RESUMO
Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acquired two additional changes previously associated with antibody escape and it could be identified as VOI1163.7.V2. Overall, we have detected the spread of a new Spike variant that may be advantageous to the virus and whose continuous transmission poses risks by the acquisition of additional mutations that could affect pre-existing immunity.
RESUMO
IntroductionCase registries of pregnant women diagnosed with coronavirus disease (COVID-19) by polymerase chain reaction (PCR) have reported that the majority experienced mild infection, but up to 9% may require critical care.1 Most COVID-19 cases published were in the third trimester of pregnancy, which could reflect reporting bias, higher risk of infection or increased disease severity in late pregnancy.2 Seroprevalence studies may allow reliable estimates of the susceptibility to infection and clinical spectrum since they include asymptomatic and mild infections not tested for PCR. We evaluated the seroprevalence and clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women in the first and third trimester. MethodsThe study was approved by the Institutional Review Board at each institution and informed consent was obtained. We recruited 874 consecutive pregnancies attending for first trimester screening (10-16 weeks gestation, n=372) or delivery (n=502) from April 14 to May 5. All women were interviewed with a structured questionnaire for COVID-19 symptoms two months prior to sampling. SARS-CoV-2 IgG and IgM/IgA antibodies were tested (COVID-19 VIRCLIA(R) Monotest, Vircell Microbiologist, Spain; reported sensitivity 70% IgG and 89% IgM/IgA, and specificity 89% and 99% respectively). Indeterminate results were re-tested (VITROS(R) Immunodiagnostic Products Anti-SARS-CoV2 Total Tests, Ortho Clinical Diagnostics, USA; 100% sensitivity and specificity) and re-classified as positive or negative. Women with COVID-19 were diagnosed and managed according to standard protocols and guidelines3,4. Statistical differences were tested using the{chi} 2 test or Student t-test as appropriate (p<0.05). ResultsA total of 125 of 874 women (14.3%) were positive for either IgG or IgM/IgA SARS-CoV-2 antibodies, 54/372 (14.5%) in the first and 71/502 (14.1%) in the third trimester. A total of 75/125 (60%) reported no symptoms of COVID-19 in the past 2 months, whereas 44 (35.2%) reported one or more symptoms, of which 31 (24.8%) had at least 3 symptoms or anosmia and 8 (6.4%) dyspnea. Overall, 7 women (5.6%) were admitted for persistent fever (>38{degrees}) despite paracetamol and dyspnea, of which 3 had signs of pneumonia on chest radiography. All 3 had criteria for severity (bilateral chest condensation, respiratory rate>30 and leukopenia) and required oxygen support but not critical care or mechanical ventilation, and they were all discharged well. The rates of symptomatic infection, hospital admission or dyspnea were significantly higher in third trimester women (Table and Figure). O_TBL View this table: org.highwire.dtl.DTLVardef@1efd3f2org.highwire.dtl.DTLVardef@43e612org.highwire.dtl.DTLVardef@1b5e673org.highwire.dtl.DTLVardef@12cc985org.highwire.dtl.DTLVardef@1627bfd_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable.C_FLOATNO O_TABLECAPTIONBaseline characteristics and clinical features of pregnant women positive for SARS-CoV-2 infection (N=125) in the first versus third trimester. C_TABLECAPTION C_TBL O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/20134098v1_fig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@ba4ad6org.highwire.dtl.DTLVardef@8742a5org.highwire.dtl.DTLVardef@28788dorg.highwire.dtl.DTLVardef@1029911_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure.C_FLOATNO Clinical spectrum of SARS-CoV-2 infection in pregnant women in the first and third trimester. C_FIG DiscussionThe 14.3% seroprevalence of SARS-COV-2 in pregnant women in this study was substantially larger than the contemporary rates of PCR positive cases (0.78%) reported for women 20-40y in Barcelona.5 The data confirm that COVID-19 is asymptomatic in the majority of pregnant women6 and illustrate the value of seroprevalence studies to capture the high proportion of asymptomatic or mild infections. In this study, none of the 125 pregnant women with SARS-CoV-2 infection required critical care as compared to 9% reported in cases diagnosed with PCR.1 However, the proportion of infections with symptoms or dyspnea was remarkably higher in the third trimester, and these results are in line with COVID-19 registries, reporting that 81% of hospitalized women were in late pregnancy or peripartum.1 These results provide reassuring information that, even in settings with a high prevalence, SARS-CoV-2 infection in pregnancy mostly presents with asymptomatic or mild clinical forms. The susceptibility to infection seemed to be the same in the first and the third trimesters of gestation. The data further suggest that, as with other respiratory viruses, COVID-19 could be more severe and require increased surveillance in late pregnancy. These findings should be confirmed and extended with larger consecutive prevalence studies in pregnancy.
