Post-COVID Complications: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Virology
Contributor: , , , , , ,

Millions of people suffered badly due to COVID as well as post-COVID lung infections that were hard to comprehend. It is evident from numerous case studies that many COVID-19 patients who are released from nursing homes or hospitals are more prone to developing multi-organ dysfunction than the general population. Understanding the pathophysiology of COVID-19 and its impact on various organ systems is crucial for developing effective treatment strategies and managing long-term health consequences. 

  • COVID-19
  • long COVID
  • pandemic
  • lung disease
  • heart disease

1. Short-Term Health Issues

The short-term or immediate health issues include fever (moderate to high), shortness of breath, cough, chestpain, jointpain, nausea, diarrhea, sore throat, fatigue, rashes on the skin, headache, loss of odor or taste, conjunctivitis, and a tendency towards acute respiratory distress syndrome (ARDS) [26]. These are some clinical consequences encountered by the patients once they are infected. If the patient has mild symptoms, no hospitalization is required. Home isolation, proper food, and medication are sufficient for the patient’s recovery. When the symptoms are severe, especially when the patient has acute pneumonia, he or she needs hospitalization. However, post-COVID complications may arise in both of these groups; the ones with mild symptoms and the ones with acute symptoms [27].
According to recent studies, COVID-19 affects women less frequently than it does men [28]. This can be understood in terms of sex hormones, which are very important for controlling how the immune system responds to viruses. The major sex hormones are namely progesterone, oestrogen, and testosterone [29]. Oestrogen is a female sex hormone that stimulates the immune system against viral infection. On the contrary, the testosterone secreted by the men’s gonads suppresses the immune system against COVID-19 infection. Female sex hormones may reduce the ACE2 mRNA expression, and thus men are more prone to any viral attack than females, which is predominant in the case of SARS-CoV-2 [30,31].

2. Long-Term Health Complications

Table 1 shows the results of different analyses from around the world about the incident and how conditions after COVID-19 still exist. A few other data points are likewise discussed in this section.
Table 1. Case study findings on the occurrence of post-COVID-19 syndrome (1–6 months of post-COVID follow-up).

2.1. Cardiovascular Complications

Patients who became sick with SARS-CoV-2 had heart problems after they got better, such as low blood pressure, a slow heart rate, and atrial fibrillation [45], and about 20% of COVID-19 patients who becamebetter reported chest pain up to 60 days later [46]. The myocardial tissues, including the alveoli and the lungs, consist of an ACE2 receptor where the virus binds to the receptor and decreases expression of ACE2, which is a cardio-protective transmembrane protein widespread in many tissues such as the kidney, lungs, heart, and intestine. Moreover, following SARS-CoV-2 infection, many people are diagnosed with cardiac arrhythmias with an increased troponin level [47,48,49,50,51].
Several reports highlighted that pneumonia is a predominant symptom seen in SARS-CoV-2-affected patients, some of whom may require hospitalization. These patients have a high chance of having cardiovascular complications after recovery. Corticosteroids are infrequently suggested for COVID-19 patients with lung damage. However, in severe cases, corticosteroids were applied, which in turn affected the cardiovascular tissues [52]. Reported cases also highlighted those patients with no history of cardiac problems who developed malignant arrhythmias and acute respiratory failure, leading to death. Moreover, the increased troponin level also resulted in the cardiac arrest of the patients after recovery. Based on the cases reported in previous outbreaks like SARS-CoV and MERS-CoV, 40% of recovered subjects have had persistent cardiovascular problems for a long time [53]. The same scenario is expected in the case of COVID-19.
Those who survived COVID-19 have a higher cardiometabolic demand, just like those who survived SARS. This can happen when the heart’s reserve capacity is low, when corticosteroids are used, or when the renin–angiotensin–aldosterone system doesn’t work well [54]. Weerahandi and co-workers reported a study conducted in New York that indicated 74% out of 152 subjects faced difficulty breathing [11]. Another population study with 200 patients in the UK also indicated the prevalence of cardiorespiratory trouble encountered by 40% of the subjects after 30 days of negativization [55].

2.2. Respiratory Complications

SARS-CoV-2 mostly affects the lungs. The severe attack on the lungs develops critical manifestations such as respiratory failures and pneumonia, constituting a prime reason for COVID-19-associated mortality [56]. Inflammation and pulmonary fibrosis are the two main effects of a viral lung infection. This inflammation affects the tiny air sacs called alveoli, which help in the diffusion of respiratory gases. Post-mortem analysis of several COVID patients has shown an extreme level of lung congestion, and the parenchymal cells present in the lungs are highly inflamed and appear to be bluish-red [57]. The histopathological reports of lung tissue samples indicated the congestion of the small and large airways, including the pleural tissue and capillaries. These examinations also gave evidence of acute bronchopneumonia, emphysema, asthma, etc. [58]. These severe complications have a high chance of being prevalent in the long run after the patient’s recovery.
Most survivors of COVID-19 have pulmonary symptoms such as dyspnea, which have been reported in 42% to 66% of cases at 60 to 100 days of follow-up [59]. When standard radiological imaging has been used to find respiratory problems, they have been described as having segmentation of the lungs and opacities that look like glass. The lung segmentation pattern shows how viral loads can damage the lungs and make them less able to hold air. In some patients (about 5%), the CTs (computed tomography scan) findings indicated lymphadenopathies, pleural effusions, and cavitations. These findings are more prominent in positive RT-PCR patients with respiratory troubles than in those with non-respiratory symptoms [60,61]. Patients with COVID-19 use high doses of steroids to treat their lung inflammation. According to research by scientists, there is evidence that such steroid application for other coronavirus infections has also contributed to the development of lung fibrosis, a chronic health condition [62,63].
The aging process in people also results in some cellular dysfunctions; as a result, the immune system in such people fails to control the viral encounter, leading to some lung-related problems, including lung fibrosis [64]. However, the post-COVID complications due to SARS-CoV-2 have not yet been evident on a large scale, but owing to the evidence from other cases of coronavirus infections, similar complications may likely appear. Additionally, pulmonary vascular microthrombosis as well as macrothrombosis have been perceived in almost 20% to 30% of COVID-19 patients with endothelial injury [65,66,67].
When the SARS-CoV-2 virus first gets into a person’s body, it comes into contact with the mucous membranes in the eyes, mouth, and nose. First, the virus moves into a healthy cell and starts making copies of itself. This creates new virus particles that spread to all healthy cells nearby. Recent reports say that this new coronavirus can infect the whole respiratory system of a person [68]. Once it goes through our airways and gets to our alveoli, the lining could becomered and irritated. This novel coronavirus infection is new, and doctors and scientists are constantly learning more and more every day about the pathophysiology of this disease, which has similar effects on the human body to other coronavirus-related diseases, such as SARS and MERS. A retrospective study in Wuhan, China, demonstrated that the CTs showed that about 98% of people had impaired lung functions [69].
Alveoli are tiny air sacs in the lungs responsible for gas exchange between the air and the blood. There are three parts to the alveolar wall: (a) the alveolar epithelium with the basement membrane; (b) the capillary endothelium with the basement membrane; and (c) an interstitium with the fused basement membranes and fibroblasts, elastic fibers, macrophages, and collagen fibrils. The SARS-CoV-2 virus is responsible for the respiratory illness COVID-19, which primarily affects the alveoli and respiratory system. The role of alveolar injuries in the disease progression of COVID-19 is crucial. The alveolar injuries and the subsequent inflammation cause a reduction in the oxygen exchange capacity of the lungs, leading to hypoxemia (low blood oxygen levels). Hypoxemia can further exacerbate the inflammation and damage to the alveoli, creating a vicious cycle of lung injury. Alveolar injuries also play a role in the development of blood clots in COVID-19 patients, which can lead to complications such as pulmonary embolism and stroke. Therefore, alveolar injuries are a crucial component of the disease progression of COVID-19, leading to severe respiratory complications such as ARDS (acute respiratory distress syndrome) and hypoxemia, as well as potentially life-threatening blood clotting disorders. Effective management of COVID-19 requires a comprehensive approach that addresses both the viral infection and the resulting lung injury [70].

