*Major study confirms increased risk of death, serious illness among COVID-19 survivors
*Pregnant women with pandemic face high mortality rate, 11% of babies contracts virus from their mothers
*Babies of women infected with coronavirus more likely to be born preterm, researchers find
*WHO, UNICEF, Gavi highlight urgent need for renewed global commitment to improve vaccination access, uptake
A recent study published in the journal Nature showed that COVID-19 pandemic has derailed the fight against other dangerous diseases such as tuberculosis, measles, polio, malaria and Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS).
According to the Nature, after India went into lockdown in March 2020, the number of new tuberculosis (TB) cases detected there each day dropped by an alarming 70 per cent in one month.
Executive director of the Stop TB Partnership, an organisation in Geneva, Switzerland, that was set up to help combat TB, a disease that kills 1.4 million people a year, Lucica Ditiu, said: “It freaked us out.”
Ditiu was worried because the fall in India, the only country that collects real-time TB data, showed that cases were going undiagnosed and untreated as many nations diverted medical resources to tackling COVID-19. TB transmission would increase, she knew, because the disease is generally passed on through close contacts (at home or in prisons, for instance), which social distancing would be unlikely to prevent. And increased transmission would lead to more deaths.
Her fears were borne out. This March, the World Health Organization (WHO) announced that the number of people receiving TB treatment globally had dropped by more than one million, setting the fight against the disease back by a decade or more. An estimated 500,000 more people than usual might have died of TB last year, the WHO said.
Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, Peter Sands, at a Stop TB Partnership press briefing, said: “We face a potential calamity.”
The COVID-19 pandemic has disrupted prevention and treatment of a host of diseases. As countries went into lockdown last year, mass vaccination campaigns for measles, polio, meningitis and more ground to a halt, leaving millions of children at increased risk of deadly, preventable diseases. Some health facilities were closed; health-care workers were redeployed to fight the pandemic. Shipments of essential medicines and devices were delayed, and fewer people than usual sought treatment at clinics for fear of catching COVID-19.
More than a year into the pandemic, analysts are trying to gauge its impact on diseases that have largely slipped from public attention. For many diseases, it is too soon to see direct increases in illness and deaths, so researchers must rely on indirect measures — such as the number of children who have not been vaccinated, or falls in diagnoses — or on models, which are imperfect tools at best. Together, the data suggests that the knock-on effects of the pandemic could be larger than those caused by COVID-19 itself — and that they would linger long after the pandemic has ended.
The ramifications can be seen all over the globe, but the greatest effects will be felt in some of the poorest and most vulnerable countries, where health systems are already fragile. Three diseases typify COVID-19’s worrying impacts: TB, the biggest killer among all infectious diseases, especially among poor and marginalized people; measles, one of the most contagious viruses known, which is a major killer of young children in poor countries; and polio, the only virus currently targeted for eradication, which is clinging on in some parts of the world.
Last year, COVID-19 overtook TB as the infectious disease that caused the most deaths globally, but in low- and middle-income countries; TB was still the biggest killer. Caused by a bacterium (Mycobacterium tuberculosis), TB eats away at the lungs and kills its victims slowly, often years after the onset of an active infection.
About two billion people worldwide have latent TB infections in which their immune systems control the bacteria; five–10 per cent of those individuals will develop active TB in their lifetime. The 100-year-old bacillus Calmette–Guérin (BCG) vaccine can halt progression to severe forms of TB in children, but it does not prevent infection.
To tackle TB, physicians need to diagnose it and then treat it with a gruelling six-month regimen of medicines that can stretch to two years for drug-resistant strains. So Ditiu started to worry last March when she heard from other pulmonary specialists in her native Romania and elsewhere that they were being pulled away from TB to care for people with COVID-19. Some TB hospitals, well practised in dealing with a contagious respiratory disease, were being repurposed. During lockdowns, people with TB were having a hard time getting to clinics for diagnosis or to pick up their drugs. Then the India figures showed diagnoses plummeting.
The Stop TB Partnership soon teamed up with Imperial College London and others to model the impact of COVID-19 on the TB burden. In their worst-case scenario, released last May, a three-month lockdown with a 10-month recovery to normal TB services would lead to 6.3 million additional cases and 1.4 million excess TB deaths worldwide between 2020 and 2025.
