L.P. Khoroshinina, Doctor of Medical Sciences, Professor, St. Petersburg State Paediatric Medical University, Professor V.A. Waldman Department of Faculty Therapy
Lawson Arman. H, Doctor of Medical Sciences, Professor
SUMMARY. Older individuals are particularly susceptible to SARS-CoV-2 infection and are at significant risk of unfavourable clinical outcome. In the elderly and older adults, lung damage caused by SARS-CoV-2 has distinct clinical, laboratory, and biochemical features. Geriatric patients with SARS-CoV-2 require an individualised approach, taking into account age-related changes in their body, the presence of comorbidities, and the high risk of adverse adverse reactions developing in response to drug administration. Any drug used in the treatment regimens of an elderly or old person infected with SARS-CoV-2 requires special attention due to the existing age-related features and polymorbidity in the geriatric patient. Currently, there is a lack of information on all the consequences that may be caused by COVID-19 infection, even more so in the elderly and old. Available scattered studies do not provide a complete clinical picture of the course and treatment of COVID-19-associated pneumonia in the elderly.
KEY WORDS: coronavirus infection, SARS-CoV-2, geriatric patient, lung lesions, pneumonia, COVID-19, elderly and old people.
PECULIARITIES OF THE COURSE OF CORONAVIRUS INFECTION AND SOME ASPECTS OF TREATMENT OF GERIATRIC PATIENTS WITH SARS-COV-2-INDUCED LUNG DAMAGE.
Lidiya P. Khoroshinina, Svetlana O. Lopatieva, Anastasia A. Lazareva
Saint-Petersburg State Pediatric Medical University. 194100, Saint-Petersburg,
Contact information: Lidiya P. Khoroshinina Professor, Doctor of Medical Sciences, Professor of the Department of Faculty Therapy named after Professor V.A.Waldman of the St. Petersburg State Pediatric Medical University.
SUMMARY. Older adults are particularly susceptible to SARS-CoV-2 infection and are at significant risk of adverse clinical outcome. SARS-CoV-2-induced lung injury has its own clinical, laboratory and biochemical characteristics in the elderly and elderly. Geriatric patients with SARS-CoV-2 require an individualised approach taking into account age-related changes in their body, presence of concomitant diseases, high risk of adverse reactions developing in response to drug administration. Any drug used in treatment regimens of an elderly or elderly person infected with SARS-CoV-2 requires special attention due to the age-related features and polymorbidity present in the geriatric patient. Currently, there is a lack of information about all the effects that can be caused by COVID-19 infection, especially in the elderly and old. The scattered studies available do not provide a complete clinical picture of the course and treatment of COVID-19-associated pneumonia in the elderly
KEY WORDS: coronavirus infection, SARS-CoV-2, geriatric patient, lung lesions, pneumonia, COVID-19, elderly and old people.
INTRODUCTION
Coronaviruses are known to be a heterogeneous family of large RNA viruses widely distributed among mammals and birds [53], but alpha- and beta-coronaviruses belonging to the respective genus of the said family can be invasive to humans [43]. The cellular tropism of the virus is determined by the susceptibility of host cells to infection, which is partly due to the presence of the angiotensin-converting enzyme receptor required for virus entry into the cell. In the case of SARS-CoV-2, the said receptor is expressed in the lung, small intestine, kidney, heart, thyroid, and adipose tissue [35]. At the end of the second decade of the 21st century, there was an outbreak of a new coronavirus, named SARS-CoV-2, which is capable of causing severe acute respiratory syndrome [31]. The term coined for the disease caused by SARS-CoV-2 has the name COVID-19[64]. The airborne route of infection and close social contact have been considered the main routes of transmission of COVID-19 [85], although a faecal-oral route of spread cannot be ruled out [86].
CLINICAL MANIFESTATIONS AND IMMUNE SYSTEM RESPONSE IN RESPONSE TO SARS-COV-2 INFECTION IN ELDERLY AND OLD PEOPLE.