2.3. Gastrointestinal Complications

The fact that the ACE2 receptor is found in the GI (gastrointestinal) tract makes it easy for SARS-CoV-2 to take over [71]. Patients who becamebetter had higher levels of SGPT (serum glutamic–pyruvic transaminase), SGOT (serum glutamic–oxaloacetic transaminase), bilirubin, and other enzymes that the liver needs to work well. The elevated levels had given clear evidence of the problem in the liver [72]. Other than the liver, the other gastrointestinal complications include dysbiosis, visceral hypersensitivity, and enhanced intestinal permeability, which leads to inadequate absorption of bile acid together with problems related to some metabolic pathways. Moreover, evidence suggests that viral attacks may lead to functional gastrointestinal disorders or disorders in the gut–brain interaction, although this symptom does not persist for a very long time [73]. In about 20% of patients, it is observed that the virus was found in the stool even after getting negative results. Authorities have also decided to discharge a hospitalized patient only after getting negative results from the RT-PCR of stool [74]. Interestingly, a few patients developed GI symptoms rather than any respiratory complications [75,76].
Most drugs used to treat SARS-CoV-2 infections have major side effects on the GI tract, liver, stomach, and pancreas, which change the environment in the gut [77]. These complications of the GI tract (hepatobiliary, bowel ischemia, hypomotility, and others) are more likely to happen during COVID-19 and after recovery in people who had GI symptoms at the start of their viral symptoms [78]. According to the reports published by Arnold et al., 2020, and Moreno-Pérez et al., 2021, case studies in the United Kingdom (110 people) and Spain (277 people) reported that 0.9% and 10.5% faced diarrhea problems after 3 months of negativization [35,36].

2.4. Neurological Complications

Spike protein–ACE2 receptor interaction leads to the dysfunction of cell signaling processing, which in turn affects the functioning of the olfactory and gustatory organs. This may lead to adverse neurological complications in the long run due to the entry of the virus into the brain via the nasal cavity [79,80]. Stroke, encephalitis, and other cerebrovascular diseases are among the leading causes of human suffering [81]. Post-Covid neurological problems thatare seen in a large number of patients include anosmia, headaches, and stroke in some cases. The pathway of the virus toward the brain leads to olfactory dysfunction (namely, anosmia) [82].
Normal neurological effects of this impairment fall into three groups: problems with the central nervous system, problems with the peripheral nervous system, and injuries to the bones and muscles. These manifestations together lead to headaches, dizziness, anosmia, vision problems, etc. [83]. The virus is also found in the cerebrospinal fluid (CSF) of many people. Many pieces of evidence suggest that the positive patients only had headache and anosmia as their only symptoms. According to the last report, 96 patients with stroke have been reported following an increased level of ferritin, D-dimer, and C-reactive protein. In addition, another exclusive case study was conducted on a 56-year-old man who tested positive for the virus in March 2020. Later, he was examined for certain neurological complications after 6 months of recovery. He required a routine EEG examination and overcame momentary epileptic seizures [84]. A case was reported on the prevalence of long-term anosmia in a 40-year-old Brazilian lady even after 85 days of recovery [85].

2.5. Psychiatric Complications

The SARS-CoV-2 distresses the brain, which houses several neuronal circuits, just like the other two infectious members of the Coronavirideae family [86,87,88,89,90]. A viral infection in the brain stem lowers the number of ACE2 receptors. This kills neurons and changes how several baroreceptors work [91,92]. In the long run, post-traumatic stress disorder (PTSD) will be a common problem. This is not only due to the viral attack in the brain but also to this severe pandemic and a high mortality rate associated with many complications [93]. Several neuropsychiatric problems, including auditory and visual hallucinations, schizophrenia, PTSD, epilepsy, etc., are reported after COVID-19 recovery [51].
Furthermore, COVID-19 patients passed through an extremely stressful period. Some of them even had very severe complications and needed hospitalization. They even required the support of ventilators. They were isolated for 14 days, kept away from their near and dear ones, their workplace, society, etc. This isolation and detachment have created trauma or anxiety. After getting back to their normal lives, they are unable to overcome this problem; they need to consult psychiatrists [94]. The pandemic forced the government (both state and central) to initiate a complete lockdown over 3 months, culminating in the unemployment of many people in 2020, especially in India. These changes somehow created psychological problems, which are likely to persist. India suffered greatly from the second COVID-19 surge even in 2021, which had a greater impact than it had in the previous year [95,96,97]. A potential study of 91 patients conducted in Santiago, Spain, foundevidence of post-COVID anxiety and depression among 46% of the subjects [98]. A collective study conducted in Hall, UK, with a total of 134 subjects, also showed the prevalence of sleep disturbances (35.1%) and mood disturbances (37.3%) after recovering from SARS-CoV-2 infection [99].

2.6. Dermatological Complications

The urticarial lesions, maculopapular lesions, vesicular lesions, necrosis, and liver lesions that have been reported are caused by the interaction between the spike protein and the ACE2 receptor in the basal cells of the epidermis [100]. Many of the patients even had oral ulcers and blisters. Another very common symptom observed in the case of children was rashes on the skin [101,102]. Adverse dermatological manifestations included varicella-like exanthems, which can persist for 12 days [103]. No cases with severe dermatological manifestations were found to prevail in the long run during previous coronavirus outbreaks, which may not remain the same in the present scenario. The most common dermatological complication observed among 20% of the patient population after recovering from COVID was reported hair loss [9].

2.7. Renal Complications

Acute kidney injury (AKI), electrolyte disturbances, and renal replacement therapy (RRT) are some of the most common renal complications that have been associated with COVID-19 patients [104]. A prominent cause of COVID-19-related death other than proteinuria and haematuria is AKI [105]. Long-term renal complications in patients are also caused by AKI, potentially causing microalbuminuria and chronic kidney diseases; as a result, they require routine dialysis, and about 40% of patients who had AKI needed intensive care [106]. Renal problems will prevail in the long run because the involvement of the kidneys was also prevalent in the cases of SARS and MERS. A prospective study in Oxford, UK, showed that 29% of 58 subjects developed acutepost-COVID renal complications [107].

2.8. Gonadal Complications

The ACE2 receptor is principally present in the Leydig cells and Sertoli cells of males. Spermatogenesis will be dysfunctional in the case of ACE2-positive spermatogonia [108]. Infection of Sertoli cells leads to dysfunctioning of the spermatogenesis cycle because the viral entry destroys the seminiferous epithelium barrier of the cells, which provides a barrier to the spermatogonia from the cytotoxic products of the blood [109]. Destruction of this obstacle, in turn, affects the process of spermatogenesis.
The decrement of the ACE2 receptor due to the viral attack decreases sperm motility because the ACE2-angiotensin-(1–7)-Mas receptor maintains sperm mobility by activating the PI3K/AKT pathway [110,111]. Recent studies have also indicated the alteration of the levels of several androgens and gonadotrophins in male patients. The considerable diminution in the level of LH (luteinizing hormone) indicates that the SARS-CoV-2 virus has less effect on Sertoli cells than Leydig cells [112].

3. Immunological Changes in the Course of Long COVID

Post-COVID-19 symptoms (long COVID) can affect people with a history of SARS-CoV-2 infection regardless of age and gender, and the fact that long COVID may appear in people with mild symptoms is also worrying the authorities even more. COVID-19 recurrence is reported to increase the probability of long COVID symptoms even more [113]. The menace and liability of sequelae due to SARS-CoV-2 reinfection were significantly higher compared to persons who did not get reinfection. This has concerned the authorities even more, as strategies for the prevention of reinfection are of the utmost importance in managing long COVID.
Dr. Janet Diaz, Unit Head, Clinical Management, WHO Health Emergencies Programme, explains that it is still not clear how many days long COVID may remain as cases have been reported to continue even after nine months. Still, we have not been able to fully understand the reason and the mechanism of long COVID. At the same time, common indications of long COVID include dyspnoea, lethargy, and/or cognitive dysfunction. However, more than 200 other symptoms have also been reported for long COVID [114], the majority of which are associated with the malfunctioning of the visceral organs like the heart, lungs, liver, pancreas, and spleen. The mechanism for long COVID is still unclear, and different studies are still going on that emphasize different plausible mechanisms that have been discussed below.
The broad mechanisms proposed for explaining the activation of autoimmune disease are bystander activation, molecular mimicry, and epitope spreading.