A medical epidemiologist at Imperial who co-authored the study, Nimalan Arinaminpathy, said: “Last year’s worst-case scenario now seems too optimistic.” Because TB moves so slowly, it is too soon to know whether more people died of TB than expected last year. But indirect signs of trouble are abundant. This March, the WHO said that, around the world, 21 per cent fewer people received care for TB in 2020 than in 2019, a fall of 1.4 million. This formed the basis for its estimate that an extra 500,000 people have died of TB. Although India rebounded from its diagnosis nadir with an aggressive TB programme to regain lost ground, the number of newly detected cases there is still about 12 per cent shy of where it was pre-COVID.
Also, according to the Nature, before the coronavirus pandemic hit, global measles cases had soared to nearly 870,000 in 2019, with almost 210,000 deaths, mostly in young children. This was the highest level in decades, largely because underfunded health systems had struggled to keep up with routine childhood immunisations or conduct the large vaccination campaigns they rely on to ward off outbreaks when childhood immunisation rates are low. The measles virus is extremely contagious, and can cause diarrhoea, loss of sight or hearing, pneumonia and encephalitis (swelling of the brain). In combination with malnutrition, it kills an estimated three–six per cent of those it infects in poor countries.
So it was a blow in March 2020 when the WHO told countries to temporarily suspend all mass vaccination campaigns. By April, many countries had abruptly cancelled or postponed their campaigns. In May, the WHO issued guidance for safely resuming, but 24 countries still have not done so. James Goodson, a senior measles scientist at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, fears that those scheduled for 2021 will slip as well.
According to the WHO, for now, global measles cases remain curiously low. In 2020, they were down to about 89,000. Hampered surveillance might explain part of the drop, and because so many children caught measles in 2019, natural immunity levels are high. But the biggest factor, measles scientists say, is that COVID-19 lockdowns, travel restrictions and physical distancing have reduced the population mixing that fuel the spread of the measles virus.
Measles experts fear that this is the calm before the storm. The delayed campaigns have left a huge and growing pool of young children susceptible to measles. When the virus finds them, as COVID-19 restrictions ease, it will tear through the unprotected population.
Epidemiologist Balcha Masresha at the WHO’s regional office for Africa in Brazzaville, Congo, said the 2014–15 Ebola outbreak in West Africa shows what can happen when attention is diverted from measles, says. The outbreak upended health services as workers were sidetracked by Ebola, or died, and as clinics and other facilities shut. The number of children vaccinated against measles monthly fell by roughly 25 per cent in 2014 and 2015 in Liberia and Guinea, two of the worst affected countries. Although mass campaigns resumed in 2015, Liberia, Guinea and Sierra Leone saw thousands of cases in large measles outbreaks that continued two or three years after the Ebola epidemic ended.
The international groups that fight measles worldwide, including the WHO, the CDC, the American Red Cross, the United Nations children’s charity UNICEF and the UN Foundation, are desperate to avoid a repeat. In part to spur countries into action, the WHO and the CDC have prepared risk assessments for countries plagued by recurrent measles epidemics, focusing on Africa.
Director of maternal and child health and nutrition at Ethiopia’s Ministry of Health, Meseret Zelalem, said Ethiopia, Africa’s second-most populous country, needed no prodding. Just 60 per cent of children there have received their routine immunizations, and the last mass vaccination campaign for measles was conducted in 2017. Then the country delayed its April 2020 campaign. Projections suggested that thousands of children would die of measles in 2020 and 2021 if the country did not act. Although it wasn’t clear whether Ethiopia could conduct a campaign safely during a pandemic. “We found a way.” In July last year, outfitted with almost 395,000 face masks, more than 340,000 bottles of hand sanitiser and new protocols to ensure physical distancing, vaccinators fanned out across the country, reaching 14.5 million children — more than 95 per cent of the target population.
Ethiopia was the first large country to conduct a campaign in the current pandemic era, and international organisations hoped it would be a model for the rest of the world. Chad, a country that the CDC and WHO predicted was barrelling towards a huge outbreak, launched a measles campaign in January.
But other countries, worried about exacerbating the pandemic, still have their campaigns on hold. Experts fear that Guinea, Gabon, Angola and Kenya will face major outbreaks if they don’t conduct campaigns by the middle of this year.
