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Case Report

Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man

1
Human Genetics Lab, ALTAMEDICA, Viale Liegi 45, 00198 Rome, Italy
2
Department of Biochemistry, ALTAMEDICA, Viale Liegi 45, 00198 Rome, Italy
3
Department of Prenatal Diagnosis, Fetal-Maternal Medical Centre, ALTAMEDICA, Viale Liegi 45, 00198 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Submission received: 15 April 2021 / Revised: 7 May 2021 / Accepted: 15 May 2021 / Published: 17 May 2021
(This article belongs to the Collection SARS-CoV Infections)

Abstract

:
The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to spread throughout the world, causing more than 120 million infections. Several variants of concern (VOCs) have emerged and spread with implications for vaccine efficacy, therapeutic antibody treatments, and possible reinfections. On 17 March 2021, several VOCs were detected, including lineage B.1.1.7, first identified in the UK, B.1.351 in South Africa, Lineage P.1 (B.1.1.28.1) in Brazil, and novel Sub-Lineage A (A.23.1), reported in Uganda, and B.1.525, reported in Nigeria. Here, we describe an 83-year-old man infected with the SARS-CoV-2 P.1 variant after two doses of the BNT162b2 mRNA COVID-19 vaccine.

1. Introduction

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to spread throughout the world, causing more than 120 million infections. Several variants of concern (VOCs) have emerged and spread with implications for vaccine efficacy, therapeutic antibody treatments, and possible reinfections. Recently, a new SARS-CoV-2 lineage, P.1, was discovered in Manaus City, Amazonas, Brazil, in early January, 2020 [1,2]. The SARS-CoV-2 P.1 variant has a unique genetic profile of 17 amino acid changes, including three mutations (E484K, K417T, and N501Y) in the receptor-binding domain (RBD) region that are also present in the B.1.325 variant, a recent lineage that first emerged in South Africa [3]. It has been shown that B.1.351 is more resistant to neutralization by some monoclonal antibodies (mAbs), convalescent plasma, and vaccine sera, largely due to an E484K mutation that also exists in the P.1 lineage [1,4]. Of concern, in January 2021, the SARS-CoV-2 Lineage P.1 was able to cause a major second wave in Brazil [4]. In Italy, on 18 February, the prevalence of the Brazilian P.1 Lineage was 4.3%, ranging between 0% and 36.2% in different regions (ISS, second survey on the prevalence of variants of the Sars-CoV-2 virus (salute.gov.it, accessed on 19 March 2021)). This report describes an infective episode with SARS-CoV-2 Lineage P.1 occurring in an individual in Italy after the second dose of the Pfizer BNT162b2 mRNA COVID-19 vaccine [5].

