key: cord-0865373-bqhml1yo authors: Chowdhury, Mohammad Asaduzzaman; Hossain, Nayem; Kashem, Mohammod Abul; Shahid, Md. Abdus; Alam, Ashraful title: Immune Response in COVID-19: A Review date: 2020-07-14 journal: J Infect Public Health DOI: 10.1016/j.jiph.2020.07.001 sha: d98e72abba83071865797d85a95330b4f40b6c58 doc_id: 865373 cord_uid: bqhml1yo The immune system protects us from viruses and diseases. It produces an antibody to kill pathogen. This review shows a brief picture about the immune system to protect us from COVID-19. It illustrates the process of the immune system, how it works, and mechanism of the immune system to fight virus. It also provides information on recent COVID-19 treatment and experimental data. Various types of potential challenges are also discussed for the immunes system. At the end, some foods have been suggested and some are discouraged. Physical exercise is also encouraged. This article can be used as a state of the art at this critical moment to the globe for a promising alternative solutions related to the survival of people from coronavirus. The earth is relaxing but human is dying. As of 18 th April 2020, more than 154,000 people were newly identified coronavirus with zoonotic origin in the genus Beta coronavirus [1] . China, at the end of 2019. People are being affected by human to human transmission due to close contact [2] [3] and people affected by COVID-19 suffer from severe respiratory illness [4] . People who are elderly and have numerous comorbidities are the most vulnerable to this virus [5] [6] . Although there is no registered treatment or vaccine for this disease [7] Our whole body consists of the organs of the immune system ( Figure 1 ) to protect against diseases [9-10]. It plays a key role to maintain health and pathogenesis. It also protects our body from harmful substances, germs and cell changes (neoplasm) [11] .The key player in the immune system is the white blood cells (WBC)which can travel throughout the body using the blood vessels. To monitor for invading microbes, our body exchanges cells and fluids between blood and lymphatic vessels and enables the lymphatic system. The lymphatic vessels carry lymph. Each lymph node contains specialized compartments where they can encounter antigens. Through the incoming lymphatic vessels, the immune cells and foreign particles enter the lymph nodes. When they are in the bloodstream, they are transported to tissues throughout the body. They continue the cycle all over through patrolling for foreign antigens everywhere and then gradually drift back into the lymphatic system. The immune cells gather, work, and serve to confront antigens in lymph nodes and spleen's compartments [12] . J o u r n a l P r e -p r o o f COVID-19 is an RNA virus with a crown like appearance. Its diameter is approximately 60-140 nm. On one side, it has a concave surface with a ridge. It makes a larger binding interface ad well as more contacts with ACE2. It can make better contact with the Nterminal helix of ACE2 and have higher affinity [13] . It is transmitted through respiratory droplets from coughing and sneezing. It enters our nasal system by inhaling and starts replicating. ACE2 is the main receptor for the COVID-19 virus [14] . The spike protein present on the surface of COVID-19 gets pinched inside the host cell binding to the ACE2 receptor. Here, the enzyme furin present in the host cell plays a vital role for the virus to enter, which was absent in SARS-CoV [15] .Then the virus starts to propagate with limited innate immune response and can be detected by nasal swabs. The virus then propagates and reaches the respiratory tract. There it faces a more robust innate immune response. At this stage, the disease is clinically manifest and an innate response cytokine may be predictive of the subsequent clinical course [16] . For beta and lambda infections, viral infected epithelial cells are a major source [17] . The disease will be mild for 80% of the infected patients and mostly restricted to the upper and conducting airways [18] . With conservative symptomatic therapy, these individuals may be monitored and monitored at home. Around 20% of the infected patients will develop pulmonary infiltrates and some of these will develop very severe disease [19] . The mortality rate of severe COVID-19 patients can be as high as 49% showed by a recent epidemiological by China CDC [20] . From Wuhan, 292 COVID-19 patients were studied there. Age was the risk factor of severe patients shown by the Lasso algorithm. When the age of severe patients increased by 5, years, the risk increased by 15.15%. Most of the patients with COVD-19 were elderly patients in the severe group with basic diseases. Chronic obstructive pulmonary disease, hypertension, malignant tumor, coronary heart disease, and chronic kidney disease were more frequent in the severe group than in the mild group. From 145 severe cases, 51 patients died, accounting for 34.69% and 90.2% dead patients are over 60 years old. 40 patients had basic disease out of 51 deaths, accounting for 78.43%. Recent reports show that patients with more than 60 years of age and having comorbidities, especially hypertension are believed to be risk factors for severe disease and death from SARS-CoV-2 infection [21] [22] [23] . As there is no registered medicine or vaccine against COVID-19, our immune system is the best defense. The immunity system supports our body's natural ability to defend against pathogens which include viruses, bacteria, fungi, protozoan, and worms [24-25], resist infections. As long as the immune system runs smoothly, we do not notice infections like COVID-19. Our immune system can be categorized into three categories. They are, namely, innate immunity (rapid response), adaptive immunity (slow response), and passive immunity ( Figure 2 ). Passive immunity is again two types and they are natural immunity which we receive from our mother and artificial immunity that we receive from medicine. Skin and inflammatory response begins when our body is affected [26] [27] . However, when our body encounters any germs or viruses for the first time, the immune system cannot work properly and we become sick. The same thing has happened in the case of COVID-19 [28] . According to Yufang Shi et al. [34] overall, the synopsis is based on some clinical