Now, as COVID-19 vaccines arrive in Africa, health workers are likely to concentrate on delivering those rather than measles vaccines.
Meanwhile, the three-decade-long drive to eradicate polio was going backwards even before COVID-19 hit, and the pandemic has made a bad situation worse. In 2019 and 2020, cases of wild poliovirus rose in Pakistan and Afghanistan, the last two countries where it is endemic. And although Africa is free of wild poliovirus, polio strains derived from vaccines are raging there: these emerge in rare instances when the live, weakened virus used in Albert Sabin’s oral polio vaccine mutates into a strain that can spread in under-immunized communities and regains its ability to paralyse.
In March last year, the Global Polio Eradication Initiative (GPEI) in Geneva called for a pause in mass vaccination campaigns and repurposed some of its surveillance and laboratory infrastructure to the COVID-19 fight. More than 60 campaigns in 28 countries were postponed. Unpublished models from Imperial College London soon projected that polio cases could increase exponentially in some places if campaigns did not resume quickly. In late May, the GPEI called on governments to restart as soon as they had proper safeguards in place. But by the time they did so, the poliovirus, given free rein, had already taken off.
In Pakistan and Afghanistan, wild poliovirus expanded its reach, spreading from known reservoirs into previously polio-free areas — although total cases of paralysis in those two countries actually declined from 176 in 2019 to 140 in 2020. But there’s still a long way to go. Head of the GPEI, Aidan O’Leary, said: “In an eradication programme, the only number that counts is zero”. At the same time, cases of paralysis caused by vaccine-derived poliovirus increased from 22 in 2019 to 135 last year in Pakistan, and the strain jumped the border into Afghanistan, causing paralysis in 308 children in 2020. A vaccine-derived virus from Pakistan is now paralysing children in Tajikistan, which last saw a large polio outbreak in 2010.
WHO’s coordinator for polio eradication in Africa, Pascal Mkanda, said: “In Africa, vaccine-derived strains spread easily without any response. Cases climbed from 328 in 2019 to more than 500 in 2020, as the virus hopscotched the continent, affecting 6 new countries to bring the total to 18. Help might come from a new vaccine against vaccine-derived strains, which was approved in November, but it has yet to prove its mettle in the real world.”
Because vaccine-derived poliovirus is spreading so fast, stopping it is the first priority in Pakistan and Afghanistan while simultaneously hammering away at the wild virus. Massive campaigns are under way. In Africa, which has been plagued by slow, poor-quality campaigns that failed to reach enough children, the GPEI is now deploying rapid-response teams to act as soon as a vaccine-derived poliovirus is detected.
The GPEI must also deal with the problems that derailed the eradication effort before COVID-19. In Pakistan and Afghanistan, those include rumours about vaccine safety, vaccine refusals, the killing of polio workers, apathy and, in Afghanistan, and a Taliban bar on polio vaccinations that has left some 3.3 million children out of reach. In Africa, the situation has been complicated by unfounded rumours that polio vaccinators are using African children as guinea pigs to test COVID-19 vaccines.
For now, many countries remain laser-focused on COVID-19, with old problems such as measles, polio and TB taking the back seat. Other nations, such as Ethiopia and India, are already laying the groundwork for the long road back. Scientists and advocates talk optimistically about ‘building back better’, because deaths and illness from these old foes were too high before COVID-19. But with the course of the pandemic uncertain and the COVID-19 vaccine rollout only just beginning, no one is talking about when that might happen.
Meanwhile, researchers showed that COVID-19 survivors — including those not sick enough to be hospitalised — have an increased risk of death in the six months following diagnosis with the virus. They also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19 and revealing the massive burden this disease is likely to place on the world’s population in the coming years.
As the COVID-19 pandemic has progressed, it has become clear that many survivors — even those who had mild cases — continue to manage a variety of health problems long after the initial infection should have resolved. In what is believed to be the largest comprehensive study of long COVID-19 to date, researchers at Washington University School of Medicine in St. Louis showed that COVID-19 survivors — including those not sick enough to be hospitalized — have an increased risk of death in the six months following diagnosis with the virus.
The researchers also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19 and revealing the massive burden this disease is likely to place on the world’s population in the coming years.
