Many people are offering all kinds of solutions and suggestions, some bizarre and others more realistic. It must be said that the most effective measure[1] by which we can protect ourselves from the virus is to avoid being exposed to it. But how? Most importantly, through social distancing and hygiene measures.

Hygiene measures and (yes!) social distancing

A single millilitre of sputum can contain 100 million viral particles (viruses). Data from an endemic coronavirus strain (229E, not SARS-CoV-2, the new coronavirus) shows that it is resistant on surfaces and can remain infectious for at least 2 hours and even up to 9 hours on various materials. Available data on another very dangerous coronavirus (MERS, which was a threat in 2012) indicates that, at higher temperatures, the virus is less resistant, just as it is vulnerable to higher humidity compared to lower humidity.[2]

This means that we need to have very good hygiene of the hands, clothes, and surfaces that come in contact with our hands or body, as well as to avoid contact with other people. It is advisable to wash your hands regularly with soap and water or, if soap and water are not available (because you are not at home, for example), you should disinfect them with a hand sanitizer containing at least 60% alcohol. If you are not able to wash your hands, you must avoid touching your eyes, nose and mouth.[3]

Regarding discussions in the public space about the effectiveness of alcohol in removing the virus from surfaces, we must say that, yes, alcohol at a concentration of 62% is capable of eliminating the virus. Data available on other coronavirus strains shows that alcohol at concentrations ranging from 62% to 71%, oxygenated water at concentrations of 0.5% or sodium hypochlorite at 0.1% (popularly known as “chlorine water” or “chlorine solution”) are agents capable of removing the virus from object surfaces in approximately 1 minute. Interestingly, benzalkonium chloride at 0.05% concentrations or 0.02% chlorhexidine digluconate have lower efficacy and are not recommended.[4]

Despite authorities’ insistence on minimising social contacts, some citizens try to continue with life as we knew it—shopping, walking, playing in the park, relaxing in the park, organising weddings and celebrations. I’ve even witnessed people nudging those ahead of them in the checkout line at the supermarket (as if this will ensure a faster exit from the store!).

The fact that we think we are healthy is no guarantee that in the meantime we have not contacted the ultra-minuscule viral particle. There are patients who have contracted the virus but have no symptoms, and in this way can spread it. The fact that we know our friend, neighbor or colleague did not meet with anyone who has travelled to Italy or China is no guarantee that the virus could not have been contracted in the meantime through a known or unknown intermediary.

Data accumulated so far indicate that the virus is transmitted mainly through respiratory drops (aerosols from an infected person) and through direct contact.[5] Respiratory particles (mainly from sneezing or coughing) are a good way of transmission. It is known that coughing and sneezing are processes that generate aerosols, with a wide range of particle sizes that contain pathogens. Data from microbes and viruses (for example, the Ebola virus) indicate that they maintain their viability for at least 10 minutes in the air.[6]

It is therefore possible for someone to spread the virus in the air through a sneeze, and even after that person is gone, we may breathe those drops and become infected (or they might fall on our nose or face and, from there, be transmitted further by the touch of the hand). If an infected person squeezes into a crowded place, the probability of those tiny particles reaching others’ nasal mucosa is high. The bigger the crowd, the greater the likelihood of someone picking up these particles in the next seconds or minutes after a person coughs or sneezes (until they are scattered by the wind, air currents or fall under the action of gravitational force).

Public transport involves touching handles that were previously touched by a multitude of people. This could be an effective means of transmitting the virus, although this hypothesis has not been evaluated.

Does it make sense to boost your immunity?

This is a question that concerns many people in the current epidemiological context. The question does not have a simple answer, but a complex one. First of all, immunity is not a unique entity, capable of being strengthened or weakened under the action of any single external factor. The term “immunity” (from the Latin immunitas—legal protection for ancient Roman senators during the holding of public office) simply put, means the protection of the body against a disease—more precisely against an infectious disease. This protection is provided by a variety of cells and molecules that make up the immune system. When foreign substances or microorganisms are introduced into the body, the immune system organises a collective and coordinated response called an immune response.[7]

These days, when someone says “I need to increase my immunity”, they usually mean that they want to have better protection against infectious diseases, and believe that doing something like swallowing a pill or having a shot will make the immune system better able to organise an effective immune response. As the immune system is made up of a variety of cells and molecules (among which the most important are known as cytokines and chemokines), it can be influenced specifically or non-specifically in a variety of ways.

There are drugs capable of inducing a very specific and very effective immune response for a particular infectious agent; they have a high degree of safety and are generically called vaccines.[8]Unfortunately, a vaccine for the new coronavirus is not yet available.