common sense. They proposed some normal approaches to the treatment of COVID-19 patients ( Figure 5 ). They believed that the two-phase immune defense-based protective phase and inflammation-driven damaging phase division are essential. During the first, Doctors should try to boost immune response and in the second phase suppressing it. Vitamin B3 should be used just after the coughing begins as it is highly lung protective. When breathing difficulty starts, hyaluronidase can be given intratracheally and at the same time 4-MU can be used to inhibit HAS2. Clearly, susceptibility information will be provided by HLA typing for strategizing prevention, treatment, vaccination, and clinical approaches. J o u r n a l P r e -p r o o f The leading cause for mortality of COVID-19 patients is respiratory failure from acute respiratory distress syndrome [35] . Secondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by fulminant and fatal hypercytokinaemia with multiorgan failure and it is under recognized. Viral infection triggers sHLH and occurs in 3·7-4·3% of sepsis cases in adults [36] [37] . sHLH, resembled by a cytokine profile, is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, interferon-γ inducible protein 10, granulocyte-colony stimulating factor, macrophage inflammatory protein 1-α, monocyte chemoattractant protein 1, and tumour necrosis factor-α (TNF-α) [38] . A recent retrospective fatality predictor's multicenter study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin and IL-6, suggesting that mortality might because of virally driven hyper inflammation [39] . Research is going on around the world to develop a vaccine against COVID-19. According to report [40] , 115 The researchers are researching to improve the immune system against COVID-19 and here some of the data are reviewed. 10 proteins are encoded by COVID-19 genome. One of them is the spike protein (S-protein) mentioned as a glycoprotein exists in the virus infected region (Figure 6 ). The S-protein is a significant therapeutic target, ensured its location, and targetable using antibodies [93] . The formation of neutralizing antibodies immunization of animals with S-protein oriented vaccines is very effective in preventing infection by homologous coronavirus [94] . In a research at the University of Copenhagen, researchers used net MHC to make in silicon predictions of epitopes presented by 11 MHC-1 alleles that covered approx. 90% of the [105] As of 13 March 2020, outside China, there were 32 countries with more than 100 COVID-19 cases [104] . The highest number of infections was found in seven countries and they were: the United States (n=2294), France (n=3671), Germany (n=3675), Spain (n=5232), Korea (n=8086), Iran (n=11,364), and Italy (n=17,660). The number of J o u r n a l P r e -p r o o f confirmed cases in other countries 25 countries has been found less than 1200 [105] . The related data is noted in Table 3 . The change of R0 and Rt is connected to the proportion of individuals those have immunity in their body to that pathogen in that population. The alternative method of estimating Rt for a pathogen including the population is by multiplying R0 through the proportion of that population those are considered non-immune to that pathogen. In this perception, R0 will only similar level of Rt if there are no immune persons in the population. It indicates that any partial pre-existing immunity to the infecting elements is able to decrease the number of expected secondary cases emerging. Whenever this perception is applied in case of herd immunity to control the COVID-19 epidemic, the fatality rate of corona virus is in the range between 0.25-3.0% of the estimated population, the measured number of people who may die from affecting this virus, but when the population attains the Pcrit herd immunity level, can be difficult to accept. Estimates of effective reproduction number (Rt) (95% CI), (n = 32) Minimum proportion (%) of total population required to recover from COVID-19 to confer immunity (Pcrit) Ling, Ni et al. [106] experimented patients with various methods. Initially they used sera but no According to the World Health Organization, healthy foods as well as hydration are vital. People consuming a well balanced diet are healthier with a strong immune system and have less risk of chronic illness, infectious diseases. The importance of vitamin and mineral is vital. Vitamin B, which is insoluble in water, protects from infection. Vitamin C protects us from flu like symptoms [112] . Lack of vitamin D and E can lead us to infection of coronavirus [113] but vitamin D can be found in sunlight and vitamin E can be found in oil, seeds, fruits, etc. Lack of iron and excess iron can lead to risk [114] [115] . Zinc is necessary for maintaining our immune system [116] . Food rich in protein should be on the top priority because it has immune properties (immunoglobulin production) and potential antiviral activity [117] [118] [119] . Therefore, in regular meal, people should eat fruits, vegetables, legumes, nuts, whole grains, and foods from animal sources (Figure 9 ). Food found from plant containing vitamin A should be consumed. 8-10 cups of water should be drunk every J o u r n a l P r e -p r o o f day. Malnutrition is dangerous for COVID-19 patients and proper nutrition should be provided [120] [121] . Fruit juice, tea, and coffee can also be consumed. Much caffeine, sweetened fruit juices, fruit juice concentrates, syrups, fizzy, and still drinks must be avoided. Unsaturated fats, white meats, and fish containing low fat are advised to consume. Saturated fat, red meat, more than 5g salt per day, and industry processed food should be avoided [122] . Along with diet, physical activity is another factor. People should be active and do physical exercise regularly to boost the immune system and should have proper sleep [123] . Although there is no registered medicine for COVID-19 treatment but hydroxychloroquine and remdesivir are prescribed which are partially effective [124]. This review on boosting up the immunity system appears a potential resource for the treatment of COVID-19 patients. The process and mechanism of immunity system can be a good source of knowledge for immunity system development. Recent observations for COVID-19 treatment can be focused on. If potential challenges