The study, involving more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database, was published online April 22 in the journal Nature.
An assistant professor of medicine and senior author, Dr. Ziyad Al-Aly, said: “Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity.
“It is not an exaggeration to say that long COVID-19 — the long-term health consequences of COVID-19 — is America’s next big health crisis. Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades. Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care.”
In the new study, the researchers were able to calculate the potential scale of the problems first glimpsed from anecdotal accounts and smaller studies that hinted at the wide-ranging side effects of surviving COVID-19, from breathing problems and irregular heart rhythms to mental health issues and hair loss.
The investigators showed that, after surviving the initial infection (beyond the first 30 days of illness), COVID-19 survivors had an almost 60 per cent increased risk of death over the following six months compared with the general population. At the six-month mark, excess deaths among all COVID-19 survivors were estimated at eight people per 1,000 patients. Among patients who were ill enough to be hospitalized with COVID-19 and who survived beyond the first 30 days of illness, there were 29 excess deaths per 1,000 patients over the following six months.
The researchers analysed data from the national health-care databases of the U.S. Department of Veterans Affairs. The dataset included 73,435 VHA patients with confirmed COVID-19 but who were not hospitalized and, for comparison, almost 5 million VHA patients who did not have a COVID-19 diagnosis and were not hospitalized during this time frame. The veterans in the study were primarily men (almost 88 per cent), but the large sample size meant that the study still included 8,880 women with confirmed cases.
To help understand the long-term effects of more severe COVID-19, the researchers harnessed VHA data to conduct a separate analysis of 13,654 patients hospitalised with COVID-19 compared with 13,997 patients hospitalized with seasonal flu. All patients survived at least 30 days after hospital admission, and the analysis included six months of follow-up data.
The researchers confirmed that, despite being initially a respiratory virus, long COVID-19 could affect nearly every organ system in the body. Evaluating 379 diagnoses of diseases possibly related to COVID-19, 380 classes of medications prescribed and 62 laboratory tests administered, the researchers identified newly diagnosed major health issues that persisted in COVID-19 patients over at least six months and that affected nearly every organ and regulatory system in the body, including:
*Respiratory system: persistent cough, shortness of breath and low oxygen levels in the blood.
*Nervous system: stroke, headaches, memory problems and problems with senses of taste and smell.
*Mental health: anxiety, depression, sleep problems and substance abuse.
*Metabolism: new onset of diabetes, obesity and high cholesterol.
*Cardiovascular system: acute coronary disease, heart failure, heart palpitations and irregular heart rhythms.
*Gastrointestinal system: constipation, diarrhea and acid reflux.
*Kidney: acute kidney injury and chronic kidney disease that can, in severe cases, require dialysis.
*Coagulation regulation: blood clots in the legs and lungs.
*Skin: rash and hair loss.
*Musculoskeletal system: joint pain and muscle weakness.
*General health: malaise, fatigue and anemia.
While no survivor suffered from all of these problems, many developed a cluster of several issues that have a significant impact on health and quality of life.
Among hospitalised patients, those who had COVID-19 fared considerably worse than those who had influenza, according to the analysis. COVID-19 survivors had a 50 per cent increased risk of death compared with flu survivors, with about 29 excess deaths per 1,000 patients at six months. Survivors of COVID-19 also had a substantially higher risk of long-term medical problems.
In addition, the researchers found that the health risks from surviving COVID-19 increased with the severity of disease, with hospitalised patients who required intensive care being at highest risk of long COVID-19 complications and death.
Meanwhile, in a worldwide study of 2,100 pregnant women, those who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus.
UW Medicine and University of Oxford doctors led this first-of-its-kind study, published Monday in JAMA Pediatrics. The investigation involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 low-, middle- and high-income nations; 220 of the women received care in the United States, 40 at UW Medicine. The research was conducted between April and August of 2020.
The study is unique because each woman affected by COVID-19 was compared with two uninfected pregnant women who gave birth during the same span in the same hospital.
Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, preeclampsia and admission to the ICU and/or intubation. Of the mothers who tested positive for the disease, 11.5% of their babies also tested positive, the study found.
Although other studies have looked at COVID-19’s effects on pregnant women, this is among the first study to have a concurrent control group with which to compare outcomes, said Dr. Michael Gravett, one of the study’s lead authors.
