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Pulmonary Involvement in COVID-19 and ‘Long Covid’: The Morbidity, Complications and Sequelae
Published on: 15th June, 2021
Introduction: the perennial pandemic: There are serious challenges posed by the SARS-CoV-2 virus and COVID-19 as the disease. With the persistence of the pandemic over one and half year, it is being feared that the COVID-19 may have become the new reality associated with human existence world over and the mankind may have to live with it for years or even decades. Further, the grievous nature of the disease is evolving further with genomic changes in the virus in form of mutations and evolution of variants, with enhanced infectivity and probably virulence.
Acute and chronic phases of COVID-19: Epidemiologically, it is becoming clear that apart from the advanced age and pre-existing conditions, such as diabetes, cardiovascular, pulmonary, and renal diseases, certain constituent factors render some patients more vulnerable to more severe forms of the disease. These factors influence the COVID-19 manifestations, its course, and later the convalescence period as well as the newly defined ‘Long COVID phase. The substantial continuing morbidity after resolution of the infection indicates persisting multisystem effects of ‘Long Covid’.
Lung damage associated with COVID-19: COVID-19 is primarily a respiratory disease presenting with a broad spectrum of respiratory tract involvement ranging from mild upper airway affliction to progressive life-threatening viral pneumonia and respiratory failure. It affects the respiratory system in various ways across the spectrum of disease severity, depending on age, immune status, and comorbidities. The symptoms may be mild, such as cough, shortness of breath and fevers, to severe and critical disease, including respiratory failure, shock, cytokine crisis, and multi-organ failure.
Implications for the post-COVID care: Depending on the severity of respiratory inflammation and damage, as well as associated comorbidities, duration of injury and genetics, the progressive fibrosis leads to constriction and compression of lung tissues and damage to pulmonary microvasculature. Consequently, the COVID-19 patients with moderate/severe symptoms are likely to have a significant degree of long-term reduction in lung function. Depending on the severity of the disease, extensive and long-lasting damage to the lungs can occur, which may persist after resolution of the infection.
Managing the long COVID’s challenges: Given global scale of the pandemic, the healthcare needs for patients with sequelae of COVID-19, especially in those with lung affliction are bound to increase in the near future. The challenge can be tackled by harnessing the existing healthcare infrastructure, development of scalable healthcare models and integration across various disciplines with a combination of pharmacological and non-pharmacological modalities. Following clinical and investigational assessment, the therapeutic strategy should depend on the disease manifestations, extent of damage in lungs and other organs, and associated complications.
SARS-CoV-2 Infection, COVID-19, and long covid: Saga of erratic immune response, waning immunity, and immune system failure
Published on: 9th August, 2021
OCLC Number/Unique Identifier: 9157821475
Introduction - evolution of SARS-CoV-2 variants: With the unrestrained pandemic for over last one-and-half year, SARS-CoV-2 seems to have adapted to its habitat, the human host, through mutations that facilitate its replication and transmission. The G variant incorporating D614G mutation, potently more transmissible than the ancestral virus arose during January 2020 and spread widely. Since then, various SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with higher infectivity or virulence or both, have evolved on the background of G variant, and spread widely.
SARS-CoV-2 infection and the immunodynamics: As the virus becomes more transmissible, its lethality may drop. Apart from the humoral immunity, T-cell recognition from a previous SARS-CoV-2 infection or vaccination may modify the disease transmission correlates and its clinical manifestations. On the other hand, the immunity generated may reduce probability of re-infection as well as limit evolution of adaptive mutations, and emergence of highly infectious and immune-escape variants. There are complex issues related to the SARS-CoV-2 evolutionary dynamics and host’s immunodynamics.
Trending etiopathoimmunological correlates: The evolution potential of SARS-CoV-2 is limited because of proofreading function of nsp14. The S protein mutations affect transmissibility, virulence, and vaccine efficacy. The D614G mutation in G variant with higher infectivity has turned the Chinese epidemic into a pandemic. Other SARS-CoV-2 variants, such as Alpha, Beta, Gamma, and Delta seem to have evolved as result of adaptation to selective pressures during periods of prolonged infections and subsequent transmission. Further, there is issue of convergent association of mutations.
Basics of immunity and immune system failure: The nature of the immune response after natural SARS-CoV-2 infection is variable and diverse. There are pre-existing neutralizing antibodies and sensitized T cells elicited during previous infection with seasonal CoVs influencing the disease susceptibility and course. The virus has evolved adaptive mechanisms to reduce its exposure to IFN-I and there are issues related to erratic and overactive immune response. The altered neutralizing epitopes in the S protein in SARS-CoV-2 variants modify the immune landscapes and clinical manifestations.