Natural products, such as some probiotics and prebiotics, plant products (Echinacea), and some vitamins (C, D and others) have been associated with a role (usually modest but possibly useful) in protecting or stimulating some of the immune response mechanisms.[9] Before we rush to use them, however, we should ask ourselves another key question: Is increased immunity (greater than normal responsiveness) necessary to be able to cope with SARS-CoV-2 infection?

So far things have not been very clear. In recent medical literature, based on experience from China and Italy, it has been suggested that an immune system under immunosuppression does not pose a greater risk of severe infection with the new coronavirus than a healthy immune system. In general, immunosuppressive drugs tend to increase the risk of severe infections caused by viral agents, such as adenoviruses, rhinoviruses, noroviruses, influenza virus, etc. With the coronavirus infection, some voices say that this is not the case.

Lorenzo D’Antiga, an Italian doctor from Bergamo, who specialises in hepatology, gastroenterology and paediatric transplantation, states in a very recent article: “Many of these viruses, including Coronaviruses, implicate the host response as an important contributor to the disease process; in this respect dysregulated and excessive innate immune responses appear particularly important drivers of tissue damage during infection. It has been postulated that the reason why bats are the natural, healthy reservoir of these viruses may reside in their immune tolerance.”[10] That is, the bat’s immune system does not react to the virus. In other words, contrary to our expectations that a feisty immune system is needed in order to deal with viruses, in bats a lazy immune system is what allows them to keep the virus in the body without getting sick. Indeed, experimentally induced infections in bats with viruses carried by these flying mammals have shown that bats form few antibodies in response, and even the antibodies that are formed disappear rapidly.[11]

Therefore, the key aspect that seems to allow the bats to cope well with the presence of the new coronavirus is not a very aggressive immune system, but rather an inactive one. These observations suggest that it may not be necessary to stimulate the immune system.

Children, especially those under the age of 12, are just developing their immune system, which is less experienced and therefore, theoretically, children have lower immunity. Consequently, we should expect them to become easier victims of the virus. Lorenzo D’Antiga mentions that in the case of the 2002 outbreak of SARS (another condition caused by a coronavirus), of the 48 children under the age of 12 who were diagnosed with the condition, most of them had mild symptoms (fever, cough, runny nose) and none required oxygen supplementation. In general, children with SARS had no symptoms other than those of other common respiratory viruses and, although transplant patients would have been expected to have rather bleak outcomes, no such cases were reported after the outbreak.[12]

Why would transplant patients be expected to have more sombre outcomes? Because these patients systematically receive immunosuppressive medication; that is, they have a lower level of immunity. We must note that this argument may not be very relevant, as it is possible that the transplant patients may have taken additional protective measures during that period in order to avoid infection (better isolation, additional disinfection measures, etc.).

Similarly, D’Antiga argues, in the case of MERS (Middle East Respiratory Syndrome, a respiratory syndrome caused by a camel’s coronavirus, which emerged in 2012), the main risk factors were age, male sex and the presence of comorbidities (obesity, diabetes, heart disease, lung disease, kidney disease, smoking)—exactly the same risk factors observed in COVID-19. However, the immunosuppressed status was not identified as a risk factor in publicly available data[13], argues the Italian doctor.

One of D’Antiga’s arguments is that, statistically, transplanted patients were not among the victims of previous dangerous coronaviruses (SARS, MERS). However, it must be mentioned that, in fact, there have been several cases of transplant patients who have subsequently been infected with the MERS coronavirus. In a series of three such cases reported by doctors in South Korea, one patient was asymptomatic (which tends to confirm the Italian doctor’s statement), a 49-year-old patient also had a co-infection with Mycobacterium tuberculosis and eventually died, and a third patient appears to have survived, although the symptoms were prolonged (and immunosuppressive corticosteroids contributed to the control of the symptoms)[14]. In the USA, two cases were also reported in renal transplant patients, one of whom died aged 44 (the authors suggested his death was related to acute renal failure) and a second 30-year-old patient who survived. The reports mentioned that the natural history of the infection “seems to be similar to that of the non-transplanted population, based on the variable clinical presentation of these two cases.”[15] These cases show that transplanted patients, who have an immune system operating at lower parameters, do not appear to have developed more severe or clinically different forms of the disease when compared to immunocompetent patients.

