Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences
Abstract
:1. Introduction
Virus Transmission between Sick and Asymptomatic Individuals
2. Variants
2.1. D614G Variant
2.1.1. Transmissibility
2.1.2. Infectivity Rate
2.1.3. Disease Severity
2.1.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.1.5. Viral Load
2.1.6. Reproduction Number (R0/Rt)
2.1.7. Vaccine Effectiveness and Vaccine Breakthrough
2.2. Alpha Variant
2.2.1. Transmissibility
2.2.2. Infectivity Rate
2.2.3. Disease Severity
2.2.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.2.5. Viral Load
2.2.6. Reproduction Number (R0/Rt)
2.2.7. Vaccine Effectiveness and Vaccine Breakthrough
2.3. Beta Variant
2.3.1. Transmissibility
2.3.2. Infectivity Rate
2.3.3. Disease Severity
2.3.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.3.5. Viral Load
2.3.6. Reproduction Number (R0/Rt)
2.3.7. Vaccine Effectiveness and Vaccine Breakthrough
2.4. Gamma
2.4.1. Transmissibility
2.4.2. Infectivity Rate
2.4.3. Disease Severity
2.4.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.4.5. Viral Load
2.4.6. Reproduction Number (R0/Rt)
2.4.7. Vaccine Effectiveness and Vaccine Breakthrough
2.5. Delta
2.5.1. Transmissibility
2.5.2. Infectivity Rate
2.5.3. Disease Severity
2.5.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.5.5. Viral Load
2.5.6. Reproduction Number (R0/Rt)
2.5.7. Vaccine Effectiveness and Vaccine Breakthrough
2.6. Omicron
2.6.1. Transmissibility
2.6.2. Infectivity Rate
2.6.3. Disease Severity
2.6.4. Affinity to Angiotensin-Converting Enzyme 2 (ACE2) Receptors
2.6.5. Viral Load
2.6.6. Reproduction Number (R0/Rt)
2.6.7. Vaccine Effectiveness and Vaccine Breakthrough
3. Epidemiological Factors
3.1. Weather Conditions and Environmental Factors
3.1.1. Air Pollution
3.1.2. Temperature, Humidity, and Wind Speed
3.2. Indoor Settings
3.3. Population Density, Race and Life Condition
3.4. Age
3.4.1. Children
3.4.2. Adults and Older Age
3.5. Gender
4. COVID-19 Disease Clinical Treatment Methods
4.1. Oxygenation and Ventilation
4.2. Antiviral Therapies
4.3. Anti-SARS-CoV-2 Neutralizing Antibodies
4.4. Steroid Treatment
4.5. Immunomodulatory Agents
5. Transmission Rate of Other Coronaviruses
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
SARS-CoV-2 Variant | Alpha | Beta | Gamma | Delta | Omicron |
---|---|---|---|---|---|
Scientific Name | B.1.1.7 | B.1.351 | P.1 | B.1.617.2 | B.1.1.529 |
First reported (geographical location/date) | United Kingdom September 2020 | South Africa May 2020 | Brazil November 2020 | India October 2020 | Botswana, South Africa November 2021 |
Number of mutations/spike mutation of interest | 23 mutations N501Y, D614G, P681H | 21 mutations K417N, E484K, N501Y, D614G, A701V | 17 mutations K417T, E484K, N501Y, D614G, H655Y | ∼23 mutations L452R, T478K, D614G, P681R | ∼50 mutations G339D, S371L S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, D614G, T547K, H655Y, N679K, P681R |
Transmissibility | ∼50–70% [100,105,106] compared to the wild type ∼30–40% [100] Compared to other circulating lineages ∼43–90% [104,108] compared to proceeding variants. | ∼23–50% [157,158,159] compared to ancestral lineages | 1.4–2.2 [193,197] times compared to the wild type and 46% [197] compared to previous variants. | 1.4–2.0 [229,237] compared to other lineages. 60–70% [232,233] more transmissible than B.1.1.7. | 2.7–3.7 [306,307] times compared to the Delta variant. |
Infectivity | 0.1% in early October to 49.7% in late November 2020 [63]. 3.7-fold rise in December 2020 [109]. | Reinfection cases were reported [163]. | 5.3% in the biweekly period of 11–24 April 2021 to 11.1% in the period of 23 May–5 June 2021 [202]. 0% in the period from November 2020 to 73% in January 2021 [203]. | 60% more infectious than the wild type [242]. 0.6% during April 2021 to 11.1% in May–June 2021, then surging to 83.2% in July 2021 [202]. | 13% to 73% in the period of 13–17 December 2021 [98]. >50% infections in mid-November 2021 [315]. 5.41-10-fold higher risk of reinfection than Delta [249,319]. Omicron is estimated to infect three to six times as many people as Delta over the same time [320]. |