Common symptoms of COVID-19 are fever, cough and asthenisation; other symptoms that have also been observed include: headache, diarrhoea and anosmia [70]. The clinical manifestations of COVID-19 range from mild symptoms (fever, dry cough, dyspnoea) to an acute and severe respiratory syndrome that can lead to the death of the patient [16]. The asymptomatic course of the disease is now also known [58]. In addition to lung damage, SARS-CoV-2 affects other organs [84] because of its tropism to many tissues [35]. Evidence suggests that for the elderly and seniors, SARS-CoV-2 infection is often a predictor of mortality [82]: among COVID-19 patients, the elderly and old die more often than younger patients [88; 49; 75; 59].
In patients infected with SARS-CoV-2, there is a dissociation between the severity of hypoxaemia and a relatively well preserved ventilatory mechanism [28]. Histological examination of postmortem lung biopsy specimens from 19 patients with COVID-19 revealed diffuse alveolar lesions [84], hyaline membrane formation, vascular thrombosis and large areas of intraalveolar haemorrhages, the presence of CD61+, and the presence of megakaryocytes located in alveolar capillaries [78; 27]. In patients infected with SARS-CoV-2, a pronounced immune response restrains the development of infection, but excessive cytokines and inflammatory mediators lead to a worse outcome for the patient. Leukocytosis, elevated ALT, lactate dehydrogenase, troponin I, creatine kinase, D-dimer, prothrombin time, serum ferritin, procalcitonin and IL-6 were associated with death in a study of 191 patients infected with SARS-CoV-2 [88]. Higher concentrations of cytokines IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A and TNFa have been reported in patients in the ICU compared to patients who were not admitted to the ICU [37]. The increase in excessive cytokines causes a cytokine ‘storm’ which, along with impaired anti-inflammatory mechanisms, can cause an imbalance in the coagulation system leading to lethal outcomes [17; 55; 20; 22; 57; 61; 62]
In aging, the body’s immune defence system changes due to the lack of CRELD gene activity, resulting in a sharp decrease in the number of T cells, which, deprived of the CRELD1 gene, lose the ability to reproduce and die – this phenomenon, called immunosenescence, is often observed in elderly and old people [9]. Immunosensation is a proven feature of aging processes. Both innate and adaptive functions of the immune system are markedly impaired with age, in addition, inflammatory mediators and pro-inflammatory cytokines are continuously produced in the elderly and old, unlike young people [6; 52; 56], and complex interactions between innate and adaptive immune effector cells are important for a competent response in response to the introduction of microorganisms into the macroorganism [2; 14]. Viral infections, especially those causing chronic or latent infections, have been suggested to affect T-cell function in the elderly: a negative correlation between CD4/CD8 T-cell ratio and the severity of such diseases in the elderly has been reported [2; 33]. The efficacy of vaccination given in the elderly against influenza-like illnesses is reduced compared to younger subjects, reflecting impairment of both effector memory T cells and effective B cells [63; 83; 7]. The impact of these immune system features on the course of COVID-19 in elderly and old patients remains poorly understood. In addition to the higher susceptibility of geriatric patients to SARS-CoV-2, differences in morbidity, mortality in men and women have been identified, with higher mortality rates in men [44; 46; 3; 18]. In patients with COVID-19 and acute respiratory distress syndrome, increased severity of illness was associated with patient gender and age [44; 3]. Men produce less robust immune responses and are more susceptible to infectious agents [50]. In fact, aging men have a more dramatic decrease in total T and B cell numbers and a greater increase in the number of senescent CD8 + memory T effector cells compared to women [15]. Most elderly men have an inverted CD4/CD8 T-cell ratio compared to women of the same age [34], in addition, the capacity of T cells for proliferation and cytokine secretion is more reduced in elderly men than in elderly women [74].
The clinical presentation in elderly and old patients with COVID-19, as in young adults [47], is characterised by common symptoms such as fever, cough, sputum and less common clinical features manifested by runny nose, headache, diarrhoea. In the group of elderly patients who died, complaints of marked dyspnoea and tachypnoea were more common during the illness, while fever and headache were more common in survivors [82]. Immobilisation, muscle pain, general weakness, fatigue, and dyspnoea were frequently seen specifically in geriatric patients hospitalised for COVID-19 [39; 80; 72; 67; 60]. The pneumonia severity index score was higher in the elderly patient group compared to the young and middle-aged group. Developing atypical pneumonia in elderly and old people may present with delirium, unexpressed elevation of body temperature and abdominal pain, which complicates the diagnostic search [30; 60]. Despite treatment, some elderly patients with COVID-19 terminal pneumonia progress to irreversible loss of lung function [45].
