2 by re-infection vs. reactivation: a case series from Iran.

COVID-19 immunity in infected individuals may not be persistent. The specific response wanes in patients who have recovered from this infection. Nevertheless, it has not been fully understood whether true re-infection occurs or the viral reactivation. In this study, we investigated three COVID-19 patients who represented the symptoms after recovery. Chest CT scan was applied to assess the patients along with the viral samples from oropharyngeal/nasopharyngeal which were subjected to RT-PCR. The viral genome sequencing was applied where possible to distinguish possible re-infection or latent reactivation. Moreover, COVID-19-specific antibodies available data were evaluated in each incidence. The second episode of SARS-CoV-2 infection was different among the investigated subjects who experienced an interval between positive PCR tests ranged between 63 and 156 days. The disease presentation was less or more severe in the second infection. All cases were found IgG positive in the re-infection phase. The sequencing of SARS-CoV-2 sample obtained from two cases revealed a D614G mutation of S gene from the second isolated sample strengthens the case for the re-infection. The possibility of re-infection and reactivation could have significant effect on clinical implications and also vaccination. Our data supports clear warning of SARS-CoV-2 continuous circulation potency among the populations in spite of herd immunity either with natural infection or vaccination. This issue is critical in term of the patients, clinical investigate, and viral transmission.

Prolonged viral shedding and antibody persistence in patients with COVID-19.

SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.

Bioinformatics Analysis of SARS-CoV-2 to Approach an Effective Vaccine Candidate Against COVID-19.

The emerging Coronavirus Disease 2019 (COVID-19) pandemic has posed a serious threat to the public health worldwide, demanding urgent vaccine provide. According to the virus feature as an RNA virus, a high rate of mutations imposes some vaccine design difficulties. Bioinformatics tools have been widely used to make advantage of conserved regions as well as immunogenicity. In this study, we aimed at immunoinformatic evaluation of SARS-CoV-2 proteins conservancy and immunogenicity to design a preventive vaccine candidate. Spike, Membrane and Nucleocapsid amino acid sequences were obtained, and four possible fusion proteins were assessed and compared in terms of structural features and immunogenicity, and population coverage. MHC-I and MHC-II T-cell epitopes, the linear and conformational B-cell epitopes were evaluated. Among the predicted models, the truncated form of Spike in fusion with M and N protein applying AAY linker has high rate of MHC-I and MCH-II epitopes with high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. The in silico study provided truncated Spike-M-N SARS-CoV-2 as a potential preventive vaccine candidate for further in vivo evaluation.

SARS-CoV­2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the ongoing pandemic, has spread into more than 200 countries to date. The disease which is caused by the virus is termed COVID-19. In most cases, it presents at first like common flu with cough and other respiratory symptoms. Nevertheless, other symptoms have been reported, such as a feeling of extreme fatigue, gastrointestinal symptoms, or acute onset of olfactory and gustatory dysfunction. Here we report a series of 10 cases (1 male, 9 females) observed between February and April 2020, with an undulating appearance and disappearance of symptoms. Weeks passed before the diagnosis was established. Symptoms resolved rapidly after treatment with hydroxychloroquine. It seems that the course of COVID-19 can be mild or moderate but with a long persistence of symptoms, and may therefore remain obscure. This may cause a public health issue because of the long infectivity of these patients.