As at May 6, today, India’s coronavirus cases stand at 21,077,410 cases, with 230,168 deaths. India reported nearly 10 million cases in the month of April, and currently averages over 400,000 cases a day. From Maharashtra, Kerala, Karnataka, Uttar Pradesh, Tamil Nadu, Delhi to Andhra Pradesh — the story is the same: growing pain and confusion, cremations and a collapsing healthcare system. India is struggling to contain the second wave.

Hospitals have run out of beds. Oxygen supply is perilously low. Many people have died on the waiting line, on ambulances and car parks. With nearly 4000 deaths a day, the government’s principal scientific advisor, K. VijayRaghavan, has warned of a third wave.

“Phase 3 is inevitable, given the high levels of circulating virus… But it is not clear on what timescale this phase 3 will occur. We should prepare for more waves,” he said in a news briefing.

There is palpable fear in African countries as India’s caseload increases. Even though COVID-19 infections and fatalities remain comparatively low in the continent, African governments have struggled over the past year to expand healthcare capacity and meet vaccination targets. The continent has a fragile health ecosystem and cannot cope with the virulence of the double mutant currently devastating India.

According to John Nkengasong, director of the Africa Centers for Disease Control and Prevention, African countries “must be very, very prepared” in case a similar scenario plays in the continent.

“What is happening in India cannot be ignored by our continent,” he said, and urged African countries to avoid mass gatherings including political rallies.

“We do not have enough health care workers, we do not have enough oxygen,” he warned.

Many countries announced a ban on flights from India or issued travel advisories to all passengers in and out of India. Hong Kong suspended all flights connecting it with India after 50 passengers from two Vistara flights tested positive for COVID-19 on arrival. United Kingdom banned flights from India after 7 Indians tested positive for the new variant on arrival. Dubai banned all Indians and other international passengers who have visited India over the past month. Canada, Pakistan, New Zealand, Iran, Australia, Netherlands, Thailand, Italy, Portugal, United States, Germany, Singapore, Israel, and Nepal also instituted travel restrictions to India. The list is growing.

Kenya suspended flights to and from India following outrage on social media amid reports that a passenger plane had left India and was headed for Nairobi. On April 28 when the Health Cabinet Secretary, Mutahi Kagwe, announced the suspension of flights, Kenya was among a few countries still allowing passenger flights from India despite the risk of transmission.

Uganda suspended all passenger flights originating from India, on May 1, until further notice, and added that “all travelers who may have been in India or travelled through India in the last 14 days regardless of route taken shall not be allowed into Uganda.”

Tanzania, emerging from the COVID-19 denialism of the late President, John Pombe Magufuli, has announced a ban to all flights to and from India effective May 4, with exemptions being cargo planes and those undertaking operations related to humanitarian, diplomatic or medical assistance.

Rwanda’s national carrier, RwandaAir, has also suspended all flights to Mumbai, effective May 1, until further notice, joining a growing list of African Airlines, including Kenya Airways (KQ) and Uganda Airlines.

These measures were, unfortunately, belated. The double mutant has arrived in Africa. As of today, May 6, B.1.617 variant has been detected in two African countries: Kenya and Uganda. The variant has now been detected in more than 28 countries.

The Uganda Virus Research Institute (UVRI) reported Africa’s first case of the variant on April 30, forcing the country to ban flights from India with immediate effect. UVRI announced that B.1.167 was detected from travelers returning from India.

“We have picked up one case but are still looking for more because we are not yet sure whether the infected person had interacted with other people,” said Prof. Pontiano Kaleebu, the executive director of UVRI.

Dr. Patrick Amoth, the acting Director General for Health in the Ministry of Health, Kenya, confirmed on Wednesday, May 5, that the country had recorded five cases, Indian nationals who had travelled to the country before the flight ban.

“We picked this from a sample of Indian travellers who are doing some work in the western part of Kisumu. Health teams are doing contact tracing,” he said.

The government has not provided further details on these cases, but the situation in India should be a wake-up call to the Kenyan government’s lackadaisical approach to COVID-19 containment and management in the country.

The Africa Centers for Disease Control and Prevention has called for an emergency meeting of the continent’s health ministers to discuss preparedness is planned on May 8.

The Double Mutant

The variant, B.1.617, is responsible for the wave of infections and fatalities in India. The predominant lineage of B.1.617 was first identified in December 2020, though an earlier version has been traced to October 2020. Detailed analysis of the genome and proteins of B.1.617 confirm that it arose independently in India and differs from all the other variants circulating in the world today.

The B.1.617 variant contains two major mutations — E484Q and L452R mutations, which has given it the “double mutant” name, a misnomer because B.1.617 carries 13 mutations, with 7 on its spike protein. The double mutant name stuck because the two mutations, L452R and E484Q, appeared simultaneously and are widely considered to be responsible for the increased transmission and infectivity in India.

SARS-CoV-2, the virus causing COVID-19 disease, infects by attaching to cells using its spike protein. This protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor — the protein on the surface of human cells. After binding to ACE2, the virus undergoes a structural change that allows it to fuse with the cell. Once the virus gets inside the cell, it is able to reproduce and cause damage to body tissues.