In 2015, one patient (MERS) managed to get in close contact with 175 other people, 26 of whom were infected. Chinese researchers have been trying to find out what the risk factors were that caused some people to become infected and not others. They reported that the risk of infection of patients with autologous stem cell transplantation (bone marrow transplantation from the patient’s own bones) was actually much higher in infected patients than in uninfected persons. However, this very high risk is based on data from two patients in the infected group, compared to a single patient in the uninfected group. The risk could be even higher, but not necessarily related to immunosuppression, because among the uninfected people there were also three people with solid organ transplants (in other words, although the virus spreader came in contact with three transplant receivers, under immunosuppression, none became ill with MERS). Also, the proportion of cancer patients (who, because of the treatments they receive, frequently have lower immunity) was not higher among the infected patients compared to the non-infected patients.[16]

Dr. D’Antiga recounts the preliminary experience in Bergamo, where, out of about 200 transplant recipients at his centre, including 10 patients currently admitted, none developed clinically obvious lung disease, despite the fact that three tested positive for SARS-CoV-2 (COVID-19). He also adds that, given that the infection is currently endemic in the Bergamo area, other children are likely to carry the virus, but none with pneumonia were reported to the clinic or via the daily telephone consultation provided by the hospital.[17] In other words, the lower immunity of these transplant children did not predispose them to becoming victims of COVID-19.

Recently a group of researchers in China reported the case of a kidney transplant patient (transplanted 12 years ago) undergoing immunosuppressive therapy, who developed COVID-19-induced pneumonia. The 52-year-old man presented general clinical characteristics very similar to those of the non-transplant patients and, following a treatment with a lower dose of an immunosuppressant (the same immunosuppressive drug he used previously) and a low dose of methylprednisolone (which has immunosuppressive effects) he made a full recovery.[18]

A group of six British researchers, writing on behalf of the HLH Across Specialty Collaboration (UK) in the prestigious medical publication The Lancet, points out that respiratory distress syndrome is the leading cause of COVID-19 mortality and links it to secondary hemophagocytic lymphohistiocytosis (LHHs). Although a very rare disease in adults, they say, LHHs are most commonly triggered by viral infections and are characterised by non-relapsing fever, cytopenia (decreased number of mature, normal blood cells), hyperferritinemia (exaggerated ferritin level, a protein whose role is to store iron inside cells); in about half of the patients there is pulmonary involvement, including respiratory distress syndrome.[19]

For those familiar with the manifestations of COVID-19, the LHHs emulate them surprisingly well. Multiple publications (at least 10 medical articles) mention that patients with severe forms of COVID-19 experienced a syndrome of “cytokine storm” type, which is characterised by an increase in the blood concentration of many cytokines[20],[21],[22],[23](in very simplified language: an exaggerated immune reaction, manifested by the exaggerated secretion of certain molecules that are part of the immune system).[24] Analysis of 150 cases of COVID-19 in Wuhan indicates that survivors had significantly lower levels of ferritin (mean 614.0 ng/ml) than those who died (mean 1297.6 ng/ml)[25] and IL-6[26], which suggests that mortality may be caused by virus-induced hyperinflation.[27]

In this context, the six British researchers point out that, although corticosteroids are not routinely recommended in SARS and MERS, because they could exacerbate COVID-19-associated lung injury “in hyperinflation immunosuppression they seem likely to be beneficial.” Therefore, the recommendation of these authors is to evaluate all patients with severe forms of COVID-19 to identify the subgroup of patients whose immunosuppression could reduce mortality, for which they recommend considering several possible classes of drugs (steroids, intravenous immunoglobulin, selective blocking of certain interleukins, or blocking JAK).

A group of virologists in China also believes that in cases of pneumonia caused by SARS-CoV-2, it is important to stop cytokine production and the inflammatory response. However, they recognise that such a strategy is challenging because we do not yet know which features of the immune system can be specifically inhibited, without compromising the beneficial immunity of the patient. In this regard, they speculate that there are several specific immune system molecules that could be blocked, for example the production of free radicals or some interleukins (IL-1, IL-4, IL-6, IL-8, IL-21 ).[28]

Now that we have summarised what we know about severe cases of COVID-19 and immunity, we should try to answer the initial question. Yes, it seems to make sense to have good, normal immunity to deal with SARS-CoV-2 infection. However, a slightly lower level of immunity does not appear to make a difference, from the available data. Therefore, not having access to Vitamin C or Vitamin D is unlikely to make you especially at risk of being infected by COVID-19. Conversely, if you have access to and use Vitamin C, Vitamin D or any other remedy used to boost immunity, do not consider yourself invulnerable. And if you find out that a loved one has a serious form of COVID-19, and doctors use an immunosuppressive drug (or more of those), do not be surprised. Trust that they are doing everything they can, in light of the current medical data, to cure them.

Robert Ancuceanu, PhD, is a professor in the Faculty of Pharmacy at the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania.

The original article was published on this web page.

Footnotes

[1]„S. P. Adhikari, S. Meng, Y.-J. Wu, et al., «Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review», in Infectious Diseases of Poverty, vol. 9, no. 1, p. 29, 

[2]„G. Kampf, «Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents», in Infection Prevention in Practice, vol. 2, no. 2, 2020, 

[3]„S. P. Adhikari, S. Meng, Y.-J. Wu, et al., art. cit.”