Conclusion: current scenarios and prospects: Presently, the SARS-CoV-2 infection is widespread with multiple evolving infectious variants. There is probability of its transition from epidemic to endemic phase in due course manifesting as a mild disease especially in the younger population. Conversely, the pandemic may continue with enhanced disease severity due to evolving variants, expanded infection pool, and changing immunity landscape. There is need to plan for the transition and continued circulation of the virus during the endemic phase or continuing pandemic for indefinite period.
Exploring pathophysiology of COVID-19 infection: Faux espoir and dormant therapeutic options
Published on: 5th May, 2020
OCLC Number/Unique Identifier: 8620512199
COVID-19 virus structural components: The 2019-nCoV, also called SARS-CoV-2, was first reported in Wuhan, China in December 2019. The disease was named Coronavirus Disease 2019 (COVID-19) and the virus responsible for it as the COVID-19 virus, respectively, by WHO. The 2019-nCoV has a round, elliptic or pleomorphic form with a diameter of 60–140 nm. It has single-stranded RNA genome containing 29891 nucleotides, a lipid shell, and spike, envelope, membrane and hemagglutinin-esterase (HE) proteins.
Steps in progression of COVID-19 illness: Once inside the airways, the S protein on the viral surface recognizes and mediates the attachment to host ACE-2 receptors and gains access to endoplasmic reticulum. The HE protein facilitates the S protein-mediated cell entry and virus spread through the mucosa, helping the virus to attack the ACE2-bearing cells lining the airways and infecting upper as well as lower respiratory tracts. With the dying cells sloughing down and filling the airways, the virus is carried deeper into the lungs. In addition, the virus is able to infect ACE2-bearing cells in other organs, including the blood vessels, gut and kidneys. With the viral infestation, the activated immune system leads to inflammation, pyrexia and pulmonary edema. The hyperactivated immune response, called cytokine storm in extreme cases, can damage various organs apart from lungs and increases susceptibility to infectious bacteria especially in those suffering from chronic diseases.
The current therapeutics for COVID-19: At present, there is no specific antiviral treatment available for the disease. The milder cases may need no treatment. In moderate to severe cases, the clinical management includes infection prevention and control measures, and symptomatic and supportive care, including supplementary oxygen therapy. In the critically ill patients, mechanical ventilation is required for respiratory failure and hemodynamic support is imperative for managing circulatory failure and septic shock.
Conclusion: Confusion, despair and hopes: There is no vaccine for preexposure prophylaxis or postexposure management. There are no specific approved drugs for the treatment for the disease. A number of drugs approved for other conditions as well as several investigational drugs are being canned and studied in several clinical trials for their likely role in COVID-19 prophylaxis or treatment. The future seems afflicted with dormant therapeutic options as well as faux Espoir or false hopes. As obvious, not all clinical trials will be successful, but having so many efforts in progress, some may succeed and provide a positive solution. Right now, though, confusion and despair prevail.
Identifying patterns in COVID-19: Morbidity, recovery and the aftermath
Published on: 25th May, 2020
OCLC Number/Unique Identifier: 8600329092
The infectivity and pathogenesis: SARS-CoV-2, the causative agent of Covid-19, involves Angiotensin-converting enzyme 2 (ACE2) receptors on type II alveolar type 2 (AT2) cells in lungs. Apart from, the upper and lower respiratory tracts, the disease affects the gastrointestinal system prominently, as evidenced by the significant GI symptoms, early in the course of the disease. In addition, the virus infects ACE2-bearing cells in other organs including the heart and blood vessels, brain, and kidneys.
Clinical features and morbidity: The clinical spectrum of COVID-19 varies from asymptomatic or pauci-symptomatic presentation to moderate to severe states characterized by respiratory failure necessitating mechanical ventilation and ICU support and those manifesting critical clinical condition with complications like sepsis, septic shock, and multiple organ dysfunction failure. The CT chest is an important tool for early identification of COVID-19 pneumonia as well as for prognostic purposes.
The recovery and residual damage: The recovery and other outcomes vary depending on age and other aspects including sex, comorbidities, and genetic factors. The outlook for older adults, who account for a disproportionate share of critical disease, is unfavorable, and most of those who survive are unlikely to return to their previous level of functioning. The disease affects their long-term health and quality of life as well as brings in propensity for truncated post-disease survival.
COVID-19 aftermath and follow up: The patients discharged from hospital following severe COVID-19, continue to suffer with lingering impact of the disease as well as that of the emergency treatments that saved their life. The post-infection reduced exercise tolerance and other subtle factors, like post viral fatigue syndrome, post-traumatic stress disorder, impaired concentration, delirium, and disturbed sleep-wake cycle often underly the functional impairment. In fact, there is need of step-down care and later a multidisciplinary support involving regular clinical assessment, respiratory review, physiotherapy, nutritional advice, and psychiatric support.