3.1. Bystander Activation and Long COVID

Bystander activation is linked to T-cell and/or B-cell activation that does not involve their receptors. When antigens interact with their corresponding receptors, they usually cause the receptors to become active. A series of activities that result in the production of cytokines, cell differentiation, cell growth, and/or cell death happens next [115]. Unlike what was thought before, not all self-reactive lymphocytes go through apoptosis. Some naive lymphocytes may be able to get around the central tolerance [116,117]. Bystander activation is related to the activation of autoimmune diseases. Viral infection near the sites of these bystander cells or the migration of these bystander cells towards the inflammation sites may trigger unspecific activation of these lymphocytes without the involvement of B-cell receptors and/or T-cell receptors [115]. Gregorova et al., 2020, have proposed bystander T-lymphocyte activation in post-acute COVID-19 complications. They saw an abundance of CD8+ TEMRA (terminally differentiated effector memory cells re-expressing CD45RA) cells among the spike-1-specific CD8+ cell population. CD8+ TEMRA cells may be activated in the presence of cytokines only, without involving TCR (T-cell receptor) [118,119]. T cells mediate the connection between the thyroid gland and autoimmunity, and long COVID-19 cases have reported inappropriate thyroid gland functioning with autoimmune pathophysiology [120]. Autoimmune consequences of long COVID also involve B cells, as evidenced by the presence of autoantibodies against phospholipids, cyclic citrullinated peptides, connective tissue, neutrophils, and interferons [121,122,123,124].

3.2. Molecular Mimicry and Epitope Spreading in Long COVID

If the pathogen and the host share antigens, the host may have an autoimmune response. It is called “molecular mimicry” when an antigen from an outside pathogen causes the body to attack itself. A bioinformatics study predicted the presence of such shared antigens in SARS-CoV-2 spike glycoprotein with that of the adrenal cortex, pituitary, thyroid surface proteins, and beta cells of the islets of Langerhans. This is most likely what causes neuroendocrine dysfunction in long COVID. However, more in vivo studies need to be done to further verify this [125]. Another plausible mechanism underlying the autoimmune-pathological condition of long COVID may be due to epitope spreading [126]. Our immune system not only targets a particular antigen of a pathogen, but temporal diversification of the immune system to target multiple epitopes of a pathogen may also take place. In a study, it was seen that people who could not suppress SARS-CoV-2 early might have a higher virus load for a prolonged period, which may lead to antibody evolution and epitope spreading [127].