can be overcome, it can be a great J o u r n a l P r e -p r o o f achievement. Finally, the suggested food should be consumed to boost up the immunity system as there is no registered medicine for COVID-19 treatment. The authors declared that there is no any conflict of interest Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak -an update on the status Early transmission dynamics in Wuhan, China, of novel coronavirus infected pneumonia Clinical Characteristics of Coronavirus Disease 2019 in China Herd immunityestimating the level required to halt the COVID-19 epidemics in affected countries Potential interventions for novel coronavirus in China: A systematic review Structural basis of receptor recognition by SARS-CoV-2 Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS Structure, Function, and antigenicity of the SARS-CoV-2 spike glycoprotein Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome Transcriptome analysis of infected and bystander type 2 alveolar epithelial cells during influenza A virus infection reveals in vivo Wnt pathway downregulation Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention Pathogenesis of COVID-19 from a cell biology perspective Clinical Characteristics of 138 Hospitalized PatientsWith 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Analysis of Risk Factors of Severe COVID-19 Patients Assessing the human immune system through blood transcriptomics Host Immune Response and Immunobiology of Human SARS-CoV-2 Infection Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic COVID-19: Immunology and treatment options COVID-19 infection: the perspectives on immune responses Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China Adult haemophagocytic syndrome Macrophage activation-like syndrome: a distinct entity leading to early death in sepsis Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China COVID-16: consider cytokine storm syndromes and immunosuppression The COVID-19 vaccine development landscape The starting line for the COVID-19 vaccine development Treatment with convalescent plasma for COVID-19 patients in Wuhan, China The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta -analysis Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS Transcriptome analysis of infected and bystander type 2 alveolar epithelial cells during influenza A virus infection reveals in vivo Wnt pathway downregulation Convalescent plasma in Covid-19: Possible mechanisms of action Treatment With Convalescent Plasma for Critically Ill Patients With SARS-CoV-2 Infection Chest Treatment of 5 critically ill patients with Covid-19 with convalescent plasma Effectiveness of convalescent plasma therapy in severe COVID-19 patients Treatment with convalescent plasma for COVID-19 patients in Wuhan, China Use of convalescent plasma therapy in two COVID-19 patients with acute respiratory distress syndrome in Korea Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients Use of convalescent plasma therapy in SARS patients in Hong Kong Advances in clinical diagnosis and treatment of severe acute respiratory syndrome World Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital Epidemiologic features, clinical diagnosis and therapy of first cluster of patients with severe acute respiratory syndrome in Beijing area Treatment of severe acute respiratory syndrome with convalescent plasma Hong Kong Challenges of convalescent plasma infusion therapy in Middle East respiratory infection: A single centre experience Evaluation of convalescent plasma for Ebola virus disease in Guinea Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection Hong Kong's experience on the use of extracorporeal membrane oxygenation for the treatment of influenza A (H1N1) Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China Successful treatment of avian influenza with convalescent plasma Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses Antimalarial drugs in the treatment of rheumatological diseases Arbidol: a broad-spectrum antiviral compound that blocks viral fusion Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase Oral oseltamivir treatment of influenza in children An Update on Current Therapeutic Drugs Treating COVID-19 SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease receptor Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Medication for COVID-19 -an overview of approaches currently under study In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clin Hydroxychloroquine and azithromycin as a tratment of COVID-19: results of an open-label non-randomized clinical trial Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses Randomized controlled trial of Ebola virus disease therapeutics Compassionate use of remdesivir for patients with severe COVID-19 Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset A trial of lopinavirritonavir in adults hospitalized with severe Covid-19 Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China Arbidol combined with LPV/r versus LPV/r alone against corona virus disease 2019: a retrospective cohort study Experimental treatment with favipiravir for Ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea Candidate drugs against SARS-CoV-2 and COVID-19 An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice ProMED-mailCOVID-19 update (39): global, more countries, stability, mitigation impact WHO (2020) Archive No Herd immunity -estimating the level required to halt the COVID-19 epidemics in affected countries Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2 Basic Immunology: Functions and Disorders of the Immune System The Compatibility Gene. London: Penguin The Emperor of All Maladies: a Biography of Cancer The Immune System Nutrients and their role in host resistance to infection Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitaminreplete preruminant calves Crossing the Iron Gate: why and how transferrin receptors mediate viral entry Childhood iron deficiency anemia leads to recurrent respiratory tract infections and gastroenteritis Zinc and immunity: an essential interrelation A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) Immunomodulatory properties of milk Antiviral activities of whey proteins Prognostic impact of diseaserelated malnutrition Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial How to boost your immune system during the COVID-19 pandemic