One caveat, the researchers noted, was that women whose COVID-19 was asymptomatic or mild were not found to be at increased risk for Intensive Care Unit (ICU) care, preterm birth or preeclampsia. About 40 per cent of the women in this study were asymptomatic. Pregnant women who were obese or had hypertension or diabetes were at the greatest risk for severe disease, the findings showed.
Babies of the women infected with COVID-19 were more likely to be born preterm; but their infections were usually mild, the study found. Breastfeeding seemed not to be related to transmitting the disease. Delivery by Caesarean section, however, might be associated with an increased risk of having an infected newborn, the study found.
The World Health Organisation (WHO), UNICEF and Gavi, the Vaccine Alliance warned yesterday during World Immunisation Week, said while immunisation services have started to recover from disruptions caused by COVID-19, millions of children remain vulnerable to deadly diseases, highlighting the urgent need for a renewed global commitment to improve vaccination access and uptake.
WHO’s Director-General, Dr. Tedros Adhanom Ghebreyesus, said: “Vaccines will help us end the COVID-19 pandemic but only if we ensure fair access for all countries, and build strong systems to deliver them. And if we are to avoid multiple outbreaks of life-threatening diseases like measles, yellow fever and diphtheria, we must ensure routine vaccination services are protected in every country in the world.”
A WHO survey has found that, despite progress when compared to the situation in 2020, more than one third of respondent countries (37 per cent) still report experiencing disruptions to their routine immunization services.
Mass immunization campaigns are also disrupted. According to new data, 60 of these lifesaving campaigns are currently postponed in 50 countries, putting around 228 million people – mostly children – at risk for diseases such as measles, yellow fever and polio. Over half of the 50 affected countries are in Africa, highlighting protracted inequities in people’s access to critical immunization services.
Campaigns to immunize against measles, which is one of the most contagious diseases and can result in large outbreaks wherever people are unvaccinated, are the most impacted. Measles campaigns account for 23 of the postponed campaigns, affecting an estimated 140 million people. Many have now been delayed for over a year.
As a result of gaps in vaccination coverage, serious measles outbreaks have recently been reported in countries including the Democratic Republic of the Congo, Pakistan and Yemen, while likely to occur elsewhere as growing numbers of children miss out on lifesaving vaccines, the agencies warn. These outbreaks are happening in places already grappling with conflict situations as well as service disruptions due to ongoing response measures to COVID-19.
The supply of vaccines and other equipment is also essential for child vaccinations. Due to disruptions at the onset of the COVID -19 pandemic, UNICEF delivered 2.01 billion vaccine doses in 2020, compared to 2.29 billion in 2019.
To help tackle these challenges and support the recovery from the COVID-19 pandemic, WHO UNICEF, Gavi and other partners today launched the Immunization Agenda 2030 (IA2030), an ambitious new global strategy to maximize the lifesaving impact of vaccines through stronger immunization systems.
The Agenda focuses on vaccination throughout life, from infancy through to adolescence and older age. If fully implemented, it will avert an estimated 50 million deaths, according to WHO – 75 per cent of them in low- and lower-middle income countries.
Targets to be achieved by 2030 include: achieve 90 per cent coverage for essential vaccines given in childhood and adolescence; halve the number of children completely missing out on vaccines; and complete 500 national or subnational introductions of new or under-utilized vaccines – such as those for COVID-19, rotavirus, or human papillomavirus (HPV).
To achieve IA2030’s ambitious goals, WHO, UNICEF, Gavi and partners are calling for bold action:
World leaders and the global health and development community should make explicit commitments to IA2030 and invest in stronger immunization systems, with tailored approaches for fragile and conflict-affected countries. Immunization is a vital element of an effective health care system, central to pandemic preparedness and response, and key to preventing the burden of multiple epidemics as societies reopen
All countries should develop and implement ambitious national immunization plans that align with the IA2030 framework, and increase investments to make immunization services accessible to all
Donors and governments should increase investments in vaccine research and innovation, development, and delivery, focused on the needs of underserved populations
The pharmaceutical industry and scientists, working with governments and funders, should continue to accelerate vaccine Research and Development (R&D), ensure a continuous supply of affordable vaccines to meet global needs, and apply lessons from COVID-19 to other diseases.