Conclusion: The life after COVID-19: After recovery from the disease, the virus SARS-CoV-2, may persist for uncertain period. In addition, the chance of reinfection cannot be ruled out. The vitamin D supplementation may be helpful. In general, the quality of life (QOL) in ICU survivors improves but remains lower than general population levels, but most of the patients adapt well to their level of self-sufficiency and QOL. Also, the debility due to co-morbidities may further compromise the activity of daily living and QOL issues. The Age and severity of illness appear to be the major predictors of post-discharge physical functioning.
COVID-19 pandemic, recurrent outbreaks and prospects for assimilation of hCoV-19 into the human genome
Published on: 12th October, 2020
OCLC Number/Unique Identifier: 8683060462
The outbreaks and resurgence: The disease which reportedly began in the Chinese city Wuhan in November-December 2019, soon spread to various parts of the world, and was named and declared a pandemic disease by WHO. While the European countries were recovering from the epidemic, the disease took hold in the USA, the South American countries, Arabian countries, and South Asian countries, predominantly affecting Brazil, Peru, Iran, and India. Presently, many European countries are witnessing a resurgence and recurrent outbreaks of COVID-19.
Spread and evolving new insights: Whereas there is workplace-related infection rise as people are returning to their offices, in other places the outbreaks are related to the people crowding and meeting care-freely and trying to resort back to their earlier way of life. The reopening of the educational facilities across the continents may make matters worse.
Impact on health and healthcare: Most cases of COVID-19 infections go unnoticed and are followed by self-recovery. But what may appear good from the clinical perspective, appears to complicate epidemiological efforts to contain the outbreak. With the evolving information about the disease, there seem to be certain possible outcomes such as control and containment, or the persistence of the disease as global endemic accompanied with outbreaks and resurgent episodes.
Gnetic factors linked to disease severity: With the COVID-19 pandemic, not all infected patients develop a severe respiratory illness. Further, there is a large variation in disease severity, which may be due to the genetic factors underlying the variable response to the virus. It is becoming clear that apart from the advanced age and pre-existing conditions, certain genetic constituent factors render some patients more vulnerable to the more severe forms of the diseases.
Integration of virus into human genome: A significant part of the human genome is derived from viruses especially the RNA viruses. In fact, about 8 percent of the human genome is made up of endogenous retroviruses (ERVs), which are viral gene sequences that have become a permanent part of the human lineage after they infected our ancient ancestors. With this background, a novel concept emerging that if COVID-19 persists for several generations, its genetic material is projected to be integrated or assimilated into human genome. The involved mechanisms are conceptualized through the transposons or transposable elements of the SARS-CoV-2.
Stages in COVID-19 vaccine development: The Nemesis, the Hubris and the Elpis
Published on: 22nd December, 2020
OCLC Number/Unique Identifier: 8870065222
The nemesis: SARS-CoV-2 pandemic: Leaving in its wake millions of infections, accompanied by an immense magnitude of morbidity and multitude of mortality, and an unfathomable economic toll, the COVID-19 pandemic has led to a global calamity. An effective and safe COVID-19 vaccine is urgently needed to prevent the disease, thwart the complications and avert deaths resulting from unrestrained transmission of the infection.
The hubris: Vaccine development: While most of the platforms of vaccine candidates have focused on the spike (S) protein and its variants as the primary antigen of COVID-19 infection, various techniques involved include nucleic acid technologies (RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated and inactivated viruses. There are novel vaccine technologies being developed using next-generation strategies for precision and flexibility for antigen manipulation relating to SARS-CoV-2 infection mechanisms.
The elpis: Updates and prospects: There were nine different technology platforms under research and development to create an effective vaccine against COVID 19. Although there are no licensed vaccines against COVID-19 yet, there are various potential vaccine candidates under development and advanced clinical trials. Out of them, one having undergone phase III clinical trials, has become available in some countries for use among the high-risk groups following emergency use authorization. Other COVID-19 vaccines may soon follow the suit.
Conclusion: Hopes and concerns: The hope of benefiting from the vaccine to the extent that it may be the only way to tide over and control the COVID-19 pandemic, is accompanied by the likely fear of adverse effects and opposition in public for COVID-19 vaccination, including the vaccine hesitancy. Further, there is concern among scientific circles that vaccine may have opposite of the desired effect by causing antibody-dependent disease enhancement.
Exploring COVID-19: Relating the spike protein to infectivity, pathogenicity and Immunogenicity
Published on: 27th January, 2021
OCLC Number/Unique Identifier: 8906007931
Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pandemic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell.
Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials.
The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue.
Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.