Disease severity | 1.5 to 1.7 [114,499] increased risk of hospitalization 62% higher risk of hospital admission compared to wild type [120]. 30% to 50% greater mortality rate [119,122] 1.64 mortality hazard ratio compared to preceding lineages [121]. | 2.16–3.6-fold higher risk of hospitalization and a 2.23–3.3-fold elevated risk of ICU admission [166,168]. 1.24-fold higher risk of progressing to severe disease than B.1.1.7 and 1.57-fold increased risk of mortality [170]. | 1.7–2.6-fold higher risk of hospitalization and a 2.06–2.2-fold higher risk of ICU admission [166,208,209]. | 2.26–2.83-fold higher risk of hospitalization compared to the B.1.1.7 variant [115,248,251]. 108–120% higher risk of hospitalization, a 235–287% higher risk of ICU admission, and a 133–137% higher risk of mortality [243,251]. | 50–70% less likely to be admitted to hospital than those infected with the Delta variant [323,360]. Two-thirds reduction in the risk of COVID-19 hospitalization when compared to Delta [321]. |
Viral load/Ct values | The median Ct values for the ORF gene target (22.30 vs. 18.16; p < 0.0001) and N-gene target (23.16 vs. 19.39; p < 0.0001) were considerably lower in SGTF samples compared to non-SGTF samples [129]. Virus loads in SGTF samples can be 104 times higher than those in non-SGTF samples [129]. Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as determined by cycle threshold value (mean 28.8, SD 4.7 vs. 32.0, 4.8) [123]. | Viral load at symptom onset was higher in B.1.351 variants than in historical variants, with a Ct value of −1.15 (−1.57, −0.697) lower than preceding strains [171]. | Viral load was ten times (Ct = 19.8 vs. 23.0; p < 0.0001) higher than in non-Gamma patients [197]. Decrease in the median Ct values (25 to 22) from nasopharyngeal swab samples examined by RT-qPCR (p < 0.0001) between June 2020 and February 2021 [211]. | Larger viral loads and a longer Ct ≤ 30 [246]. Much larger viral load than wild-type infections, with median Ct values for the N gene of the Delta variant of 23.0, which is significantly lower than the wild-type N gene’s values (median: 36.5) [9]. Viral levels up to 1260 times higher than those infected with the original strain [260]. | Viral RNA content in the lungs was 3 log10 lower than in animals infected with D614G [338]. Mean peak Ct value for Omicron was 23.3 vs. 20.5 for Delta, underlining that the lower the Ct value, the higher the peak viral load [339]. Lower infectious virus loads than Delta-infected patients (5.2-fold, 0.715 log10) [341]. |
Estimated reproduction numbers (R0/Rt) | Rt = 1.25 during lockdown (UK) [132]. Rt increased 1.35 between September and December 2020, when compared to pre-existing variants (UK) [110]. R0 = 1–2 in November 2020 (UK) [104]. Rt = 1.4 in February 2021, then decreased to reach 1 in March, then 0.8 in April 2021 (Italy) [133]. R0 = 0.8–1.5 between January and March 2021 (Czech Republic) [134]. Rt > 2 between January and April 2021 (India) [136]. Rt = 1.44 between December 2020 and 3 February 2021 (Canada) [137]. Rt = 0.97 between August 2020 and January 2021, then increased > 1 from January 2021 to March 2021 [45], reaching 1.6 in January 2021 (Qatar) [45]. Rt varied from 1.1 to 2.8 (systematic review of ∼15 studies) [106]. | Rt = 1.55 (95% CI: 1.43–1.69) (based on data from multiple countries. including England, Wales, Scotland, Denmark, USA, and South Africa) until 12 February 2021 [138]. | Rt = 2.6 based on data collected before January 2021 (Brazil) [197]. Rt = 38% higher than non-VOCs, 10% higher than Alpha, and 17% higher than Beta (based on global data) until June 2021 [159]. | R0 = 3.2–5.0 between May and June 2021 (China) [239,265]. R0 = 5.08–6.0 in July 2021 (China) [266]. R0 = 5.2 during May 2021 (UK) [267]. | Rt = 0.8–2.5 in November 2021 (South Africa) [315,342]. Rt > 3 between November and December 2021 (UK) [319]. Rt was 4.2 times higher than the Delta variant (95% CI: 2.1, 9.1) during November 2021 (South Africa) [306]. R0 was equal to 1.90 (95% CI: 1.50–2.43) during November and December 2021 (South Korea) [343]. Rt = 3.19 (95% CI: 2.82–3.61) times more than that of Delta during December 2021 (Denmark) [344]. Rt = 2.5 during December 2021 (US) [345]. Rt = 1.8–3.1 in December 2021 (Italy) [346]. Rt = 1.34–3.57 depending on the location and vaccination rate, according to data obtained in many areas as of January 2022 (India) [377]. |