2. Case Presentation

Here, we describe the case of an 83-year-old male who, on 16 January 2021 received the first dose of the Pfizer BNT162b2 mRNA COVID-19 vaccine, receiving the second dose on 16 February and completing the vaccination program. He received the vaccine in Santiago de Chile, South America, and he traveled back to Italy on 21 February. On 11 March, 2021 he was in close contact with a work colleague who had COVID-19—both the 83-year-old male and his work colleague are employed and live in Rome, Italy. On 17 March, we processed the 83-year-old male’s nasopharyngeal swab at the Altamedica Laboratory for SARS-CoV-2 detection by real-time RT-PCR, obtaining a positive result. His PCR test was found to be positive with cycle threshold (CT) values of the ORF1ab region, E and N genes 12, 13, and 12. To characterize the SARS-CoV-2 virus lineage, we performed a screening step of genotyping RT-PCR to detect the main SARS-CoV-2 mutations of the VOCs. This step was performed with custom TaqMan probes directed toward the following mutations: D1118H, T716I, S982A, del69-70, P681H, D614G, A570D, N501Y, del144, K417T, E484K, D215G, A701V, D138Y, T1027I. Once we detected the specific mutations of the P.1 variant (N501Y, K,417T, E484K, D138Y, D614G, and T1027I), we proceeded to perform next-generation sequencing (NGS) to confirm the lineage and investigate further mutations. In Figure 1 and Table 1, we report the unique amino acid changes revealed in the patient by NGS. In addition to the reported mutation in the GSAID database for the P.1. variant (S1188L, K1795Q, S3675-F3677del for orf1ab gene, L18F, T20N, P26S, D138Y, R190S, K417T, E484K N501Y, H655Y, T1027I, D614G for S gene, G174C for orf3a, E92K for orf8, and P80R for N gene), further missense mutations and variants with neutral effects have also been detected (Table 1). Among the missense mutations, we detected A1809V, V4225L, P4715L, D5130Y, and E5665D in the orf1ab gene, S640F and V1176F in the S gene, and RG203KR in the N gene. The result of Pangolin tool submission was, as expected from previous RT-PCR results, the Brazilian P.1 Lineage, a new and recently identified SARS-CoV-2 variant [3].
On 19 March, laboratory analysis showed a positive serologic test for the antibody anti-spike protein IgG, and total antibody anti-S1 SARS-CoV-2 virus, while the patient had a negative test for IgM and IgA antibodies (Table 2). Three days after a positive COVID-19 diagnosis, the patient had mild symptoms, such as headache and a cold. The symptoms were managed at home and resolved in two days. On 22 March, the patient repeated the nasopharyngeal swab, obtaining a further positive SARS-CoV-2 result with a significantly reduced viral load (ORF1ab CT 30, E gene CT 32, and N gene CT 31). Four days later, on 26 March, the PCR test was completely negative for all three genes (Figure 2).

3. Discussion

The spread of new SARS-CoV-2 variants represents a serious threat worldwide and, recently, it has been shown that an artificially created virus (pseudovirus) carrying the same mutations as the Brazilian P.1 variant also escaped from anti-receptor-binding domain (RBD) monoclonal antibodies and sera or plasma from convalescent or Pfizer BNT162b2-vaccinated individuals [6]. Another study showed that the immune plasma of COVID-19 convalescent blood donors had six-fold less neutralizing capacity against the P.1 lineage with respect to the B lineage [7]. Here, we described a fully BNT162b2-vaccinated 83-year-old man infected with the Brazilian P.1 SARS-CoV-2 variant. People are considered fully vaccinated for COVID-19 two weeks after they have received the second dose in a two-dose series (Pfizer–BioNTech). He had no symptoms, such as fever, cough, or shortness of breath, only experiencing a slight headache and mild cold. On 26 March, the PCR test was completely negative for all three genes, 10 days after his first positive PCR test, showing a shorter positive period with respect to the mean of infected patients. NGS analysis, besides confirming all the genetic variations typical of the P.1 lineage, identified other missense and neutral mutations, as shown in Table 1. Among them, we found the P4715L mutation mapped in the ORF1ab region, which a recent study found to be associated with a higher mortality rate for COVID-19 when linked to the S protein D614G mutation [8], also identified in our patient (Table 1). Similarly, we found missense mutation V1176F, present in the spike protein region, which is also correlated with higher mortality ratios and increased fitness of SARS-CoV-2 infection [9]. A qualitative serology test revealed the presence of IgG, and a quantitative serology test revealed the presence of 319.0 BAU/mL of total anti-spike SARS-CoV2 virus antibody. The serology test was carried out five weeks after the second dose of the Pfizer–BioNTech vaccine after the positive SARS-CoV-2 virus PCR test but two days before mild symptom onset. According to the literature reports, antibodies are usually detectable approximately 4-6 days after PCR confirmation of infection, suggesting that the revealed antibody response was mostly vaccine induced, rather than a natural immunity response to the virus. It has been estimated that the Pfizer–BioNTech vaccine has 90% effectiveness after the second dose in individuals aged 80 years or older, and at least 97% effectiveness against symptomatic COVID-19 cases, hospitalizations, and deaths [10]. Poor neutralization activity against the P.1 variant has been reported, mainly related to the E484K mutation alone or in combination with other mutations in the receptor-binding domain, reducing the vaccine efficiency, so fully vaccinated people should be mindful of the potential risk of becoming infected and transmitting the virus to other people [11,12,13].
What it is important to underline here is that, in this case, despite being 83 years old, the patient had almost no symptoms and completely recovered from COVID-19 disease after a few days, unlike his younger colleagues. In his place of work, a small outbreak occurred, infecting 19 out of 21 colleagues. In particular, four of them, with an age ranging from 54 to 61 years old, showed severe COVID-19 symptoms, resulting in bilateral pneumonia and oxygen supplementation and, for one of them, in hospitalization and intensive care unit (ICU) admission. Interestingly, no coworkers were vaccinated, and they had never had a positive COVID-19 test before. Notably, the seventy-five-year-old wife of the infected patient was vaccinated and at the time of her husband’s infection, she had an anti-spike SARS-CoV2 virus antibody titer of 1305 BAU/mL, four-fold higher than her husband, and although she lives in direct contact with him, she never contracted SARS-CoV-2 infection. As previously described in studies about SARS-CoV-2-positive patients and those who have recovered, neutralizing antibodies can provide protection from infection and attenuate disease symptoms [14,15]. Since the investigated patient is a frequent traveler often underwent to SARS-CoV-2 swabs diagnostic test, and he did not refer cold like symptoms since pandemic outbreak, so we can exclude that he was previously infected by the virus. In conclusion, the 83-year-old man described in this study as being infected with the Brazilian P.1 SARS-CoV-2 variant had mild symptoms, which resolved in only two days (Figure 2), so we can speculate that, regardless of the reported reduced efficacy of the Pfizer–BioNTech vaccine against the P.1 Brazilian variant, the vaccine-induced immune response attenuates the disease symptoms, which are often moderate to severe for >80-year-old individuals.