FEATURES OF LUNG LESION DIAGNOSIS IN ELDERLY AND OLD PATIENTS WITH COVID-19
In a single-centre retrospective study in elderly patients, there were no significant differences in white blood cell count, neutrophil ratio, procalcitonin, haemoglobin, platelet and serum creatinine levels, but the proportion of lymphocytes was significantly lower in the elderly compared with the young and middle-aged groups; but C-reactive protein was significantly higher in elderly patients [47]. Comparison of laboratory results between the groups of elderly patients with survivors and deceased individuals during a 4-week follow-up, showed that in the clinical blood count, in the subsequently deceased individuals, there was a significant increase in neutrophils but a decrease in lymphocytes, monocytes, and platelets. In this group, in the biochemical blood tests, there was a significant increase in prothrombin time, urea, creatinine, D-dimer and markers of myocardial damage [82].
One of the symptoms indicative of lung damage and pneumonia of viral genesis is the frosted glass effect in the lungs, determined by computed tomography (CT). The frosted glass effect is manifested on radiographs by areas of different shapes, sizes, number and location. The appearance of the frosted glass effect is a radiological sign of many different diseases, including viral infections, chronic lung diseases, fibrosis, other inflammatory conditions, oncological lesions of the lungs, so CT of the chest is not a method of verifying the diagnosis of COVID-19, but it should be noted that in COVID-19 the frosted glass effect also appears in the lower lobes of the lungs [66], and more often multiple involvement of the lung lobes is noted in the group of elderly people than in the group of young and middle-aged people [66].
FEATURES OF TREATMENT OF GERIATRIC PATIENTS WITH LUNG LESIONS CAUSED BY SARS-COV-2.
It is well known that comorbidities and polypragmasy have significant implications for older people, including in the treatment of lung disease caused by SARS-CoV2, which requires careful selection of the prescribed drug. It is known, for example, that antiretroviral drugs provoke liver damage and cause gastrointestinal disorders (nausea, diarrhoea), so the above group of drugs may be contraindicated in debilitated geriatric patients with concomitant liver pathology. A randomised open trial of lopinavir-ritonavir treatment in hospitalised patients with severe COVID-19 showed no clinical improvement or effect on mortality [71]. Remdesivir is a nucleoside triphosphate analogue with antiviral activity against a broad spectrum of human and zoonotic coronaviruses in both cell culture and mouse models, including SARS-CoV, MERS-CoV and SARS-CoV2 [12]. Remdesivir is administered only in hospitalised care and is contraindicated in patients with a glomerular filtration rate of less than 30 ml/min. Efficacy data from a multicentre cohort study showed that 36 out of 53 patients (68%) treated with the drug showed improvement in oxygenation parameters after the first dose of the drug, but the study was limited by a small number of patients, lack of randomisation and strict inclusion/exclusion criteria. In addition, 60% of patients developed side effects, including increased liver enzyme levels, diarrhoea, skin rash, renal dysfunction and development of renal impairment. Among the treatments given during the COVID-19 pandemic, chloroquine and hydroxychloroquine were widely used because their potential antiviral activity was suspected in addition to their anti-inflammatory effects [32; 73]. These drugs are relatively well tolerated by patients, but may cause rare but pronounced side effects. In addition, an analysis of a retrospective multicentre study confirmed a lack of significant benefit in hospitalised patients treated with hydroxychloroquine alone or in combination with azithromycin [29].
Corticosteroids, especially methylprednisone, have been used to counteract the inflammatory response in patients with COVID-19 and severe pneumonia and/or acute respiratory distress syndrome; however, in elderly patients, the benefits of these drugs are offset by emerging metabolic side effects that can exacerbate the course of pre-existing comorbidities such as arterial hypertension, diabetes mellitus, increased risk of fractures, development of psychiatric changes, and cataracts [69].
There are known publications that in patients with respiratory symptoms, inhalation of interferon in nebulised form causes cough relief, more pronounced in elderly patients than in young and middle-aged patients [21].