References

  1. Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? The Lancet 2020; 395: 1225–8.
  2. Holshue ML, DeBolt C, Lindquist S et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med 2020; 382: 929–36.
  3. Bernard Stoecklin S, Rolland P, Silue Y et al. First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020. Eurosurveillance 2020; 25: 2000094.
  4. Gul, S., Ozcan, O., Asar, S., Okyar, A., Barıs, I., &Kavakli, I. H. (2020). In silico identification of widely used and well-tolerated drugs as potential SARS-CoV-2 3C-like protease and viral RNA-dependent RNA polymerase inhibitors for direct use in clinical trials. Journal of Biomolecular Structure and Dynamics, 1-20.
  5. Zhu, Zhixing, XihuaLian, Xiaoshan Su, Weijing Wu, Giuseppe A. Marraro, and Yiming Zeng. (2020) From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses." Respiratory research 21 (1): 1-14.
  6. Ludwig, S., & Zarbock, A. C. SARS-CoV-2. Anesth Analg In press doi, 10.
  7. Zhou, Zhonghua, Ziyi Yang, JunxianOu, Hong Zhang, Qiwei Zhang, Ming Dong, and Gong Zhang. (2021) Temperature dependence of the SARS-CoV-2 affinity to human ACE2 determines COVID-19 progression and clinical outcome. Computational and structural biotechnology journal 19:161-167.
  8. Guan, W. J., Liang, W. H., Zhao, Y., Liang, H. R., Chen, Z. S., Li, Y. M., ... & He, J. X. (2020). Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. European Respiratory Journal, 55(5).
  9. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22.
  10. Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, Scarlata S, Agrò FE. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020 Aug;288 (2):192-206. doi: 10.1111/joim.13091. Epub 2020 May 13.
  11. Zhang, J., Xie, B., & Hashimoto, K. (2020). Current status of potential therapeutic candidates for the COVID-19 crisis. Brain, behavior, and immunity.
  12. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020.
  13. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181: 271–280.e8, 2020. doi:10.1016/j.cell.2020.02.052.
  14. Van den Brand J, Haagmans BL, Leijten L, van Riel D, Martina BE, Osterhaus A, Kuiken T. Pathology of experimental SARS coronavirus infection in cats and ferrets. Vet Pathol. 2008;45(4):551–62.
  15. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, Liu R, He X, Shuai L, Sun Z. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science. 2020;368(6494):1016–20.
  16. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 2020.
  17. Say, Daniela, Nigel Crawford, Sarah McNab, Danielle Wurzel, Andrew Steer, and ShidanTosif. "Post-acute COVID-19 outcomes in children with mild and asymptomatic disease." The Lancet Child & Adolescent Health (2021).DOI:https://doi.org/10.1016/S2352-4642(21)00124-3.
  18. Feldstein, L. R., Tenforde, M. W., Friedman, K. G., Newhams, M., Rose, E. B., Dapul, H., ... & Overcoming COVID-19 Investigators. (2021). Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. Jama, 325(11), 1074-1087.
  19. Buonsenso, D., Munblit, D., De Rose, C., Sinatti, D., Ricchiuto, A., Carfi, A., & Valentini, P. (2021). Preliminary evidence on long COVID in children. Acta Paediatrica (Oslo, Norway: 1992), 110(7), 2208.
  20. Ludvigsson, J. F. (2021). Case report and systematic review suggest that children may experience similar long‐term effects to adults after clinical COVID‐19. Acta Paediatrica, 110(3), 914-921.
  21. Hu, Z., Song, C., Xu, C., Jin, G., Chen, Y., Xu, X., ... & Shen, H. (2020). Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Science China Life Sciences, 63, 706-711.
  22. Shah, P., Owens, J., Franklin, J., Mehta, A., Heymann, W., Sewell, W., ... & Doshi, R. (2020). Demographics, comorbidities and outcomes in hospitalized Covid-19 patients in rural southwest Georgia. Annals of medicine, 52(7), 354-360.
  23. Chan, J. F. W., Yuan, S., Kok, K. H., To, K. K. W., Chu, H., Yang, J., ... & Yuen, K. Y. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The lancet, 395(10223), 514-523.
  24. Tao, Y., Cheng, P., Chen, W., Wan, P., Chen, Y., Yuan, G., ... & Zhu, C. (2020). High incidence of asymptomatic SARS-CoV-2 infection, Chongqing, China. MedRxiv, 2020-03.
  25. Song, H., Xiao, J., Qiu, J., Yin, J., Yang, H., Shi, R., & Zhang, W. (2020). A considerable proportion of individuals with asymptomatic SARS-CoV-2 infection in Tibetan population. MedRxiv, 2020-03.
  26. Hu, B., Guo, H., Zhou, P., & Shi, Z. L. (2021). Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology, 19(3), 141-154.
  27. Office of the Commissioner. Coronavirus disease 2019 (COVID‐19). U.S. Food and Drug Administration. 2020. https://www.fda.gov/emergency-preparedness-and-response/counterterrorism-and-emerging-threats/coronavirus-disease-2019-covid-19.
  28. Roychoudhury, S., Das, A., Jha, N. K., Kesari, K. K., Roychoudhury, S., Jha, S. K., ... & Slama, P. (2021). Viral pathogenesis of SARS-CoV-2 infection and male reproductive health. Open biology, 11(1), 200347.
  29. Gargaglioni, L. H., Marques, D. A., & Patrone, L. G. A. (2019). Sex differences in breathing. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 238, 110543.
  30. Klein SL, Flanagan KL. Sex differences in immune responses(2016). Nat Rev Immunol 16: 626–638.
  31. Selek, A., Güçlü, M., & Bolu, Ş. E. (2021). COVID-19 pandemic: what about the gonads?. Hormones, 20(2), 259-268.
  32. Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent symptoms in patients after acute COVID-19. Jama, 324(6), 603-605.
  33. Halpin, Stephen J., Claire McIvor, Gemma Whyatt, Anastasia Adams, Olivia Harvey, Lyndsay McLean, Christopher Walshaw et al. (2021) "Postdischarge symptoms and rehabilitation needs in survivors of COVID‐19 infection: A cross‐sectional evaluation." Journal of medical virology 93, no. 2: 1013-1022.
  34. Carvalho-Schneider, C., Laurent, E., Lemaignen, A., Beaufils, E., Bourbao-Tournois, C., Laribi, S., ... & Bernard, L. (2021). Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clinical Microbiology and Infection, 27(2), 258-263.
  35. Arnold, D. T. et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax https://doi.org/10.1136/thoraxjnl-2020-216086 (2020).
  36. Moreno-Pérez, O., Merino, E., Leon-Ramirez, J. M., Andres, M., Ramos, J. M., Arenas-Jiménez, J., ... & Amo, A. (2021). González-delaAleja P., Boix V., Gil J.; COVID19-ALC research group. Post-acute COVID-19 syndrome. Incidence and risk factors: a Mediterranean cohort study. The Journal of Infection, 82(3), 378.
  37. Mahmud R, Rahman MM, Rassel MA, Monayem FB, Sayeed SKJB, Islam MS, et al. (2021) Post-COVID-19 syndrome among symptomatic COVID-19 patients: A prospective cohort study in a tertiary care center of Bangladesh. PLoS ONE 16(4): e0249644.
  38. Garrigues, E., Janvier, P., Kherabi, Y., Le Bot, A., Hamon, A., Gouze, H., and Nguyen, Y. (2020). Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. Journal of Infection, 81(6), e4-e6.
  39. Huang, C., Huang, L., Wang, Y., Li, X., Ren, L., Gu, X., ... & Cao, B. (2021). 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet, 397(10270), 220-232.
  40. Lueger-Schuster, B., Zrnić Novaković, I., & Lotzin, A. (2022). Two Years of COVID-19 in Austria—Exploratory Longitudinal Study of Mental Health Outcomes and Coping Behaviors in the General Population. International Journal of Environmental Research and Public Health, 19(13), 8223.
  41. Tosato, M., Carfì, A., Martis, I., Pais, C., Ciciarello, F., Rota, E., and Team, P. A. C. (2021). Prevalence and predictors of persistence of COVID-19 symptoms in older adults: a single-center study. Journal of the American Medical Directors Association, 22(9), 1840-1844.
  42. Ozturk, S., Turgutalp, K., Arici, M., Gorgulu, N., Tonbul, H. Z., Eren, N., and Ates, K. (2022). The Longitudinal Evolution of Post–COVID-19 Outcomes Among Hemodialysis Patients in Turkey. Kidney international reports.
  43. Daher, A., Balfanz, P., Cornelissen, C., Müller, A., Bergs, I., Marx, N., and Müller, T. (2020). Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae. Respiratory medicine, 174, 106197.
  44. Kamal, M., Abo Omirah, M., Hussein, A., and Saeed, H. (2021). Assessment and characterisation of post‐COVID‐19 manifestations. International journal of clinical practice, 75(3), e13746.
  45. Yu, C. M., Wong, R. S., Wu, E. B., Kong, S. L., Wong, J., Yip, G. W., ... & Sung, J. J. (2006). Cardiovascular complications of severe acute respiratory syndrome. Postgraduate medical journal, 82(964), 140-144.
  46. Weerahandi, H., Hochman, K. A., Simon, E., Blaum, C., Chodosh, J., Duan, E., ... & Horwitz, L. I. (2021). Post-discharge health status and symptoms in patients with severe COVID-19. Journal of general internal medicine, 36, 738-745.
  47. Akhmerov, A., & Marbán, E. (2020). COVID-19 and the heart. Circulation research, 126(10), 1443-1455.
  48. Zhang, J. Y., & Xie, X. (2020). COVID-19 and the cardiovascular system. Nat Rev Cardiol, 17, 259-60.