[4]„G. Kampf, art. cit.”

[5]„Y.-C. Wu, C.-S. Chen, Y.-J. Chan, «The outbreak of COVID-19: An overview», in Journal of the Chinese Medical Association, no. 83, no. 3, 2020, p. 217-220, 

[6]„Rachel M. Jones, Lisa M. Brosseau, «Aerosol transmission of infectious disease», in Journal of Occupational and Environmental Medicine, vol. 57, no. 15, mai 2015, p. 501-508, 

[7]„A. K. Abbas, A. H. Lichtman, S. Pillai, Cellular and molecular immunology, Saunders/Elsevier, Philadelphia, 2012.”

[8]„A. Saul, K. L. O’Brien, «Prioritizing vaccines for developing world diseases», in Vaccine, no. 35, Supl. 1, 2017, p. A16-A19, 

[9]„Michael J. Parnham, Frans P. Nijkamp, Adriano Rossi (editori), Nijkamp and Parnham’s Principles of Immunopharmacology, Springer International Publishing, Cham, 2019.”

[10]„Lorenzo D’Antiga, «Coronaviruses and immunosuppressed patients. The facts during the third epidemic», Liver Transplant, 20 mar. 2020, 

[11]„J. N. Mandl, C. Schneider, D. S. Schneider, M.L. Baker, «Going to Bat(s) for Studies of Disease Tolerance», in Frontiers in Immunology, no. 9, 2018, p. 2112, 

[12]„Lorenzo D’Antiga, art. cit.”

[13]„D. S. Hui, E. I. Azhar et al., «Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission», in Lancet Infectious Diseases, no. 18, no. 8, aug. 2018, p. e217-e227, pubmed.ncbi.nlm.nih.gov/29680581/”.

[14]„S.-H. Kim, J.-H. Ko, G. E. Park et al., «Atypical presentations of MERS-CoV infection in immunocompromised hosts», in Journal of Infection and Chemotherapy, vol. 23, no. 11, 23 mai 2017, p. 769-773, www.jiac-j.com/article/S1341-321X(17)30089-2/fulltext”.

[15]„M. AlGhamdi, F. Mushtaq, N. Awn, S. Shalhoub, «MERS CoV infection in two renal transplant recipients: case report», in American Journal of Transplantation, vol. 15, no. 4, 2015, p. 1101-1104, onlinelibrary.wiley.com/doi/full/10.1111/ajt.13085”.

[16]„J. H. Ko, H. Seok, G.E. Park et al., «Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak», Journal of Infection and Chemotherapy, vol. 24, no. 2, febr. 2018, p. 150-152, 

[17], „Lorenzo D’Antiga, art. cit.”

[18]„L. Zhu, X. Xu, K. Ma et al., «Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression», in American Journal of Transplantation, 17 mar. 2020, 

[19]„P. Mehta, D. F. McAuley, M. Brown et al., HLH Across Speciality Collaboration, UK, «COVID-19: consider cytokine storm syndromes and immunosuppression», Lancet, 13 mar. 2020, 

[20]„Such as TNF-α, IL-1, IL-6 (see notes 2-4), IL-2 (see note 4), IL-10, GCSF (granulocyte colony stimulating factor), IP10 (protein inducible protein) Interferon γ, MCP1 (chemo-attractive monocyte protein), MIP1A (macrophage inflammatory protein 1α), and TNF α (tumor necrosis alpha factor).”

[21]„C. Qin, L. Zhou et al., «Dysregulation of immune response in patients with COVID-19 in Wuhan, China», în Clinical Infectious Deseases, 12 mar. 2020, 

[22]„P. Conti, G.Ronconi, A. Caraffa et al., «Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies», in Journal of Biological Regulators and Homostatic Agents, vol. 34, no. 2, 2020, 

[23]„L. Chen, H. G. Liu, W. Liu et al., «Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia», Zhonghua Jie He He Hu Xi Za Zhi, no. 43, no. 3, 12 mar. 2020, p. 219-222, 

[24]„P. Mehta, D. F. McAuley, M. Brown et al., art. cit.”

[25]„Ferritin is not mentioned in the main text of the article, but in the supplementary material available online.”

[26]„Q. Ruan, K. Yang, W. Wang et al., «Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China», in Intensive Care Medicine, 3 mar. 2020, 

[27], „P. Mehta, D. F. McAuley, M. Brown et al., art. cit.”

[28]„G. Li, Y. Fan, Y. Lai et al., «Coronavirus infections and immune responses», in Journal of Medical Virology, vol. 29, no. 4, 2020, p. 424-432, onlinelibrary.wiley.com/doi/full/10.1002/jmv.25685