4. Materials and Methods

4.1. Detection of the SARS-CoV-2 Virus by Real-Time Polymerase Chain Reaction (RT-PCR)

Specimens were obtained from the patient by nasopharyngeal swab and blood collection. Nucleic acid extraction was performed using the automated PANA 9600s extractor system. Detection of the SARS-CoV-2 RNA was performed by RT-PCR (KHB, diagnostic kit for SARS-CoV-2). The assay targets three genes of SARS-CoV-2 (ORF1ab, N, and E).

4.2. SARS-CoV-2 Variant Characterization by RT-PCR and Next-Generation Sequencing (NGS)

An aliquot of extracted RNA underwent a retrotranscription (RT) step. cDNA was synthesized from the extracted RNA using the SuperScript IV VILO Master Mix (Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer’s instructions. The first step of RT-PCR was performed for the detection of the main SARS-CoV-2 mutations of the three variants. This step was performed with custom TaqMan probes directed at the following mutations: D1118H, T716I, S982A, del69-70, P681H, D614G, A570D, N501Y, del144, K417N, E484K, D215G, A701V, D138Y, T1027I. The sequencing analysis of SARS-CoV-2 was performed using an Ampliseq SARS-CoV-2 panel (TermoFisher Scientific). The reads from the library were aligned with the Wuhan-Hu-1 NCBI Reference Genome (Accession Number: MN908947.3) in Torrent Suite v. 5.10.1. For mutation calling, the following plugins were used: Coverage Analysis (v. 5.10.0.3), Variant Caller (v.5.10.1.19), and COVID19AnnotateSnpEff (v.1.0.0), a plugin specifically developed for SARS-CoV-2 that can predict the effect of a base substitution [16]. The software Integrative Genomics Viewer_2.8.0 (IGV) was used to visualize the torrent variant caller (TVC) bam files of each sample in order to check the consistency of nucleotide calls. Raw sequence reads were aligned to the complete genome of the SARS-CoV-2 Wuhan-Hu-1 isolate (Genbank accession number: NC_045512.2) and classified using the Pangolin COVID-19 Lineage Assigner tool v. 2.0.7 (http://pangolin.cog-uk.io/, accessed on 19 March 2021) [17].