  49. Bhatraju, P. K., Ghassemieh, B. J., Nichols, M., Kim, R., Jerome, K. R., Nalla, A. K., ... & Mikacenic, C. (2020). Covid-19 in critically ill patients in the Seattle region—case series. New England Journal of Medicine, 382(21), 2012-2022.
  50. Shi, S., Qin, M., Shen, B., Cai, Y., Liu, T., Yang, F., ... & Huang, C. (2020). Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA cardiology, 5(7), 802-810.
  51. Siripanthong, B., Nazarian, S., Muser, D., Deo, R., Santangeli, P., Khanji, M. Y., ... & Chahal, C. A. A. (2020). Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart rhythm, 17(9), 1463-1471.
  52. Li, S., Wang, Y., Xue, J., Zhao, N., & Zhu, T. (2020). The impact of COVID-19 epidemic declaration on psychological consequences: a study on active Weibo users. International journal of environmental research and public health, 17(6), 2032.
  53. Wu, Q., Zhou, L., Sun, X., Yan, Z., Hu, C., Wu, J., ... & Chen, H. (2017). Altered lipid metabolism in recovered SARS patients twelve years after infection. Scientific reports, 7(1), 1-12.
  54. Liu, P. P., Blet, A., Smyth, D., & Li, H. (2020). The science underlying COVID-19: implications for the cardiovascular system. Circulation, 142(1), 68-78.
  55. Hall, J., Myall, K., Lam, J. L., Mason, T., Mukherjee, B., West, A., & Dewar, A. (2021). Identifying patients at risk of post-discharge complications related to COVID-19 infection. Thorax, 76(4), 408-411.
  56. Richardson, S., Hirsch, J. S., Narasimhan, M., Crawford, J. M., McGinn, T., Davidson, K. W., ... & Northwell COVID-19 Research Consortium. (2020). Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. Jama, 323(20), 2052-2059.
  57. Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N, Frank S, Turek D, Willi N, Pargger H, Bassetti S, Leuppi JD, Cathomas G, Tolnay M, Mertz KD, Tzankov A. (2020) Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology, 77(2):198-209.
  58. Calabrese, F., Pezzuto, F., Fortarezza, F., Hofman, P., Kern, I., Panizo, A., … Lunardi, F. (2020). Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. VirchowsArchiv. doi:10.1007/s00428-020-02886-6.
  59. Chopra, V., Flanders, S. A., O’Malley, M., Malani, A. N., & Prescott, H. C. (2021). Sixty-day outcomes among patients hospitalized with COVID-19. Annals of internal medicine, 174(4), 576-578.
  60. Kanne, J. P., Little, B. P., Chung, J. H., Elicker, B. M., & Ketai, L. H. (2020). Essentials for radiologists on COVID-19: an update—radiology scientific expert panel. Radiology, 296(2), E113-E114.
  61. Fangyao, L. W., Leilei, P., Xin, Q., & Chao, L. Potential false-positive rate among the’asymptomatic infected individuals’ in close contact with COVID-19 patients Zhuang Guihua. Shen Mingwang, Zeng Lingxia, Mi Baibing, Chen.
  62. Ngai, J. C., Ko, F. W., Ng, S. S., TO, K. W., Tong, M., & Hui, D. S. (2010). The long‐term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology, 15(3), 543-550.
  63. Zhang, P., Li, J., Liu, H., Han, N., Ju, J., Kou, Y., ... & Jiang, B. (2020). Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone research, 8(1), 8.
  64. Lawson, W. E., Crossno, P. F., Polosukhin, V. V., Roldan, J., Cheng, D. S., Lane, K. B., ... & Blackwell, T. S. (2008). Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. American Journal of Physiology-Lung Cellular and Molecular Physiology, 294(6), L1119-L1126.
  65. Cui, Songping, Shuo Chen, Xiunan Li, Shi Liu, and Feng Wang. (2020) Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis, 18 (6): 1421-1424.
  66. Poissy, Julien, Julien Goutay, Morgan Caplan, Erika Parmentier, ThibaultDuburcq, Fanny Lassalle, Emmanuelle Jeanpierre, Antoine Rauch, Julien Labreuche, and Sophie Susen. (2020) Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation 142 (2): 184-186.
  67. Léonard-Lorant, I., Delabranche, X., Séverac, F., Helms, J., Pauzet, C., Collange, O., ... & Ohana, M. (2020). Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to d-dimer levels. Radiology, 296(3), E189-E191.
  68. Paules, C. I., Marston, H. D., & Fauci, A. S. (2020). Coronavirus infections—More than just the common cold. Jama, 323(8), 707-708.
  69. Ding X, Xu J, Zhou J, Long Q. (2020) Chest CT findings of COVID-19 pneumonia by duration of symptoms. Eur J Radiol. 127:109009. doi: 10.1016/j.ejrad.2020.109009.
  70. Li, X., Ma, X. Acute respiratory failure in COVID-19: is it “typical” ARDS?.Crit Care 24, 198 (2020). https://doi.org/10.1186/s13054-020-02911-9
  71. Cha MH, Regueiro M, Sandhu DS. (2020) Gastrointestinal and hepatic manifestations of COVID-19: a comprehensive review. World J Gastroenterol, 26 (19):2323–2332.
  72. Mao, R., Qiu, Y., He, J. S., Tan, J. Y., Li, X. H., Liang, J., ... & Chen, M. H. (2020). Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. The lancet Gastroenterology & hepatology, 5(7), 667-678.
  73. Barbara, G., Grover, M., Bercik, P., Corsetti, M., Ghoshal, U. C., Ohman, L., & Rajilić-Stojanović, M. (2019). Rome foundation working team report on post-infection irritable bowel syndrome. Gastroenterology, 156(1), 46-58.
  74. Pan, L., Mu, M. I., Yang, P., Sun, Y., Wang, R., Yan, J., ... & Tu, L. (2020). Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. The American journal of gastroenterology, 115.
  75. Tran J, Glavis-Bloom J, Bryan T, Harding KT, Chahine C, Houshyar R. (2020) COVID-19 patient presenting with initial gastrointestinal symptoms. ESR.
  76. An P, Chen H, Jiang X, Su J, Xiao Y, Ding Y, Ren H, Ji M, Chen Y, Chen W, Lv X, Shen L, Chen M, Li J, Yin A, Kang J, Liu S, Tan W, Wu L, Dong W, Cao J, Zhou Z, Tan S, Chen G, Zhou J, Yang Y, Yu H. (2020) Clinical Features of 2019 Novel Coronavirus Pneumonia Presented Gastrointestinal Symptoms But Without Fever Onset.
  77. Khan, I., Ullah, N., Zha, L., Bai, Y., Khan, A., Zhao, T., ... & Zhang, C. (2019). Alteration of gut microbiota in inflammatory bowel disease (IBD): cause or consequence? IBD treatment targeting the gut microbiome. Pathogens, 8(3), 126..
  78. Kaafarani, H. M., El Moheb, M., Hwabejire, J. O., Naar, L., Christensen, M. A., Breen, K., ... & Velmahos, G. C. (2020). Gastrointestinal complications in critically ill patients with COVID-19. Annals of surgery, 272(2), e61.
  79. Paderno, A., Schreiber, A., Grammatica, A., Raffetti, E., Tomasoni, M., Gualtieri, T., ... & Mattavelli, D. (2020, August). Smell and taste alterations in COVID‐19: a cross‐sectional analysis of different cohorts. In International forum of allergy & rhinology (Vol. 10, No. 8, pp. 955-962).
  80. Whitcroft KL, Hummel T. (2020) Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 323(24):2512–2514.
  81. Chen, Q., Cao, C., Gong, L., & Zhang, Y. (2019). Health related quality of life in stroke patients and risk factors associated with patients for return to work. Medicine, 98(16).
  82. Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. (2020) Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA Neurol. 77(8):1018-1027.
  83. Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., ... & Hu, B. (2020). Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA neurology, 77(6), 683-690.
  84. Nuzzo D, Cambula G, Bacile I, Rizzo M, Galia M, Mangiapane P, Picone P, Giacomazza D, Scalisi L. (2021) Long-Term Brain Disorders in Post Covid-19 Neurological Syndrome (PCNS) Patient. Brain Sci. 11(4):454.
  85. Sampaio Rocha-Filho PA, Voss L. (2020) Persistent headache and persistent anosmia associated with COVID-19. Headache. 60:1797–9.
  86. Benarroch, E. E. (2007) Brainstem respiratory chemosensitivity: new insights and clinical implications. Neurology, 68, 2140–2143.
  87. Ikeda, K., Kawakami, K., Onimaru, H., Okada, Y., Yokota, S., Koshiya, N., ... & Koizumi, H. (2017). The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology. The journal of physiological sciences, 67(1), 45-62.
  88. Burks, S. M., Rosas-Hernandez, H., Ramirez-Lee, M. A., Cuevas, E., & Talpos, J. C. (2021). Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?. Brain, behavior, and immunity, 95, 7-14.
  89. DosSantos, M. F., Devalle, S., Aran, V., Capra, D., Roque, N. R., Coelho-Aguiar, J. D. M., ... & Moura-Neto, V. (2020). Neuromechanisms of SARS-CoV-2: a review. Frontiers in neuroanatomy, 14, 37.
  90. Pereira, A. (2020). Long-term neurological threats of COVID-19: a call to update the thinking about the outcomes of the coronavirus pandemic. Frontiers in neurology, 11, 308.
  91. Alenina, N., & Bader, M. (2019). ACE2 in brain physiology and pathophysiology: evidence from transgenic animal models. Neurochemical research, 44, 1323-1329.
  92. Diz, D. I., Garcia‐Espinosa, M. A., Gegick, S., Tommasi, E. N., Ferrario, C. M., Ann Tallant, E., ... & Gallagher, P. E. (2008). Injections of angiotensin‐converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats. Experimental Physiology, 93(5), 694-700.
  93. Steardo L Jr, Steardo L, Verkhratsky A. Psychiatric face of COVID-19. (2020) Transl Psychiatry. 30;10(1):261.
  94. Sani, G., Janiri, D., Di Nicola, M., Janiri, L., Ferretti, S., & Chieffo, D. (2020). Mental health during and after the COVID‐19 emergency in Italy.
