Letter to the Editor: Kim, S.-W., Su, K.-P. (2020) Using psychoneuroimmunity against COVID-19, Brain, Behavior, and Immunity (2020), doi: https://doi.org/10.1016/j.bbi.2020.03.025.

To the Editor,

We read the recent article by Kim & Su with great interest. This article was strongly focused on the importance of psycho-neuro-immune networks in the fight against the ongoing pandemic caused by Sars-CoV-2. Several crucial aspects of the COVID-19 pandemic were highlighted, including the impact of the pandemic on the populations of the world’s richest and most technologically advanced nations, which are experiencing unprecedented conditions of widespread mortality, fear, and social isolation.

A recent survey conducted on the Italian population during the pandemic showed there is a widespread state of psychological distress among them (i.e. anxiety, depression, sleep disorders and more), as confirmed in other survey involving three Europe countries: Italy, Spain and United Kingdom (see Table 1 ). The latter survey shows higher level of depression in italian population than the former, probably due to the more specific investigation methods.

Table 1

Stress index score variation among adult population before and after the announcement of the nationwide lockdown in Italy*
Stress Index score	Date of detection: 3/2/20	Date of detection:3/9/20	Date of detection: 4/6/20
High	27%	43%	41%
Medium	45%	45%	38%
Low	28%	12%	21%
Main forms of psychological distress**
Psychological distress	Total	Men	Women
Stress/Anxiety	42%	40%	43%
Sleep disorders	24%	19%	28%
Irritability	22%	21%	22%
Depressed mood	18%	15%	21%
Eating problems	10%	10%	10%
Problem in relationships	7%	6%	8%
Problem with partner	3%	5%	5%
Problem with sons	1%	5%	1%
None	28%	31%	25%
Percentage of depressed subjects during the pandemic among adult population in Italy, Spain and United Kingdom***
Total	Italy	Spain	United Kingdom
61%	59%	67%	57%

The survey was carried out by the Piepoli Institute for the National Council of the Order of Psychologists (8 April 2020) on a total sample of 501 subjects representative of the Italian population. On 9 March 2020, the government of Italy extended lockdown to entire country: this has raised the stress index national trend towards the higher scores and it remained high after one month.

The survey was carried out by the Piepoli Institute for the National Council of the Order of Psychologists (8 April 2020) on a total sample of 501 individuals representative of the Italian population divided by gender.

The survey was carried out by the Open Evidence, a spin-off of Universitat Oberta de Catalunya (UOC), realized with the contribution of BDI- Schlesinger Group and Università degli Studi di Milano, Universitat Oberta de Catalunya, Universidad Nacional de Colombia, Università di Trento, University of Glasgow, on a total sample of 1.000 subjects divided by countries involved in the survey. The percentages refer to those who reported to have been depressed in the last 7 days (reference period: from 4/24/2020 to 5/1/2020). DASS-21 (Depression, Anxiety and Stress Scale – 21 Items) and SASRQ (Stanford Acute Stress Reaction Questionnaire) were used to quantify Depressive symptoms.

Moreover, predictive analyses showed that mental health of a large proportion of the population in Italy, United Kingdom and Spain is at high risk for stress, anxiety and depression (41%, 42% and 46% respectively), due to socio-economic vulnerability and worsened conditions since the pandemic onset (Open Evidence, 2020).

We believe that this mental condition could plausibly weaken the resistance of individuals and the population to SARS-CoV-2 infection. In these conditions of uncertainty, prevention strategies and early intervention for infected patients in primary care settings appear to be crucial for tackling the pandemic. This requires a profound change in our approach to the prevention and treatment of the infection, based on the integration of the biomedical and psychological sciences and professions to promote resilience in the general population.

The vast majority of the population appears to actually possess the endogenous resources needed to fight infection by SARS-CoV-2, especially when the infection is silent or occurs with few symptoms. We believe that a rational approach based on psychoneuroendocrineimmunology (PNEI), the paradigm built on the two-way relationship between the psychological and biological systems in environmental and social contexts (Ader, 2007, Bottaccioli and Bottaccioli, 2020), could provide an appropriate model for the identification of risk and resilience factors in the context of SARS-CoV-2 infection. The PNEI model could also help provide a comprehensive understanding of the effects of infection on the whole health status of patients, including their mental state and psychopathological disturbances (Bottaccioli et al., 2019).

A balanced immune response to SARS-CoV-2 infection is the central target of efforts to promote resistance and resilience to infection. In the early phase of the disease, there is a high neutrophil:lymphocyte ratio, overproduction of IL-1β and IL-6 cytokynes, and, in contrast, low production of IFN-γ (Chen et al., 2020).

A number of factors can regulate or unbalance the immune system’s antiviral response, including diet, physical activity, stress, and mental state.

The clinical features of critically ill COVID-19 patients include widespread malnutrition. Malnourished COVID-19 patients in intensive care and sub-intensive care are associated with higher hospitalisation costs, prolonged stays, and increased mortality. Therefore, the early initiation of nutritional therapy is vital, particularly in patients with organ failure and sepsis, and could significantly change the course of the disease even in non-critical patients hospitalised in ordinary wards or treated at home (Liang, 2020).

One of the main effects of forced quarantine during a pandemic is reduced mobility. Although all members of the population may suffer from a prolonged period of almost total physical inactivity, the elderly population may, once again, pay the highest price. In the elderly, inactivity rapidly depletes muscle reserves and accelerates bone turnover, promoting sarcopenia; it also worsens respiratory function, alters metabolism, and impairs blood pressure regulation. Regular physical activity is also a trophic stimulus for the brain (Jiménez-Pavón et al., 2020).

Depression can be seen as a form of low-grade inflammation (Pariante, 2017) that is particularly active in the brain circuits involved in adaptive behaviour and processing emotional states. This leads to a pathological condition that is continuously fed by inadequate lifestyle behaviours that, in turn, support the inflammatory state and worsen the patient’s psychological state (Gialluisi et al., 2020).

Treating distress helps fight inflammation (Bower and Irwin, 2016) and can thus, also be a resource in the fight against the COVID-19 pandemic. However, there is currently widespread difficulty in launching a strategy capable of articulating and integrating psychological intervention into health care and society. This difficulty is due to both the forced priority given to medical assistance emergencies in the first phase and, above all, due to a widespread cultural problem that tends to separate psychological aspects from health-related issues and health interventions in general. A cultural problem that does not seem to concern the Italian population which, on the contrary, is very favourable to a greater presence of psychologists in primary care services (i.e. hospitals, nursing homes, social services, family physicians’ offices) in order to counteract the COVID 19 pandemic effects (Piepoli Institute, 20 April 2020, data being published).

If implemented, the large-scale integration of medicine and psychology would provide a formidable new impetus for improving human health care, even during this threatening time.