Tocilizumab, an IL-6 receptor antagonist, has been used in experimental animal studies [1] and in a small series of severe clinical cases in patients with COVID-19 [90]. In the experiment it was shown that tocilizumab, inhibiting the IL-6 receptor signalling pathway, does not provide an effective solution to reduce mortality from acute respiratory distress syndrome associated with the development of cytokine ‘storm’. In clinical settings, frequent complications have been reported after tocilizumab administration in patients over 65 years of age with diabetes mellitus: a high incidence of deep vein thrombosis and pulmonary embolism in COVID-19 patients is known [13; 42].
The use of anticoagulation therapy in geriatric patients with COVID-19 should be cautious. Evidence suggests that only in patients with D-dimer values above 3.0 μg/ml (six times the upper limit of normal) is anticoagulation therapy effective [77]; In addition, in COVID-19 patients treated with antiviral drugs, the plasma concentration of direct oral anticoagulants increased more than 6-fold during hospitalisation; therefore, the possibility of replacing direct oral anticoagulants with alternative parenteral antithrombotic drugs is being considered [8].
Interesting data have been obtained regarding the mechanism of virus entry into the macroorganism and the inverse association of infection with the intake of angiotensin-converting enzyme inhibitors (ACEIs), in particular, the role of angiotensin-2 receptor modulation has been studied [76; 40]. In other words, when taking IAPPs, a ‘busy flat phenomenon’ occurs, when the receptor, to which the virus should have joined, is occupied by a drug – a blocker of these receptors. It is known that elderly and old people often have high blood pressure figures, which are reduced by taking, among other things, IAPPs. International recommendations do not suggest cancelling the use of angiotensin-converting enzyme inhibitors and at this stage of knowledge about the specifics of infection caused by SARS-CoV-2 [87; 65; 24; 79].
PREVENTION OF SARS-COV-2 VIRUS INFECTION
A retrospective cohort study has confirmed the beneficial effect of angiotensin-converting enzyme inhibitors in limiting the possibility of acute respiratory viral infections, including SARS-CoV-2. The researchers’ conclusions are based on evidence of reduced all-cause mortality in patients regularly taking angiotensin-converting enzyme inhibitors and sartans [68].
Social distance as a prevention of SARS-CoV-2 infection remains important. Foreign researchers have reported high mortality rates in elderly and old people living in long-term care homes, where there is close social contact between residents and staff, which facilitates transmission [36] As of 14 April 2020, 40.2% of the 6773 patients who died in nursing homes in Italy had respiratory symptoms [54]. These closed collectives lacked sufficient medical staff to contain the epidemic [5]; personal protective equipment, tests to identify virus carriers or ill persons, guidelines for medical care to minimise the spread of infection, and insufficient available medication [38]. WHO has developed Guidelines for the management of patients in long-stay nursing homes [25], including . the need to develop a protocol for training and organisation of care for geriatric patients, ensuring quarantine rules for visits and social distancing, organising measures to contain the spread of infection, providing good palliative support if residents are infected. Particular importance is attached to the role of health professionals and carers in guaranteeing the physical, psychological and mental safety of people living in nursing homes [85]. In order to improve the performance of these structures and ensure high quality services, medical staff and social workers should have appropriate geriatric training.
Many papers show that restrictive measures have a negative impact on the elderly and old person, who feels abandoned, frightened and may not even be able to understand the situation or defend themselves – these problems are even more concerning for patients with pronounced cognitive deficits [10]. Isolation at home or in nursing homes causes negative changes in the habits of old people, cause fear, anxiety, loneliness, depression [81]; determines an altered perception of reality; disrupts sleep-wake rhythm; increases the likelihood of developing delusions [11]; increases the risk of suicide [26; 4].
CONCLUSIONS.
In summary, SARS-CoV-2-induced lung damage in elderly and old people has its own clinical, laboratory and biochemical features. Older individuals are particularly susceptible to unfavourable clinical outcomes when infected with SARS-CoV-2 virus. Elderly and old people with COVID-19 require an individualised approach taking into account age-related changes in the ageing body, existing polymorbidity, high risk of possible adverse adverse reactions in response to drug administration. At present, there is a lack of information on all the effects that may result from the development of COVID-19, especially in the elderly and old. The scattered studies available do not provide a complete clinical picture of the course and treatment of coronavirus infection in the elderly, but it is likely that subsequent studies will reveal the long-term consequences of this pandemic in pre-retirement and retirement age people as well
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