  95. Ershkov, S. V., &Rachinskaya, A. (2021). A new approximation of mean-time trends for the second wave of COVID-19 pandemic evolving in key six countries. Nonlinear Dynamics, 1-20.
  96. Ranjan, R., Sharma, A., & Verma, M. K. (2021). Characterization of the Second Wave of COVID-19 in India. medRxiv.
  97. Sharma, A., Sapkal, S., & Verma, M. K. (2021). Universal epidemic curve for COVID-19 and its usage for forecasting. Transactions of the Indian National Academy of Engineering, 1-9.
  98. Taboada, M., Moreno, E., Cariñena, A., Rey, T., Pita-Romero, R., Leal, S., ... & Seoane-Pillado, T. (2021). Quality of life, functional status, and persistent symptoms after intensive care of COVID-19 patients. British journal of anaesthesia, 126(3), e110-e113.
  99. Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. (2021) Post-COVID-19 symptom burden: what is long-COVID and how should we manage it? Lung. 11:1–7.
  100. Novak, N., Peng, W., Naegeli, M. C., Galvan, C., Kolm‐Djamei, I., Brüggen, C., ... & Catala, A. (2021). SARS‐CoV‐2, COVID‐19, skin and immunology–What do we know so far?. Allergy, 76(3), 698-713.
  101. Galván Casas C, Català A, Carretero Hernández G, et al. (2020) Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 183(1):71–77.
  102. Sinadinos A, Shelswell J. (2021) Oral ulceration and blistering in patients with COVID-19. Evid Based Dent. (2):49–49.
  103. Marzano, A. V., Genovese, G., Fabbrocini, G., Pigatto, P., Monfrecola, G., Piraccini, B. M., ... & Calzavara-Pinton, P. (2020). Varicella-like exanthem as a specific COVID-19–associated skin manifestation: Multicenter case series of 22 patients. Journal of the American Academy of Dermatology, 83(1), 280-285.
  104. Nalbandian, A., Sehgal, K., Gupta, A., Madhavan, M. V., McGroder, C., Stevens, J. S., ... & Wan, E. Y. (2021). Post-acute COVID-19 syndrome. Nature medicine, 27(4), 601-615.
  105. Kunutsor, S. K., & Laukkanen, J. A. (2020). Renal complications in COVID-19: a systematic review and meta-analysis. Annals of medicine, 52(7), 345-353.
  106. Hirsch, J. S., Ng, J. H., Ross, D. W., Sharma, P., Shah, H. H., Barnett, R. L., ... & Northwell COVID-19 Research Consortium. (2020). Acute kidney injury in patients hospitalized with COVID-19. Kidney international, 98(1), 209-218.
  107. Ronco, C., Reis, T., & Husain-Syed, F. (2020). Management of acute kidney injury in patients with COVID-19. The Lancet Respiratory Medicine, 8(7), 738-742.
  108. Raman, B., Cassar, M. P., Tunnicliffe, E. M., Filippini, N., Griffanti, L., Alfaro-Almagro, F., ... & Neubauer, S. (2021). Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine, 31, 100683.
  109. Fan, C., Li, K., Ding, Y., Lu, W. L., & Wang, J. (2020). ACE2 expression in kidney and testis may cause kidney and testis damage after 2019‐nCoV infection. medRxiv.
  110. Archana, S. S., Selvaraju, S., Binsila, B. K., Arangasamy, A., & Krawetz, S. A. (2019). Immune regulatory molecules as modifiers of semen and fertility: A review. Molecular Reproduction and Development, 86(11), 1485–1504.
  111. Valdivia, A., Cortés, L., Beitia, M., Totorikaguena, L., Agirregoitia, N., Corcostegui, B., Casis, L., Matorras, R., Irazusta, J., & Agirregoitia, E. (2020). Role of Angiotensin‐(1–7) via MAS receptor in human sperm motility and acrosome reaction. Reproduction, 159(3), 241–249.
  112. Tsuji, A.,Murakami, M., & Matsuda, S.(2020). COVID‐19, an infertility risk? Clinical Obstetrics, Gynecology and Reproductive Medicine, 6.
  113. Ma, L., Xie, W., Li, D., Shi, L., Mao, Y., Xiong, Y., Zhang, M. (2020). Effect of SARS‐CoV‐2 infection upon male gonadal function: A single center‐based study. medRxiv.
  114. Bowe, B., Xie, Y., & Al-Aly, Z. (2022). Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nature medicine, 1-8.
  115. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science-in-5/episode-47---post-covid-19-condition?gclid=Cj0KCQiA5NSdBhDfARIsALzs2ECs3QKiVjY7lyowKJYn6X6DXpPNPYE7XuoZHx_KtNzvi0k4_A-tj2EaAiD1EALw_wcB.
  116. Pacheco, Y., Acosta-Ampudia, Y., Monsalve, D. M., Chang, C., Gershwin, M. E., & Anaya, J. M. (2019). Bystander activation and autoimmunity. Journal of autoimmunity, 103, 102301.
  117. Xing, Y., & Hogquist, K. A. (2012). T-cell tolerance: central and peripheral. Cold Spring Harbor perspectives in biology, 4(6), a006957.
  118. Hotta-Iwamura, C., Benck, C., Coley, W. D., Liu, Y., Zhao, Y., Quiel, J. A., & Tarbell, K. V. (2018). Low CD25 on autoreactive Tregs impairs tolerance via low dose IL-2 and antigen delivery. Journal of autoimmunity, 90, 39-48.
  119. Gregorova M, Morse D, Brignoli T, Steventon J, Hamilton F, Albur M, Arnold D, Thomas M, Halliday A, Baum H, Rice C, Avison MB, Davidson AD, Santopaolo M, Oliver E, Goenka A, Finn A, Wooldridge L, Amulic B, Boyton RJ, Altmann DM, Butler DK, McMurray C, Stockton J, Nicholls S, Cooper C, Loman N, Cox MJ, Rivino L, Massey RC. (2020) Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia. Elife. 17;9:e63430.
  120. Muller, I., Cannavaro, D., Dazzi, D., Covelli, D., Mantovani, G., Muscatello, A., ... & Salvi, M. (2020). SARS-CoV-2-related atypical thyroiditis. The lancet Diabetes & endocrinology, 8(9), 739-741.
  121. Lui, D. T. W., Lee, C. H., Chow, W. S., Lee, A. C. H., Tam, A. R., Fong, C. H. Y., ... & Lam, K. S. L. (2021). Thyroid dysfunction in relation to immune profile, disease status, and outcome in 191 patients with COVID-19. The Journal of Clinical Endocrinology & Metabolism, 106(2), e926-e935.
  122. Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H. H., Zhang, Y., ... & Casanova, J. L. (2020). Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, 370(6515), eabd4585.
  123. Vlachoyiannopoulos, P. G., Magira, E., Alexopoulos, H., Jahaj, E., Theophilopoulou, K., Kotanidou, A., & Tzioufas, A. G. (2020). Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Annals of the Rheumatic Diseases, 79(12), 1661-1663.
  124. Zhou, Y., Han, T., Chen, J., Hou, C., Hua, L., He, S., ... & Jia, E. (2020). Clinical and autoimmune characteristics of severe and critical cases of COVID‐19. Clinical and translational science, 13(6), 1077-1086.
  125. Gao, Z. W., Zhang, H. Z., Liu, C., & Dong, K. E. (2021). Autoantibodies in COVID-19: frequency and function. Autoimmunity Reviews, 20(3), 102754.
  126. Churilov, L. P., Normatov, M. G., & Utekhin, V. J. (2022). Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity?. Pathophysiology : the official journal of the International Society for Pathophysiology, 29(3), 486–494. https://doi.org/10.3390/pathophysiology29030039.
  127. Powell, A. M., & Black, M. M. (2001). Epitope spreading: protection from pathogens, but propagation of autoimmunity?. Clinical and experimental dermatology, 26(5), 427–433.
  128. Shrock, E., Fujimura, E., Kula, T., Timms, R. T., Lee, I. H., Leng, Y., Robinson, M. L., Sie, B. M., Li, M. Z., Chen, Y., Logue, J., Zuiani, A., McCulloch, D., Lelis, F. J. N., Henson, S., Monaco, D. R., Travers, M., Habibi, S., Clarke, W. A., Caturegli, P., … Elledge, S. J. (2020). Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science (New York, N.Y.), 370(6520), eabd4250.
  129. Hughes, J. P., Rees, S., Kalindjian, S. B., & Philpott, K. L. (2011). Principles of early drug discovery. British journal of pharmacology, 162(6), 1239-1249.
  130. Chakraborty, C., Bhattacharya, M., Mallick, B., Sharma, A. R., Lee, S. S., & Agoramoorthy, G. (2021). SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development. Expert Review of Clinical Pharmacology, 14(2), 225-237.
  131. Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., ... & Overington, J. P. (2017). A comprehensive map of molecular drug targets. Nature reviews Drug discovery, 16(1), 19-34.
  132. Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., ... & Pirmohamed, M. (2019). Drug repurposing: progress, challenges and recommendations. Nature reviews Drug discovery, 18(1), 41-58.
  133. Weinstock, L. B., Brook, J. B., Walters, A. S., Goris, A., Afrin, L. B., & Molderings, G. J. (2021). Mast cell activation symptoms are prevalent in Long-COVID. International Journal of Infectious Diseases, 112, 217-226.
  134. Salmon, D., Slama, D., Linard, F., Dumesges, N., LE BAUT, V., HAKIM, F., ... & MARSHALL, E. (2022). Factors associated with release relief of Long COVID symptoms at 12-Months and their impact on daily life. medRxiv, 2022-11.
  135. Chiappelli, F., & Fotovat-E-mail, L. (2022). Post acute CoViD-19 syndrome (PACS)-Long CoViD. Bioinformation, 18(10), 908-911.
  136. Pinto, M. D., Lambert, N., Downs, C. A., Abrahim, H., Hughes, T. D., Rahmani, A. M., ... & Chakraborty, R. (2022). Antihistamines for postacute sequelae of SARS-CoV-2 infection. The Journal for Nurse Practitioners, 18(3), 335-338.
  137. Crook, H., Raza, S., Nowell, J., Young, M., & Edison, P. (2021). Long covid—mechanisms, risk factors, and management. bmj, 374.
  138. Wu, R., Wang, L., Kuo, H. C. D., Shannar, A., Peter, R., Chou, P. J., ... & Kong, A. N. (2020). An update on current therapeutic drugs treating COVID-19. Current pharmacology reports, 6, 56-70.
