Transmission, and the Immune System Nourishment
8.7 The Scenario of How the Lungs Come Down
8.7 The Scenario of How
posed dominantly of lymphocytes is the immune feature of both lungs. Consistently, peripheral blood demonstrated that CD4+ and CD8+ T cells, though generally decreased in numbers, become hyperactive. The other immunological character- istics of the disease include induction of T helper (Th) 17 cell development (represented with increased levels of inflammatory C-C chemokine receptor 6 (CCR6)) and enhancement of effectiv- ity of CD8+ T cells (indicated with increased fre- quency of T cells expressing cytotoxic granules).
There is also a pathological report of two cases with lung cancer who died of 2019-nCoV infection (Tian et al. 2020). We have to overlook this report because the impact the preexisting lung disease can have on pathological findings is pervasive.
8.7.3 Macrophage Population Properties in COVID-19 8.7.3.1 Blood Monocytes Are Larger
and More Complex in Patients with COVID-19
Using flow cytometry, the study (Zhang et al.
2020a) remarked a foreword scatter (FSC)-high population of atypical, large, vacuolated mono- cytes in the peripheral blood from patients with COVID-19 (n = 28). These cells included an expansion of monocytes, M1 macrophages, and M2 macrophages, because of the expression of surface markers related to monocytes, CD14 and CD16, and also a variety of markers including CD11b, CD68, CD80, CD163, and CD206 that define M1 and M2 macrophages. Besides, they could produce cytokines that are expressed by M1 (IL-6 and TNFα) and M2 macrophages (IL- 10). The COVID-19-related monocyte popu- lation contained a similar number of classical monocytes but did include higher numbers of intermediate and nonclassical monocytes.
Neither controls without COVID-19 nor patients with other infectious diseases, including HIV, tuberculosis, malaria, H1N1, and HTNV, exhib- ited such an FSC-high population of monocytes with multiple phenotypes.
8.7.3.2 Blood Monocytes Correlate with the Severity and Criticality of COVID-19
Patients who required admission to ICU pos- sessed a higher proportion of FSC-high mono- cytes than of FSC-low monocytes (Zhang et al.
2020a). Besides, the increased percentage of the FSC-low population of monocytes corresponded to discharge from the hospital.
8.7.3.3 Blood Monocytes Express the Lower Amount of ACE2 in Patients with COVID-19
ACE2 is present on different human monocyte cell lines (THP-1 and U939) and murine macro- phage cell (RAW264.7) lines (Zhang et al.
2020a). Patients with COVID-19 displayed lower levels of ACE2 on monocytes/macrophages than controls without COVID-19.
8.7.3.4 BALF Macrophages Are Different Among Patients with Severe and Mild COVID-19 The study (Liao et al. 2020) compared the BALF- derived specimens of eight people who had never been diagnosed with COVID-19 with that of those who had bilateral pneumonia and suffered from mild (N = 3 and age range 35–37 years) or severe COVID-19 (N = 3 and age range 62–66 years). Generally, it showed that different immune cells form 36 different cell clusters in the BALF. Precisely, the propor- tions of T cells and natural killer (NK) cells in patients with mild COVID-19 exceed those of patients with severe COVID-19, which in turn are higher than those of control subjects (Figs. 8.9 and 8.10). Also, the BALF in patients with severe COVID-19 would harbor a macro- phage population that is widely different from that in patients with mild COVID- 19 and con- trol subjects in both the amount and cellular phenotype. The severe COVID-19 BALF includes a higher number of macrophages char- acterized by two predominant cell types: mono- cyte-derived macrophages expressing Ficolin 1 (FCN1) and pro-fibrotic macrophages repre- senting secreted phosphoprotein 1 (SPP1) (Fig. 8.11).
8.7.3.5 SARS-CoV-2-Positive Macrophages Are Present in the Lung and Other Organs The study (Munster et al. 2020) of eight adult rhesus macaques has shown that inoculation with SARS-CoV-2 could cause irregular breathing patterns, weight loss, and fever.
Animals displayed pulmonary infiltrates in the lower lobes on one dpi, which progressed to the caudal lobes by three dpi. Also, they showed increased levels of cytokines, includ- ing IL-6, IL-10, IL-1RA, IL-15, MCP1, and MIP1B and high viral loads in the BALF. Necropsy confirmed interstitial pneu- monia characterized by gross lung lesions, thickening of the alveolar septa, edema fluid, fibrin, hyaline membrane formation, type II pneumocyte hyperplasia, alveoli with macro- phages and neutrophils, and perivascular infil- tration of lymphocytes. There were alveolar macrophages and type II pneumocyte positive for the SARS-CoV-2 antigen. Interestingly, antigen-positive macrophages were present in
tissues other than in those the respiratory sys- tem, including the mediastinal lymph nodes and the intestinal tract.
8.7.4 Anti-COVID-19 Macrophages:
Anti-inflammatory Macrophages that Induce Tolerance to Coronaviruses Resembling the Novel One in Bats
SARS-CoV is a bat-loving microparasite; bats serve as a natural reservoir for SARS-CoV (Li et al. 2005). Bat macrophages do not differ from mice macrophages in the amount of production of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IFNβ. However, bat macrophages act differently in terms of higher levels of the anti- inflammatory cytokine, IL-10, they can produce (Kacprzyk et al. 2017). The production of IL-10 is an effort to balance the heavyweight of pro- inflammatory cytokines. The mainte- nance of this balance might have determined
Fig. 8.9 The distribution of discrete cell types in the bronchoalveolar lavage fluid (BALF): controls without COVID- 19, patients with mild COVID-19, and patients with severe COVID-19
Fig. 8.10 The distribution of natural killer (NK) and T-cell clusters in the bronchoalveolar lavage fluid: controls with- out COVID-19, patients with mild COVID-19, and patients with severe COVID-19
that the tolerance to some deadly viral infec- tions is present in bats while it is absent in other mammals.
8.7.5 Pro-COVID-19 Macrophages:
ACE2-Hyperactivated Macrophages
As real-time world statistics disseminate it, the COVID-19 infectivity largely depends on the ini- tial host condition with a case fatality rate of 0.9% in patients without comorbid conditions compared with a range of 7.6% to 13.2% in patients with a comorbid condition. Among patients with different comorbid conditions, patients with preexisting cardiovascular disease and hypertension have the highest mortality rate.
COVID-19 infectivity depends on its receptor, i.e., ACE2 receptor. Monocyte-derived macro- phages in patients with hypertension and prehy- pertension exhibit higher ACE2 activity compared with individuals with normal blood pressure (Keidar et al. 2007).
8.8 Macrophage-Mediate Cell