‘New Wave’ Of COVID-19: BA4 – BA5 Cases Surge Again
As we enter the holiday season, multiple countries are experiencing significant rise in new COVID-19 infections with Omicron BA.4 and BA.5 lineages sparking outbreaks around the world. The rapid surge in new COVID-19 cases has raised major concerns regarding whether the world is about to face a new global wave of the disease and has spurred calls for greater caution and measures. Many experts link the current increase in COVID-19 activity with the circulation of new subvariants, the relaxation of pandemic measures, and increased travel, events, and gatherings during the summer season. Read along to find out more about the emerging subvariants, their role within the resurgence of infections, along with the efficacy of vaccines and tests against these subvariants.
What are the BA.4 and BA.5 subvariants?
The BA.4 and BA.5 subvariants of Omicron were detected during horizon monitoring on April 4, 2022. So far, the data has revealed that the BA.4 subvariant shares all but eight mutations/deletions with the BA.2 lineage. The BA.5 subvariant, with sample dates ranging from February 25 to March 25, 2022, carries all but four of the identical mutations/deletions as its BA.4 sibling. Noteworthy mutations of the BA.4 and BA.5 include a spike 69/70 deletion which causes an S-gene target failure, enabling a shortcut for the identification of the lineage. Further, the BA.4 and BA.5 subvariants also have F486V and L452R mutations in the spike protein, which have been previously linked to increased infectivity, pathogenicity, and immune evasion.
Why are the BA.4 and BA.5 subvariants are becoming dominant?
Current data on the BA.4 and BA.5 illustrate that these subvariants are 10% to 15% more infectious in comparison to previous subvariants of the Omicron strain such as BA.2. However, experts suggest that the primary factor underlying the growth of BA.4 and BA.5 is the improved ability of these subvariants to escape neutralizing antibodies produced by past infection or vaccination. Indeed, research at the Africa Health Research Institute has demonstrated that antibodies elicited by previous infections with the original Omicron strain were several times less effective against the BA.4 and BA.5 subvariants. Still, the study has also found that antibodies produced by vaccinated individuals were significantly more effective against the BA.4 and BA.5 subvariants compared to those elicited solely by past infection. According to the European Centre for Disease Prevention and Control (ECDC), the BA.4 and BA.5 subvariants do not appear to cause more severe disease, however, the upsurge in new COVID-19 cases might result in an increase in hospitalizations and excess deaths.
How do BA.4 and BA.5 subvariants contribute to the current resurgence of COVID-19 cases?
According to data by World Health Organization (WHO), with the circulation of BA.4 and BA.5 subvariants, daily COVID-19 cases within the 53 countries in the WHO European region have jumped from around 150.000 at the end of May to just under 500,000 earlier this month. According to Our World in Data (OWID), while in some countries the upsurge in cases has recently started to plateau, many countries within Europe including Portugal, Germany, France, Greece, Austria, Italy, Switzerland and Spain has experienced significant increase in incidence rates. In Portugal, BA.5 cases have reached almost 30,000 a day in June and accounted for 84% of all COVID-19 cases by June 5. Italy has recently experienced approximately 60% weekly increase in new COVID-19 cases, while the UK has reported a 43% jump in new infections. In the week between June 12 to 18, the number of new COVID-19 cases in France jumped by nearly 50%. According to Santé Publique France, BA.5 has jumped from 18% to 24% of sequenced cases in the week of June 6. Although the BA.4 and BA.5 subvariants have caused outbreaks primarily across Europe, data from the US Centers for Disease Control and Prevention (CDC) demonstrates that as of June 15, these subvariants account for more than one in three Covid-19 infections in America. Thankfully, however, while the rates of hospitalization and death have somewhat increased over these new waves of infection, the overall figures remain relatively low. As of July 3, the 7-day-rolling average of daily COVID-19 deaths in Europe is approximately 458. Likewise, the same figure for Germany (80), UK (70), Italy (63), Spain (45), France (38), Portugal (22), and Greece (18) illustrates that majority of the people are still well protected against severe disease.
Are vaccines and diagnostic tests still effective against BA.4 and BA.5 subvariants?
Although the BA.4 and BA.5 subvariants have an enhanced ability to evade neutralizing antibodies produced by natural infection or vaccination, vaccination still provides the best possible protection against severe disease and death. Experts also point out to the waiting immunity from vaccination or past infections, and underline the importance of increasing the vaccine uptake, especially of the high-priority population groups. Moreover, the reception of booster shots among eligible populations remains critical for the reduction of transmission, hospitalization, and death rates as they provide enhanced and prolonged immunity. Several new vaccines which aim to combine different variants of SARS-CoV-2 to broaden our immunity are also currently under development.
Surveillance and sequencing are essential to further our understanding of the characteristics of emerging variants and to develop more efficient pandemic responses, vaccines, tests, and treatments. Regardless of the variant or subvariant, molecular assays such as the polymerase chain reaction (PCR) tests remain highly accurate in the detection of SARS-CoV-2. There have not yet been comprehensive studies evaluating the sensitivity, specificity, and the overall accuracy of rapid antigen tests in the detection of BA.4 and BA.5 subvariants. However, given that the majority of these mutations are located in the spike protein, the mutations undergone by the BA.4 and BA.5 subvariants may affect the sensitivity and functionality of rapid antigen tests targeting the SARS-CoV-2 spike protein. On the other hand, the accuracy of rapid antigen tests targeting the nucleocapsid protein, including the RapidFor™ SARS-CoV-2 Rapid Antigen Test Kit, are relatively less likely to be altered by the mutations undergone by the BA.4 and BA.5 subvariants.
Regardless of the variant of concern, rapid antigen tests (RATs) are widely used in the detection of SARS-CoV-2. The use of rapid antigen tests offers unique benefits for purposes of public health by enabling simpler, quicker, and more affordable production, distribution, and application of diagnostic devices. Moreover, the use of rapid antigen tests reduces turn-around time and facilitate immediate isolation and access to care. Especially in congregate settings such as schools, workplaces, nursing homes, dormitories, homeless shelters, prisons where the rapid surveillance of large groups of people may be critical, rapid antigen tests can inform prevention and control measures. Further, rapid antigen tests may be utilized within remote or resource-limited areas which may lack sufficient access to laboratory technology, specialized equipment, and trained personnel. Finally, rapid antigen tests enable the quick detection of SARS-CoV-2 at the point of care. Some rapid antigen tests are designed deliberately for self-administration, and there are various options regarding sample type including saliva, nasal, and nasopharyngeal samples.