In response to an infection, the body’s B cells secretes SARS-CoV-2 S protein antibodies with the aim of competing to bind to the S protein in the receptor binding domain (RBD) — a short immunogenic fragment from a virus that binds to the host’s receptors in order to gain entry into the cell. B cells are a type of white blood cells responsible for adaptive immunity, an acquired defense the body develops against foreign pathogens. It is characterized by specificity and memory, in that, when the body is first exposed to a virus, an antigen stimulates a primary response, and subsequent exposures stimulate a faster and stronger secondary response. Mutation in RBD makes it difficult for the body to utilize adaptive immunity to neutralize the virus and protect itself from disease.

SARS-CoV-2 S protein antibodies are secreted by B cells in aiming to compete with the host ACE2 for binding to the S protein RBD. Source: Sally Robertson

A study by Indian scientists published on bioRxiv — an open access preprint repository for biological sciences — on convergent evolution of SARS-CoV-2 spike mutations pointed out that B.1.617 possesses common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R in the spike protein, including the receptor binding domain (RBD) — the region critical for binding to ACE2 and antibody neutralization. These mutations increase the rate of ACE2 binding and S1-S2 cleavage rate, leading to increased transmission and decreased effectiveness of monoclonal antibodies (mAbs). Monoclonal antibodies are laboratory-made proteins that mimic the body’s immune system and help fight pathogens.

Source of visualization: William A. Haseltine

The L452R mutation substituted leucine with arginine amino acid at residue position 452. This change increased the affinity of the spike for the receptor and decreased the ability of the body to recognize the virus, including recognition by antibodies in convalescent serum and neutralizing monoclonal antibodies.

The E484Q mutation, in other variants such as B.1.351, P.1, and B.1.526, is a substitution of glutamic acid with lysine amino acid at residue position 484, meaning a substitution of a negatively charged amino acid with a positive one. The change reduces ability of convalescent antisera and monoclonal antibodies to neutralize the virus. It also increases affinity ACE2 receptor. The only difference between the E484Q mutation in B.1.617 and these other variants is that instead of substituting glutamic acid with lysine amino acid, it is replaced with a polar uncharged amino acid glutamine, which confers the variant greater immune evasion and increased ACE2 binding properties. It is for this reason that the E484Q mutation has been referred to as an “escape mutation” because it enables the virus to evade immune protection.

The P681 mutation is a substitution of proline for arginine amino acid at residue position 681, which is near the cleavage site of S1 and S2. This increases infectivity of virus particles by cleaving the S precursor protein to the S1/S2 configuration. This mutation is also unique to the Indian variant.

Can Vaccines Help?

There is hope that India’s new vaccine, Covaxin, can help neutralize the variant. Covaxin has been jointly developed by Bharat Biotech and the Indian Council of Medical Research. It is one of the many public-private collaborations, where public money is allocated to private enterprise to develop vaccines.

COVAXIN® is an inactivated vaccine developed using whole-virion inactivated vero cell derived platform technology. According to the manufacturer’s description, “inactivated vaccines do not replicate and are therefore unlikely to revert and cause pathological effects. They contain dead virus, incapable of infecting people but still able to instruct the immune system to mount a defensive reaction against an infection.”

A new study conducted by Indian Council of Medical Research (ICMR) in association with the National Institute of Virology has demonstrated potential effectiveness against the Indian double mutant, as well as the Brazil and UK variants.

Covaxin has been approved for emergency use, but there are heightened calls for voluntary licensing to boost production. Writing for the Hindustan Times, Prabhash Ranjan called on the government to urgently license the production of Covaxin to as many pharmaceutical companies as possible to augment the production and supply of the vaccine.

India, having proactively pushed for a temporary waiver of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement for Covid-19 vaccines, therapeutics, and related technologies, should also exercise the same political will to grant accessibility of the vaccine to African countries and ensure that intellectual property rights do not become a barrier to battling the double mutant.

The Biden Administration has added its weight on the suspension of vaccine patents question. President Biden supports the waiving of intellectual property rights for coronavirus vaccines. The support of the United States government could pave the way for the lifting of World Trade Organization’s intellectual property protections and allow pharmaceutical companies, globally, to manufacture approved vaccines. US Trade Representative, Katherene Tai, announced at the World Trade Organization, that the US supports the vaccine patent waiver proposal.

“The administration believes strongly in intellectual property protections, but in service of ending this pandemic, supports the waiver of those protections for Covid-19 vaccines,” she said.

It is a highly laudable stance from the Biden Administration, and a much-needed voice for the extraordinary proposal drafted by India and South Africa, to tackle the global pandemic. While the United States support is preliminary and does not guarantee a waiver, especially in the face of strong resistance from the European Union, it is a step in the right direction.

Africa relies heavily on vaccine supplies from India. The Serum Institute is the source of the AstraZeneca vaccines distributed by the global COVAX project to get doses to low- and middle-income countries. John Nkengasong, the director of the Africa CDC, observed that India’s export ban on vaccines “has severely impacted the predictability of the rollout of vaccination programs and will continue to do so for the coming weeks and perhaps months,” Nkengasong said. “We are living in a world that is extremely uncertain now,” he added.

There is a likelihood that the second wave in India will delay the progress of African vaccination programs, a reality which reminds African countries of the need to radically upscale investment in scientific research & development as a foundation for the emergence of a thriving pharmaceutical industry, capable of manufacturing drugs, vaccines and medical equipment to meet the growing needs a billion people.