Covid-19 Continued To Kill Even Months After Patients’ Supposed Recovery

“Many patients developed complications--stroke, heart attack or embolism--six months to one year after being sick with Covid-19,” noted Nikhil Modi, senior consultant, respiratory, Indraprastha Apollo Hospitals in New Delhi, the doctor who treated Saini. “Those who reached the emergency on time were more likely to have been saved, but we lost some myocardial infarction cases, mostly the elderly.”

Science now confirms that being infected with Covid-19 is a risk factor for death in the six- to 18-month period thereafter.

In India, a study by the Indian Council of Medical Research (ICMR) involved the telephonic follow-up of 14,419 patients admitted for serious Covid-19 across 31 hospitals. Overall, 6.5% of those patients died within a year of discharge.

Some of the victims of Covid-19 were aged 18-45. Among them too, a history of moderate to severe Covid-19 disease and comorbidities were associated with post-discharge mortality.

Being vaccinated against Covid-19 before contracting the infection provided “around 60% protection against post discharge death”, according to the study published in August 2023.

Global studies corroborate this finding. This study of nearly 160,000 people in the UK published in Cardiovascular Research in January 2023 showed that Covid-infected persons were up to 81 times more likely to die of cardiovascular disease than uninfected persons in the first three weeks of infection, and five times more likely to die up to 18 months later. This study published in Frontiers in Medicine in December 2021, based on data from 13,638 people in the USA, showed that people younger than 65 hospitalised with Covid had a 233% higher risk of dying in the 12 months after the disease than uninfected persons. And this study published in Nature in November 2022, of close to 500,000 people in the USA, showed that Covid-19 increases the risk of pulmonary, cardiovascular, haematological, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders and diabetes, regardless of vaccination status.

Demystifying the 6.5% Covid-19 toll in the study sample

Most of the patients who died after seemingly recovering from Covid-19 were severe cases in whom the virus took its toll on the body, causing conditions such as lung fibrosis or kidney involvement, and that organ directly or indirectly eventually caused the mortality, said Amit Saraf, director, Internal Medicine at Jupiter Hospital, Thane with reference to the ICMR study.

In patients with mild Covid-19 who died, the immunity was low either due to age (the elderly and children) or because the person had recently undergone treatment for cancer or major surgery or because the person had an uncontrolled comorbidity, continued Saraf. “Being immuno-compromised increased the susceptibility of the patient to a complication that could not be managed and mortality ensued.”

Thirdly, patients who delayed seeking treatment for whatever reason were more likely to eventually succumb to the post-Covid-19 conditions, added Saraf.

Post-viral syndromes are not new

The ability of viruses to linger in the body and cause conditions after the host has seemingly recovered from the infection is not new.

To cite some examples, “Influenza can cause fatigue, the adenovirus can affect the heart, the coxsackie B virus can affect the heart and cause dilated cardiomyopathy, the Epstein Barr virus (infectious mononucleosis) can remain in the body for a long time and get reactivated, causing a number of complications,” Sushila Kataria, senior director, internal medicine, at Medanta Hospital in Gurugram, told IndiaSpend.

“H1N1 (swine flu) cases who land up in the ICU for acute respiratory distress syndrome are likely to develop long-term complications,” added Modi. “Myocarditis, shock and arrhythmias can happen during the course of dengue.”

With Covid-19, the number of people who were infected was very high because no baseline immunity existed, and hence the number of people experiencing post-viral syndromes was high as well, and so, the post-acute sequelae of Covid-19 (PACS), commonly called post-Covid conditions (PCC) or long Covid, came into the public discourse, continued Kataria. “Also, the fact that the pandemic compounded feelings of insecurity, isolation, depression, loneliness, anxieties due to the inability to exercise or the loss of livelihood exacerbated the after-effects.”

Based on the 651 million official Covid-19 cases globally, more than 65 million people are estimated to have long Covid-19, reckoning by an August 2022 study--of 76,422 people based in the Netherlands--that found that one in 10 infected people developed the syndrome. The aforementioned ICMR study found that 17.1% patients developed PCC. While long Covid cuts across ages and the severity of the acute phase of the disease, this study of 78,252 patients in the USA shows that one in three reported cases are in the 36 to 50 age group, and three in four cases are in non-hospitalised patients with mild acute illness.

Post-Covid conditions differed in the short- and long-term

Post-Covid conditions may be divided into early post-Covid and late post-Covid complications, said Ajeet Jain, cardio thoracic and vascular surgeon at Rajiv Gandhi Super Specialty Hospital in Delhi.

“The early post-Covid symptoms tended to mirror the symptoms that the patient had during Covid-19,” continued Jain. “For instance, patients with respiratory symptoms suffered from breathlessness and chest congestion, patients with diarrhoea developed abdominal pain, and patients who lost their sense of taste and/or smell developed headaches. Some patients developed psychosomatic symptoms and psychological disorders, but these may have been exacerbated by the lockdown and other social restrictions that were unprecedented.”

If you had a tendency to develop a disease or condition, it was likely to be exacerbated after contracting the Covid-19 virus, added Kataria. For instance, people who were prone to experience anxiety felt their condition become more pronounced after the pandemic. So much so that the anxiety (or whatever condition) became like a separate disease.

