Pre-existing immunity to SARS-CoV-2.

The study of the immune response to SARS-CoV-2 has been of great importance in response to the Covid-19 pandemic, both for the development of vaccines and for a better understanding of the epidemiology of the disease, to clarify why some individuals seem not to be contaminated or to have oligo/ asymptomatic symptoms.

It is speculated that cross-immunity between other human coronaviruses (HCV) may provide temporary protection against SARS-CoV-2. In a recent study, scientists investigated the presence of reactive antibodies to this virus in the serum of patients with and without a history of Covid-19. The main binding site of these antibodies is the spike glycoprotein, with its S1 and S2 subunits.

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Analysis of serum from patients with and without a history of Covid-19

Serum from 156 convalescent Covid-19 patients was studied, of which 154 presented IgM, IgG, and IgA simultaneously against the virus. In the other two patients, only IgG was detected. However, antibodies were also detected in the serum of patients with no history of SARS-CoV-2 infection from samples collected in a period before the pandemic. Such antibodies were detected in 5 of 34 individuals with other HCV infections and 1 of 31 patients without any coronavirus infection in these patients. In a subset of serum samples from children aged 1-16 years collected between 2011 and 2018, 21 of 48 patients detected reactive antibodies against SARS-CoV-2.

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In patients without Covid-19, antibodies were detected at lower titers, and the main class detected was IgG. Furthermore, the antibodies were mainly against the S2 subunit.

Conclusions

The presence of antibodies reactive to SARS-CoV-2 in serum samples collected before the pandemic reinforces the hypothesis of cross-immunity between coronaviruses as one of the protective mechanisms present in individuals. Furthermore, this detection was particularly higher in children and adolescents, which justifies a lower prevalence and severity of infection in this age group.

The pandemic brought numerous challenges to all health professionals, including those caring for children. Although the low hospitalization rates of children with Covid-19 compared to adults, about 1 in 3 hospitalized children need intensive care resources, similar to older patients, indicating that children become seriously ill and need specific support. 

Several protocols have been studied with adult patients, but there are still no specific treatment protocols for children. Supportive measures are used in most cases, but as the prognosis can be very poor in some cases, other therapies are sought to improve the evolution of these patients. 

Studies using Remdesevir, a nucleotide analog antiviral that inhibits the RNA polymerase of several viruses, including SARS-CoV-2, have been carried out in the adult population. Some studies show that the use of this treatment in critically ill patients, for 5 or 10 days, may benefit reducing the time to recovery of patients with moderate to severe disease. However, it has not shown benefits in terms of length of hospital stay and mortality. 

Studies with children with Covid-19

A study published in the journal Pediatrics in May 2021 analyzes the use of remdesevir in 77 pediatric patients hospitalized with Covid-19 in the United States and Europe. Although it is not a study to assess the effectiveness of medication in this population, it is presented as a study that provides an initial contribution regarding the safety of medication for children and brings new data regarding the clinical characteristics of severe pediatric disease.

The patients included in the study were hospitalized with severe Covid-19, with confirmation of viral infection performed with PCR ( polymerase chain reaction). Patients were included from hospitals that accepted the protocols established by the research group, excluding patients with renal failure, signs of severe liver damage, or evidence of multiple organ failure.  

Patients weighing more than 40 kg received a loading dose of 200 mg intravenously on the first day, with subsequent doses of 100 mg on the following days. Patients weighing less than 40 kg received a loading dose of 5 mg/kg intravenously on the first day, with subsequent doses of 2.5 mg/kg on the following days. The protocol established the use of the medication for ten days without the concomitant use of other experimental therapies for Covid-19. 

Patients were followed for 28 days after starting medication or until hospital discharge, or death occurred. There were no specific outcomes assessed by the study, as this is a preliminary study. Nevertheless, data related to the patients’ clinical outcomes, such as medication safety, need for respiratory support, hospital discharge, and recovery were evaluated. 

 Pediatric patient outcomes

The mean age of included patients was 14 years (range two months to 17 years), with 60% of patients being male. A total of 39 patients (51%) required invasive ventilatory support, and one patient required ECMO ( extracorporeal membrane oxygenation). Most patients who did not require invasive respiratory support needed another type of ventilatory support (non-invasive positive pressure ventilation, high-flow nasal catheter, low-flow nasal catheter), with only eight patients in room air during the hospitalization. 

Most children (79%) had underlying diseases, including asthma, obesity, neurological disorders, hematological diseases, or prematurity. Regarding the use of Remdesevir, 62% of the children received the ten recommended doses of medication. 

 On the 28th day of evaluation, 83% of patients recovered from their condition. 79% of patients with invasive ventilation had been extubated, and 87% of patients with non-invasive ventilatory support were in room air. About 73% of patients had been discharged from the hospital on the 28th of the assessment. Furthermore, most patients had presented an improvement in the classification of the clinical picture, measured by the modified ordinal scale, of at least one category. Four patients died, two from each ventilatory group. 

In multivariate regression analysis, the researchers found that patients with invasive ventilation and younger patients (≤ 12 years) had a longer time to disease recovery (p-values ​​of 0.0035 and 0.016, respectively). 

Regarding the side effects of Remdesevir, 32% of patients had at least one side effect, with a higher proportion of these events in the most severe patients (in need of invasive ventilation). The most common side effects were increased transaminases and anemia. Renal alterations (haematuria, toxic nephropathy, renal failure) were described, but in no case were they attributed to the use of the medication or indicated its discontinuation. Five patients needed to suspend medication use due to some adverse event, such as increased transaminases, rash, or relapse of acute lymphoid leukemia. 

The study is important because it is the first to evaluate the use of remdesevir in a large group of children. However, we must not forget that due to the limitations of the study design, it is not possible to assess whether the medication contributed to the improvement of the children included in the study. In addition, the follow-up time was short to assess potential long-term side effects. Despite this, the use of remdesevir seems safe in this age group, and further studies are needed to assess the benefit of using this medication in treating severe Covid-19 in children.

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All authors declared that there is no potential conflict of interest regarding.

1. Blair SN, Kampert JB, Kohl III HW, Barlow CE, Macera CA, Paffenbarger RS, et …

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