  139. Jean, S. S., Lee, P. I., & Hsueh, P. R. (2020). Treatment options for COVID-19: The reality and challenges. Journal of microbiology, immunology and infection, 53(3), 436-443.
  140. Patel, S., Saxena, B., & Mehta, P. (2021). Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19. Heliyon, 7(2), e06158.
  141. Duijvelaar, E., Schippers, J. R., Smeele, P. J., de Raaf, M. A., Vanhove, A. L., Blok, S. G., ... & Aman, J. (2022). Long-term clinical outcomes of COVID-19 patients treated with imatinib. The Lancet Respiratory Medicine, 10(4), e34-e35.
  142. Napoli, C., Benincasa, G., Criscuolo, C., Faenza, M., Liberato, C., &Rusciano, M. (2021). Immune reactivity during COVID-19: Implications for treatment. Immunology letters, 231, 28-34.
  143. Gaylis, N. B., Ritter, A., Kelly, S. A., Pourhassan, N. Z., Tiwary, M., Sacha, J. B., ... & Yang, O. O. (2022). Reduced cell surface levels of CC chemokine receptor 5 and immunosuppression in long Coronavirus disease 2019 syndrome. Clinical Infectious Diseases, 75(7), 1232-1234.
  144. Fernández-de-Las-Peñas, C., Pellicer-Valero, O. J., Navarro-Pardo, E., Palacios-Ceña, D., Florencio, L. L., Guijarro, C., & Martín-Guerrero, J. D. (2022). Symptoms experienced at the acute phase of SARS-CoV-2 infection as risk factor of long-term post-COVID symptoms: the LONG-COVID-EXP-CM multicenter study. International Journal of Infectious Diseases, 116, 241-244.
  145. Bansal, R., Gubbi, S., & Koch, C. A. (2022). COVID-19 and chronic fatigue syndrome: An endocrine perspective. Journal of Clinical & Translational Endocrinology, 27, 100284.
  146. Yong, S. J. (2021). Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infectious diseases, 53(10), 737-754.
  147. Zachrisson, O., Colque-Navarro, P., Gottfries, C. G., Regland, B., & Möllby, R. (2004). Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement. European Journal of Clinical Microbiology and Infectious Diseases, 23, 98-105.
  148. Chee, Y. J., Fan, B. E., Young, B. E., Dalan, R., & Lye, D. C. (2023). Clinical trials on the pharmacological treatment of long COVID: A systematic review. Journal of Medical Virology, 95(1), e28289.
  149. Hufsky, F., Lamkiewicz, K., Almeida, A., Aouacheria, A., Arighi, C., Bateman, A., ... & Marz, M. (2021). Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research. Briefings in bioinformatics, 22(2), 642-663.
  150. Dudley, J. T., Deshpande, T., & Butte, A. J. (2011). Exploiting drug–disease relationships for computational drug repositioning. Briefings in bioinformatics, 12(4), 303-311.
  151. Benson, D. A., Cavanaugh, M., Clark, K., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J., & Sayers, E. W. (2012). GenBank. Nucleic acids research, 41(D1), D36-D42.
  152. Shu, Y., & McCauley, J. (2017). GISAID: Global initiative on sharing all influenza data–from vision to reality. Eurosurveillance, 22(13), 30494., UniProt Consortium. (2007). The universal protein resource (UniProt). Nucleic acids research, 36(suppl_1), D190-D195.
  153. Berman, H. M., Battistuz, T., Bhat, T. N., Bluhm, W. F., Bourne, P. E., Burkhardt, K., ... & Zardecki, C. (2002). The protein data bank. Acta Crystallographica Section D: Biological Crystallography, 58(6), 899-907.
  154. Slonim, D. K., & Yanai, I. (2009). Getting started in gene expression microarray analysis. PLoS computational biology, 5(10), e1000543.
  155. Lonsdale, J., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., ... & Moore, H. F. (2013). The genotype-tissue expression (GTEx) project. Nature genetics, 45(6), 580-585.
  156. Duan Q., Flynn, C., Niepel, M., Hafner, M., Muhlich, J. L., Fernandez, N. F., ... & Ma'ayan, A. (2014). LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures. Nucleic acids research, 42(W1), W449-W460.
  157. Navratil, V., De Chassey, B., Meyniel, L., Delmotte, S., Gautier, C., André, P., ... &Rabourdin-Combe, C. (2009). VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus–host interaction networks. Nucleic acids research, 37(suppl_1), D661-D668.
  158. Guirimand, T., Delmotte, S., & Navratil, V. (2015). VirHostNet 2.0: surfing on the web of virus/host molecular interactions data. Nucleic acids research, 43(D1), D583-D587.
  159. Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., ... & Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583(7816), 459-468.
  160. Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., ... & Mering, C. V. (2019). STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic acids research, 47(D1), D607-D613.
  161. Percha, B., & Altman, R. B. (2018). A global network of biomedical relationships derived from text. Bioinformatics, 34(15), 2614-2624.
  162. Wishart, D. S., Knox, C., Guo, A. C., Cheng, D., Shrivastava, S., Tzur, D., ... & Hassanali, M. (2008). DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic acids research, 36(suppl_1), D901-D906.
  163. Gaulton A., Bellis, L. J., Bento, A. P., Chambers, J., Davies, M., Hersey, A., ... & Overington, J. P. (2012). ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic acids research, 40(D1), D1100-D1107.
  164. Sterling, T., & Irwin, J. J. (2015). ZINC 15–ligand discovery for everyone. Journal of chemical information and modeling, 55(11), 2324-2337.
  165. Williams, R. J., Dobbins, H. D., Tse, T., Chon, S. D., Loose, D., Sarosy, G. A., ... & Zarin, D. A. (2022). Approach for reporting master protocol study designs on ClinicalTrials. gov: qualitative analysis. bmj, 377.
  166. Imming, P., Sinning, C., & Meyer, A. (2006). Drugs, their targets and the nature and number of drug targets. Nature reviews Drug discovery, 5(10), 821-834.
  167. Hajduk, P. J., Huth, J. R., & Fesik, S. W. (2005). Druggability indices for protein targets derived from NMR-based screening data. Journal of medicinal chemistry, 48(7), 2518-2525.
  168. Keller, T. H., Pichota, A., & Yin, Z. (2006). A practical view of ‘druggability’. Current opinion in chemical biology, 10(4), 357-361.
  169. Chen, Y. W., Yiu, C. P. B., & Wong, K. Y. (2020). Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Research, 9.
  170. Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D. S., & Olson, A. J. (2016). Computational protein–ligand docking and virtual drug screening with the AutoDock suite. Nature protocols, 11(5), 905-919.
  171. Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., & Banks, J. L. (2004). Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. Journal of medicinal chemistry, 47(7), 1750-1759.
  172. Gupta, M. K., Vemula, S., Donde, R., Gouda, G., Behera, L., & Vadde, R. (2021). In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. Journal of Biomolecular Structure and Dynamics, 39(7), 2617-2627.
  173. Gentile, F., Agrawal, V., Hsing, M., Ton, A. T., Ban, F., Norinder, U., ... & Cherkasov, A. (2020). Deep docking: a deep learning platform for augmentation of structure based drug discovery. ACS central science, 6(6), 939-949.
  174. Nguyen, D. D., Gao, K., Wang, M., & Wei, G. W. (2020). MathDL: mathematical deep learning for D3R Grand Challenge 4. Journal of computer-aided molecular design, 34, 131-147.
  175. Beck, B. R., Shin, B., Choi, Y., Park, S., & Kang, K. (2020). Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Computational and structural biotechnology journal, 18, 784-790.
  176. Catanzaro, M., Fagiani, F., Racchi, M., Corsini, E., Govoni, S., & Lanni, C. (2020). Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal transduction and targeted therapy, 5(1), 84.
  177. Liao, J., Way, G., & Madahar, V. (2020). Target Virus or Target Ourselves for COVID-19 Drugs Discovery?―Lessons learned from anti-influenza virus therapies. Medicine in Drug Discovery, 5, 100037.
  178. Chen, L., Li, Q., Zheng, D., Jiang, H., Wei, Y., Zou, L., ... & Qiao, J. (2020). Clinical characteristics of pregnant women with Covid-19 in Wuhan, China. New England Journal of Medicine, 382(25), e100.
  179. Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., ... & Golub, T. R. (2006). The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. science, 313(5795), 1929-1935.
  180. Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., ... & Golub, T. R. (2017). A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell, 171(6), 1437-1452.
  181. Jia Z., Song, X., Shi, J., Wang, W., & He, K. (2020). Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19). Pathogens and disease, 78(4), ftaa036.
  182. Law, J. N., Akers, K., Tasnina, N., Della Santina, C. M., Kshirsagar, M., Klein-Seetharaman, J., ... & Murali, T. M. (2020). Identifying human interactors of SARS-CoV-2 proteins and drug targets for COVID-19 using network-based label propagation.
  183. Messina, F., Giombini, E., Agrati, C., Vairo, F., Ascoli Bartoli, T., Al Moghazi, S., ... & Ippolito, G. (2020). COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection. Journal of translational medicine, 18, 1-10.
  184. Fiscon G., & Paci, P. (2021). SAveRUNNER: an R-based tool for drug repurposing. BMC bioinformatics, 22(1), 1-10.