“Many people experienced socio-psychological factors like the inability to concentrate or not feeling normal. Also, we saw fungal infections, the reappearance of fever due to an inflammatory syndrome, continued dependency on oxygen, and fibrosis,” she said.

The late post-Covid symptoms have mainly been thrombotic, according to Jain.

Thrombus happens when blood clots block blood vessels. “People have developed thrombus, large enough to cause pulmonary embolism, cerebrovascular incidents or myocardial infarction, sometimes severe enough to be fatal,” said Jain.

What stood out in this development was that after Covid-19, even younger people, say, in their forties, developed coronary artery disease, and many of those patients were seen to have clean vessels or had developed the disease in only a part of their vessels, explained Jain. “Usually, myocardial infarction develops with age, say after 60, in people with risk factors like hypertension, diabetes, smoking, a family history, dyslipidemia (the elevated level of cholesterol in the blood), stress and high cholesterol, and often involves all the three vessels of the heart, which looked diseased.”

In some severe cases, these later post-Covid symptoms developed very quickly, and that led to the increased fatalities seen during the Delta wave.

Modi shares the example of his father-in-law, who was rushed to the hospital for myocardial infarction during the first wave of the pandemic, where he tested positive for Covid-19.

“Essentially he developed myocardial infarction due to the virus,” said Modi. “We saw many cases of myocardial infarction, pulmonary embolism, heart attacks and brain strokes both during the peak of the pandemic as well as thereafter.”

While we know that most of the people who developed long Covid had comorbidities, we do not exactly know why this happens, concluded Jain.

New study throws light on long Covid

In the absence of conclusive research, several hypotheses have originated to explain why the post-acute Covid syndrome happens.

Possibly, some of the viral load on the body remains. Chronic inflammation has also been cited to be a reason as has the development of auto-antibodies or tissue damage occurring due to non-resolving antiviral responses. Hypercoagulability, the tendency of blood to clot, may be another contributing factor. Autonomic dysfunction has also been linked with long Covid.

Now, a new study at the University of Pennsylvania published in Cell in October 2023 has put forward a connecting factor between common post-acute Covid symptoms such as brain fog, headaches, dizziness and memory impairment, and all of the postulations surrounding PCC.

Researchers concluded that the post-acute Covid syndrome is associated with reduced serotonin levels in the body.

Serotonin is a chemical that transmits messages between nerve cells, and impacts mood, sleep, digestion, blood clotting and other bodily functions.

The fall in serotonin levels happens because of several reasons. First, the intestinal absorption of tryptophan, the chemical that serotonin is made of, diminishes. Secondly, the storage of serotonin in platelets falls due to thrombocytopenia, or low platelet blood count. Thirdly, enzymes that metabolise serotonin are over consumed and produced.

The resulting deficiency of serotonin in the periphery reduces the activity of the vagus nerve, the main nerve controlling digestion, heart rate and the immune system. This, in turn, causes memory loss and dysfunction in the hippocampus, the part of the brain that stores and helps process memories.

Tracking the occurrence of Covid-19 complications

During Covid-19 outbreaks, physicians relied on the D-dimer and interleukin-6 (IL-6) investigations to evaluate the thrombotic load and the risk of cardiovascular disease, stroke and diabetes respectively.

“Patients who succumbed to Covid-19 had high D-dimer levels,” affirmed Jain.

“D-dimer indicates a hypercoagulability state implying a state where the risk of clotting is high,” said Modi. “Clots in vessels in the lungs can lead to embolism, a clot in the vessels of the heart can cause a heart attack, clots in the vessels of the brain can cause strokes. We put such patients on blood thinners for some months to prevent attacks and other complications.”

“Elevated levels of cardiac markers, NT-Pro BNP, CPK-MB, and non-cardiac investigations c-reactive proteins, serum ferritin, procalcitonin, and chest CT scans were used to evaluate patients,” continued Jain.

“We used c-reactive protein, an inflammation marker, and charted its trends,” added Modi.

Protecting against Covid-associated mortality

The biggest takeaway from the ICMR study is that individuals should do everything possible to boost their immunity, said Saraf. “This includes keeping a check on health parameters especially those associated with conditions you know you suffer from, and seeing a doctor if there is cause for concern.”

Since patients in the age group 18-45 also succumbed to Covid-19, Saraf emphasised: “immunity boosting applies to everyone.”

“Regular checks can help younger patients identify if they have a condition they are not aware of,” he said. “We saw many young Covid-19 cases with diabetes that they were not aware of. Younger patients are also more likely to indulge in excessive alcohol and smoking, and make unhealthy dietary choices.”

With the JN.1 variant of Covid-19, Saraf said that cases are milder, with mostly dry cough and throat pain. “The presentation nowadays is subtler,” he said. “We are not seeing the typical fever, wet cough, breathlessness, diarrhoea, and the involvement of the heart and kidney. While each case is judged by doctors, we are mostly prescribing antiviral medication only to those with comorbidities.”

While the ICMR study did not identify any precautions that can be taken to prevent post-Covid complications, author Aparna Mukherjee, also scientist E, in-charge, Clinical Studies & Trial Unit, Development Research, ICMR, pointed out that “vaccination against SARS-CoV-2 does protect against mortality even in the post-Covid period”.

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