Vaccine Effectiveness Pfizer (BNT162b2) AstraZeneca (ChAdOx1) Moderna (mRNA-1273) Novavax (NVX-CoV2373) Johnson & Johnson (Ad26.COV2.S) | Estimated reduction in neutralization by less than 2-fold for both Pfizer and Moderna vaccines [145,146,148], by 5- to <10-folds for AstraZeneca and between 2 and <5-fold for Johnson & Johnson [147]. Novavax was 85.6% effective in reducing symptomatic COVID-19 infection (UK) [139,141]. Moderna was 88% effective 14 days after the first dose and 100% ≥ 14 days after the second dose [140]. Pfizer was 83% effective in the overall population and 93% in SARS-CoV-2-experienced subjects (100-day cumulative incidence: 5.78%) (Italy) [150]. | Estimated reduction in neutralization by 5 to <10-fold for Pfizer, Moderna, and AstraZeneca vaccines and by more than 10-fold for Ad26.COV2.S [147]. Novavax revealed 89% efficacy (UK) and 60% efficacy (South Africa) [181,182]. Moderna and Pfizer exhibited 1.2-fold reduced nAb titers 3–4 weeks post-second dose (US) [183]. Moderna was 72% (US), 66% (Latin America), and 57% (South Africa) effective 28 days after immunization [181,182]. Moderna was 61% effective after the first dose and 96% after the second dose [140]. | Estimated reduction in neutralization by 2 to <5-fold for Pfizer, Moderna, AstraZeneca, and Johnson & Johnson vaccines [147]. The median pseudovirus neutralizing antibody titers generated by Ad26.COV2.S were 3.3-fold lower against the P.1 variant [185]. Neutralizing ability of plasma from people who had previously been infected was 8.6 times lower against the P.1 isolates [218]. AstraZeneca vaccination was 77.9% effective against infection, 87.6% effective against hospitalization, and 93.6% effective against death following the two-dose regimen (Brazil) [214]. | Estimated reduction in neutralization by 5 to <10-fold for Pfizer, by 2 to <5-folds for Moderna and AstraZeneca vaccines, and by less than 2-fold for Johnson & Johnson [149]. Delta was found to be more resistant to neutralization of convalescent serum (by a factor of 2) and vaccine serum (by a factor of 2.5–3.33) than the wild-type virus in his investigation [277]. In 95% of people, two doses produced a neutralizing response, with titers against Delta being 3-to-5 times lower than those against Alpha [276]. Both the Pfizer and AstraZeneca vaccines reduced the neutralizing titer for B.1.351 by eight to ninefold [178]. Pfizer and AstraZeneca vaccine have similar efficacies against the Delta variant, with 30.7% following a single dose (UK) [269]. Two AstraZeneca doses were less effective (67%) against Delta variant infection (UK) [269]. Pfizer was 45.3% effective ≥14 days after the first vaccine dose and 51.9% effective ≥14 days after the second dose (Qatar) [270]. Pfizer provided 95% protection against infection in people aged 16 and older following the two-dose regimen (data obtained from US, Argentina, Brazil, South Africa, Germany, and Turkey) [271]. Moderna was 73.7% and 73.1% effective ≥14 days after the first and second doses, respectively (Qatar) [270]. Moderna was found to be 94.1-96.8% effective in avoiding COVID-19 sickness, including severe disease (US) [273]. Gam-COVID-Vac (Sputnik V) was 91.6% effective (Moscow, Russia) [274]. | Estimated 20- to 40-fold reduction in neutralizing activity with two doses of Pfizer vaccine [362] and by more than 10-fold for both AstraZeneca and Moderna vaccines [361,362]. 22.9-fold higher neutralization resistance than the ancestral D614G 3–4 weeks after receiving a second dose of either mRNA-1273 or BNT162b2 (US) [183]. Three to eightfold reduction in neutralization titers for Omicron compared to Delta in a study conducted in South Africa [359]. Pfizer was 70% effective during the proxy Omicron period (South Africa) [356]. Pfizer and Moderna booster effectiveness was ∼50% (Qatar) [304]. Reduced vaccine effectiveness against infection to 33%, down from 80% against Delta (South Africa) [295]. Pfizer and Moderna third/booster vaccine doses were associated with a 57% reduction in the risk of symptomatic infection when compared to 25 weeks after the second dose [321]. Booster doses (3X) were found to provide a high level or protection, exceeding 80% under certain circumstances [317]. Omicron may be twice as likely to evade existing vaccinations compared to Delta [299]. |
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Hoteit, R.; Yassine, H.M. Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences. Vaccines 2022, 10, 919. https://doi.org/10.3390/vaccines10060919
Hoteit R, Yassine HM. Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences. Vaccines. 2022; 10(6):919. https://doi.org/10.3390/vaccines10060919
Chicago/Turabian StyleHoteit, Reem, and Hadi M. Yassine. 2022. "Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences" Vaccines 10, no. 6: 919. https://doi.org/10.3390/vaccines10060919