  185. Brin, S., & Page, L. (1998). The anatomy of a large-scale hypertextual web search engine. Computer networks and ISDN systems, 30(1-7), 107-117.
  186. Sadegh, S., Matschinske, J., Blumenthal, D. B., Galindez, G., Kacprowski, T., List, M., ... & Baumbach, J. (2020). Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing. Nature communications, 11(1), 3518.
  187. Cheng, F., Desai, R. J., Handy, D. E., Wang, R., Schneeweiss, S., Barabási, A. L., & Loscalzo, J. (2018). Network-based approach to prediction and population-based validation of in silico drug repurposing. Nature communications, 9(1), 2691.
  188. Zhou Y., Hou, Y., Shen, J., Huang, Y., Martin, W., & Cheng, F. (2020). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell discovery, 6(1), 14.
  189. Morselli Gysi, D., Do Valle, Í., Zitnik, M., Ameli, A., Gan, X., Varol, O., ... & Barabási, A. L. (2021). Network medicine framework for identifying drug-repurposing opportunities for COVID-19. Proceedings of the National Academy of Sciences, 118(19), e2025581118.
  190. Belyaeva, A., Cammarata, L., Radhakrishnan, A., Squires, C., Yang, K. D., Shivashankar, G. V., & Uhler, C. (2021). Causal network models of SARS-CoV-2 expression and aging to identify candidates for drug repurposing. Nature communications, 12(1), 1024.
  191. Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., ... & Rao, Z. (2020). Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 368(6492), 779-782.
  192. Saha, A., Sharma, A. R., Bhattacharya, M., Sharma, G., Lee, S. S., & Chakraborty, C. (2020). Probable molecular mechanism of remdesivir for the treatment of COVID-19: need to know more. Archives of Medical research, 51(6), 585-586.
  193. Grein, J., Ohmagari, N., Shin, D., Diaz, G., Asperges, E., Castagna, A., ... & Flanigan, T. (2020). Compassionate use of remdesivir for patients with severe Covid-19. New England Journal of Medicine, 382(24), 2327-2336.
  194. Antinori, S., Cossu, M. V., Ridolfo, A. L., Rech, R., Bonazzetti, C., Pagani, G., ... & Galli, M. (2020). Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacological research, 158, 104899.
  195. Cai, Q., Yang, M., Liu, D., Chen, J., Shu, D., & Xia, J. (2020). Pengobatan Eksperimental dengan Favipiravir untuk COVID-19: An Open-Label Control Study. Engineering. published online March, 18.
  196. Muralidharan N., Sakthivel, R., Velmurugan, D., & Gromiha, M. M. (2021). Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19. Journal of Biomolecular Structure and Dynamics, 39(7), 2673-2678.
  197. Dalerba, P., Levin, B., & Thompson, J. L. (2020). A trial of Lopinavir–Ritonavir in Covid-19. N Engl J Med, 382(21).
  198. Wen, C. Y., Xie, Z. W., Li, Y. P., Deng, X. L., Chen, X. T., Cao, Y., ... & Li, L. H. (2020). Real-world efficacy and safety of lopinavir/ritonavir and arbidol in treating with COVID-19: an observational cohort study. Zhonghua nei ke za zhi, 59, E012-E012.
  199. Wang, X., & Guan, Y. (2021). COVID‐19 drug repurposing: a review of computational screening methods, clinical trials, and protein interaction assays. Medicinal research reviews, 41(1), 5-28.
  200. Fantini, J., Di Scala, C., Chahinian, H., & Yahi, N. (2020). Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. International journal of antimicrobial agents, 55(5), 105960.
  201. Chong, V. H., Chong, P. L., Metussin, D., Asli, R., Momin, R. N., Mani, B. I., & Abdullah, M. S. (2020). Conduction abnormalities in hydroxychloroquine add on therapy to lopinavir/ritonavir in COVID‐19. Journal of Medical Virology, 92(11), 2322.
  202. Wang Y, Liu Y, Liu L, Wang X, Luo N, Li L. Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China. J Infect Dis. 2020. pii: jiaa119.
  203. Blaising, J., Polyak, S. J., & Pécheur, E. I. (2014). Arbidol as a broad-spectrum antiviral: an update. Antiviral research, 107, 84-94.
  204. Deng, L., Li, C., Zeng, Q., Liu, X., Li, X., Zhang, H., ... & Xia, J. (2020). Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. Journal of Infection, 81(1), e1-e5.
  205. Whitley, R. J. (2007). The role of oseltamivir in the treatment and prevention of influenza in children. Expert Opinion on Drug Metabolism & Toxicology, 3(5), 755-767.
  206. Ye Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the Cytokine Storm in COVID-19. Journal of infection, 80(6), 607-613.
  207. Luo, P., Liu, Y., Qiu, L., Liu, X., Liu, D., & Li, J. (2020). Tocilizumab treatment in COVID‐19: a single center experience. Journal of medical virology, 92(7), 814-818.
  208. Cure, E., & Cure, M. C. (2020). Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 405-406.
  209. Cámara, M., Sánchez-Mata, M. C., Fernández-Ruiz, V., Cámara, R. M., Cebadera, E., & Domínguez, L. (2021). A review of the role of micronutrients and bioactive compounds on immune system supporting to fight against the COVID-19 disease. Foods, 10(5), 1088.
  210. Morioka, S.; Tsuzuki, S.; Suzuki, M.; Terada, M.; Akashi, M.; Osanai, Y.; Kuge, C.; Sanada, M.; Tanaka, K.; Maruki, T.; et al. Post COVID-19 condition of the Omicron variant of SARS-CoV-2. medRxiv 2022, in press.
  211. Yang F, Zhang Y, Tariq A, Jiang X, Ahmed Z, Zhihao Z et al (2020) Food as medicine: a possible preventive measure against coronavirus disease (COVID‐19). Phytother Res 34(12):3124–3136.
  212. Alkhatib A (2020) Antiviral functional foods and exercise lifestyle prevention of coronavirus. Nutrients 12(9):2633.
  213. Ghosh, D. (2021). Role of food or food component in brain health. In Nutraceuticals in brain health and beyond (pp. 3–13). Elsevier.
  214. Dai, H.; Han, J.; Lichtfouse, E. (2021) Smarter cures to combat COVID-19 and future pathogens: A review. Environ. Chem. Lett. 19, 2759–2771.
  215. Beran, A.; Mhanna, M.; Srour, O.; Ayesh, H.; Stewart, J.M.; Hjouj, M.; Khokher, W.; Mhanna, A.S.; Ghazaleh, D.; Khader, Y.; et al. (2022) Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis. Clin. Nutr. ESPEN, 48, 167–177.
  216. Dos Santos, O.V.; Langley, A.C.D.C.P.; de Lima, A.J.M.; Moraes, V.S.V.; Soares, S.D.; Teixeira-Costa, B.(2022) Nutraceutical potential of Amazonian oilseeds in modulating the immune system against COVID-19–A narrative review. J. Funct. Foods 94, 105123.
  217. Infusino, F.; Marazzato, M.; Mancone, M.; Fedele, F.; Mastroianni, C.M.; Severino, P.; Ceccarelli, G.; Santinelli, L.; Cavarretta, E.; Marullo, A.G.M.; et al. (2020) Diet supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection: A scoping review. Nutrients. 12, 1718.
  218. Chourasia Rounak, Padhi Srichandan, Chiring Phukon Loreni, Abedin Md Minhajul, Singh Sudhir P., Rai Amit Kumar. (2020). A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein. Frontiers in Molecular Biosciences. 7
  219. Traber MG, Stevens JF. (2011) Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 51:1000–13. doi: 10.1016/j.freeradbiomed.2011.05.017.
  220. FrattaPasini, A. M., Stranieri, C., Cominacini, L., &Mozzini, C. (2021). Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications. Antioxidants (Basel, Switzerland), 10(2), 272. https://doi.org/10.3390/antiox10020272
  221. Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. (1994) The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res. 64:212–9.
  222. Wimalawansa SJ. (2019) Vitamin D deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Biology. 8:30. doi: 10.3390/biology8020030.
  223. Ginde AA, Blatchford P, Breese K, Zarrabi L, Linnebur SA, Wallace JI, et al. (2017) High-dose monthly vitamin D for prevention of acute respiratory infection in older long-term care residents: a randomized clinical trial. J Am Geriatr Soc. 65:496–503. doi: 10.1111/jgs.14679.
  224. Manzi, P.; Di Costanzo, M.G.; Ritota, M. (2021) Content and Nutritional Evaluation of Zinc in PDO and Traditional Italian Cheeses. Molecules. 26, 6300.
  225. Corrao, S.; Mallaci Bocchio, R.; Lo Monaco, M.; Natoli, G.; Cavezzi, A.; Troiani, E.; Argano, C. (2021) Does evidence exist to blunt inflammatory response by nutraceutical supplementation during COVID-19 pandemic? an overview of systematic reviews of vitamin D, vitamin C, melatonin, and zinc. Nutrients. 13, 1261.
  226. Mohammad Bagher Majnooni, Sajad Fakhri, Gholamreza Bahrami, Maryam Naseri, Mohammad Hosein Farzaei, Javier Echeverría (2021) Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms, Evidence-Based Complementary and Alternative Medicine, vol. Article ID 6632623, 21 pages, 2021.
  227. Tabari, M.A.K.; Iranpanah, A.; Bahramsoltani, R.; Rahimi, R. (2021) Flavonoids as promising antiviral agents against SARS-CoV-2 infection: A mechanistic review. Molecules . 26, 3900.
  228. Liskova, A.; Samec, M.; Koklesova, L.; Samuel, S.M.; Zhai, K.; Al-Ishaq, R.K.; Abotaleb, M.; Nosal, V.; Kajo, K.; Ashrafizadeh, M. (2021) Flavonoids against the SARS-CoV-2 induced inflammatory storm. Biomed. Pharmacother. 138, 111430.

This entry is adapted from the peer-reviewed paper 10.3390/covid3040037

This entry is offline, you can click here to edit this entry!
Video Production Service