Author Contributions

M.F. and K.M. conceived the study and provided insights with regard to data analysis. M.F. and A.V. performed the laboratory analyses. A.M. and C.G. participated in conceiving the study and drafted and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was approved by the local ethical committee of Artemisia SPA.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Schematic representation of mutation of analyzed patients’ SARS-CoV-2 with an aminoacidic missense change revealed by NGS. Genome IGV analysis that shows the three characterizing P.1 mutations in the reads from sequenced samples.
Figure 1. Schematic representation of mutation of analyzed patients’ SARS-CoV-2 with an aminoacidic missense change revealed by NGS. Genome IGV analysis that shows the three characterizing P.1 mutations in the reads from sequenced samples.
Pathogens 10 00614 g001
Figure 2. Timeline of vaccine, symptom onset, and molecular diagnosis of patient.
Figure 2. Timeline of vaccine, symptom onset, and molecular diagnosis of patient.
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Table 1. Number of gene mutations in SARS-CoV-2 genome of patient.
Table 1. Number of gene mutations in SARS-CoV-2 genome of patient.
PositionGeneHGVS_CHGVS_PMutation Effect
733orf1abc.468T > CD156Dsynonymous mutation
2749orf1abc.2484C > TD828Dsynonymous mutation
3037orf1abc.2772C > TF924Fsynonymous mutation
3828orf1abc.3563C > TS1188Lmissense mutation
5648orf1abc.5383A > CK1795Qmissense mutation
5691orf1abc.5426C > TA1809Vmissense mutation
6319orf1abc.6054A > GP2018Psynonymous mutation
6613orf1abc.6348A > GV2116Vsynonymous mutation
11287orf1abc.11023_11031delS3675_F3677delconservative inframe deletion
12778orf1abc.12513C > TY4171Ysynonymous mutation
12938orf1abc.12673G > TV4225Lmissense mutation
13851orf1abc.13587T > CG4529Gsynonymous mutation
13860orf1abc.13596C > TD4532Dsynonymous mutation
14408orf1abc.14144C > TP4715Lmissense mutation
15652orf1abc.15388G > TD5130Ymissense mutation
17259orf1abc.16995G > TE5665Dmissense mutation
26149orf3ac.757T > CS253Pmissense mutation
21614Sc.52C > TL18Fmissense mutation
21621Sc.59C > AT20Nmissense mutation
21638Sc.76C > TP26Smissense mutation
21974Sc.412G > TD138Ymissense mutation
22006Sc.444C > TN148Nsynonymous mutation
22132Sc.570G > TR190Smissense mutation
22812Sc.1250A > CK417Tmissense mutation
23012Sc.1450G > AE484Kmissense mutation
23063Sc.1501A > TN501Ymissense mutation
23403Sc.1841A > GD614Gmissense mutation
23481Sc.1919C > TS640Fmissense mutation
23525Sc.1963C > TH655Ymissense mutation
24642Sc.3080C > TT1027Imissense mutation
25088Sc.3526G > TV1176Fmissense mutation
28167orf8c.274G > AE92Kmissense mutation
28512Nc.239C > GP80Rmissense mutation
28881Nc.608_610delGGGinsAACRG203KRmissense mutation
Table 2. Patient characteristics and laboratory test results.
Table 2. Patient characteristics and laboratory test results.
PatientCharacteristics
Age83
SexMale
SymptomsHeadache and cold
Laboratory results
Sars-CoV-2 IgGPositive
Sars-CoV-2 IgMNegative
Sars-CoV-2 IgANegative
Sars-CoV-2 Ab anti-spike (RBD)319.0 BAU/mL
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Fabiani, M.; Margiotti, K.; Viola, A.; Mesoraca, A.; Giorlandino, C. Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man. Pathogens 2021, 10, 614. https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050614

AMA Style

Fabiani M, Margiotti K, Viola A, Mesoraca A, Giorlandino C. Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man. Pathogens. 2021; 10(5):614. https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050614

Chicago/Turabian Style

Fabiani, Marco, Katia Margiotti, Antonella Viola, Alvaro Mesoraca, and Claudio Giorlandino. 2021. "Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man" Pathogens 10, no. 5: 614. https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050614

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