Living with ‘Long COVID-19’: The long-term complications and sequelae
Published on: 16th February, 2021
OCLC Number/Unique Identifier: 9031344522
Introduction - the perennial pandemic: It is being increasingly realised that the COVID-19 may have become the new reality associated with human existence world over and the mankind may have to live with it for years or even decades. Further, the grievous nature of the disease is evolving further with the genomic changes in the virus in form of mutations and evolution of variants, with enhanced infectivity and probably virulence. There are serious challenges posed by the SARS-CoV-2 virus and COVID-19 as the disease.
COVID-19 as acute and chronic disease: On exposure to the SARS-CoV-2 virus, not all patients develop a disease. Further, for those who develop the disease, there is a large variation in disease severity. The known factors including the constituent factors and several still unknown factors influence the disease manifestations, its course, and later the convalescent phase as well. In fact, substantial continuing morbidity after resolution of the infection indicates persisting multisystem effects of COVID-19.
The ‘long COVID-19’ or ‘long haulers’: The patients who continue to suffer with persisting symptoms have been described as long haulers and the clinical condition has been called post-COVID-19 or ‘long COVID-19’. The diagnosis should be entertained if various symptoms and signs linger well beyond the period of convalescence in COVID-19. With the chronicity, there occur inflammatory changes and damage in various organs, and the extent of organ damage determines the long-term effects.
Management of ‘long COVID’ syndrome: The ‘long COVID’ syndrome has multi-system involvement, variable presentation, and unpredictable course. Following clinical and investigational assessment, the patients should be managed as per clinical manifestations, extent of organ damage and associated complications. The findings from various studies indicate that preventing further organ damage in ‘long COVID’ is crucial.
The long COVID’s prognostic challenges: As apparent, the ‘long COVID’ afflictions are more common than realized earlier. The symptoms can escalate in patients with co-morbid conditions. The persistent symptoms among COVID-19 survivors pose new challenges to the healthcare providers and may be suitably managed with a combination of pharmacological and non-pharmacological treatments, and holistic healthcare.
The Trans-zoonotic Virome interface: Measures to balance, control and treat epidemics
Published on: 9th April, 2020
OCLC Number/Unique Identifier: 8870064677
The global virome: The viruses have a global distribution, phylogenetic diversity and host specificity. They are obligate intracellular parasites with single- or double-stranded DNA or RNA genomes, and afflict bacteria, plants, animals and human population. The viral infection begins when surface proteins bind to receptor proteins on the host cell surface, followed by internalisation, replication and lysis. Further, trans-species interactions of viruses with bacteria, small eukaryotes and host are associated with various zoonotic viral diseases and disease progression.
Virome interface and transmission: The cross-species transmission from their natural reservoir, usually mammalian or avian, hosts to infect human-being is a rare probability, but occurs leading to the zoonotic human viral infection. The factors like increased human settlements and encroachments, expanded travel and trade networks, altered wildlife and livestock practices, modernised and mass-farming practices, compromised ecosystems and habitat destruction, and global climate change have impact on the interactions between virome and its hosts and other species and act as drivers of trans-species viral spill-over and human transmission.
Zoonotic viral diseases and epidemics: The zoonotic viruses have caused various deadly pandemics in human history. They can be further characterized as either newly emerging or re-emerging infectious diseases, caused by pathogens that historically have infected the same host species, but continue to appear in new locations or in drug-resistant forms, or reappear after apparent control or elimination. The prevalence of zoonoses underlines importance of the animal–human–ecosystem interface in disease transmission. The present COVID-19 infection has certain distinct features which suppress the host immune response and promote the disease potential.
Treatment for epidemics like covid-19: It appears that certain nutraceuticals may provide relief in clinical symptoms to patients infected with encapsulated RNA viruses such as influenza and coronavirus. These nutraceuticals appear to reduce the inflammation in the lungs and help to boost type 1 interferon response to these viral infections. The human intestinal microbiota acting in tandem with the host’s defence and immune system, is vital for homeostasis and preservation of health. The integrity and balanced activity of the gut microbes is responsible for the protection from disease states including viral infections. Certain probiotics may help in improving the sensitivity and effectivity of immune system against viral infections. Currently, antiviral therapy is available only for a limited number of zoonotic viral infections. Because viruses are intracellular parasites, antiviral drugs are not able to deactivate or destroy the virus but can reduce the viral load by inhibiting replication and facilitating the host’s innate immune mechanisms to neutralize the virus.
Conclusion: Lessons from recent viral epidemics - Considering that certain nutraceuticals have demonstrated antiviral effects in both clinical and animal studies, further studies are required to establish their therapeutic efficacy. The components of nutraceuticals such as luteolin, apigenin, quercetin and chlorogenic acid may be useful for developing a combo-therapy. The use of probiotics to enhance immunity and immune response against viral infections is a novel possibility. The available antiviral therapy is inefficient in deactivating or destroying the infecting viruses, may help in reducing the viral load by inhibiting replication. The novel efficient antiviral agents are being explored.
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