Several comorbidities have been shown to be associated with coronavirus disease 2019 (COVID-19) related severity and mortality. However, considerable variation in the prevalence estimates of comorbidities and their effects on COVID-19 morbidity and mortality have been observed in prior studies. This systematic review and meta-analysis aimed to determine geographical, age, and gender related differences in the prevalence of comorbidities and associated severity and mortality rates among COVID-19 patients. We conducted a search using PubMed, Scopus, and EMBASE to include all COVID-19 studies published between January 1st, 2020 to July 24th, 2020 reporting comorbidities with severity or mortality. We included studies reporting the confirmed diagnosis of COVID-19 on human patients that also provided information on comorbidities or disease outcomes. We used DerSimonian and Laird random effects method for calculating estimates. Of 120 studies with 125,446 patients, the most prevalent comorbidity was hypertension (32%), obesity (25%), diabetes (18%), and cardiovascular disease (16%) while chronic kidney or other renal diseases (51%, 44%), cerebrovascular accident (43%, 44%), and cardiovascular disease (44%, 40%) patients had more COVID-19 severity and mortality respectively. Considerable variation in the prevalence of comorbidities and associated disease severity and mortality in different geographic regions was observed. The highest mortality was observed in studies with Latin American and European patients with any medical condition, mostly older adults (≥ 65 years), and predominantly male patients. Although the US studies observed the highest prevalence of comorbidities in COVID-19 patients, the severity of COVID-19 among each comorbid condition was highest in Asian studies whereas the mortality was highest in the European and Latin American countries. Risk stratification and effective control strategies for the COVID-19 should be done according to comorbidities, age, and gender differences specific to geographical location.

Summary In the oceans, toxic secondary metabolites often protect otherwise poorly defended, soft-bodied invertebrates such as shell-less mollusks from predation. The origins of these metabolites are largely unknown, but many of them are thought to be made by symbiotic bacteria. In contrast, mollusks with thick shells and toxic venoms are thought to lack these secondary metabolites due to reduced defensive needs. Here, we show that heavily defended cone snails also occasionally contain abundant secondary metabolites, γ-pyrones known as nocapyrones, and that these pyrones are synthesized by symbiotic bacteria. This study shows that symbiotic bacteria can produce metabolites isolated from gastropod mollusks. The symbiotic bacteria, Nocardiopsis alba CR167, are closely related to potentially widespread actinomycetes that we propose to be casual symbionts of invertebrates on land and in the sea. The natural roles of nocapyrones are not known, but they are active in neurological assays at low micromolar levels, revealing that mollusks with external shells are an overlooked source of secondary metabolite diversity.

Complex polyketides are typically associated with microbial metabolism. Here, we report that animals also make complex, microbe-like polyketides. We show there is a widespread branch of fatty acid synthase-(FAS)-like polyketide synthase (PKS) proteins, which sacoglossan animals use to synthesize complex products. The purified sacogolassan protein EcPKS1 uses only methylmalonyl-CoA as a substrate, otherwise unknown in animal lipid metabolism. Sacoglossans are sea slugs, some of which eat algae, digesting the cells but maintaining functional chloroplasts. Here, we provide evidence that polyketides support this unusual photosynthetic partnership. The FAS-like PKS family represents an uncharacterized branch of polyketide and fatty acid metabolism, encoding a large diversity of biomedically relevant animal enzymes and chemicals awaiting discovery. The biochemical characterization of an intact animal polyketide biosynthetic enzyme opens the door to understanding the immense untapped metabolic potential of metazoans.

Diversity-generating metabolism leads to the evolution of many different chemicals in living organisms. Here, by examining a marine symbiosis, we provide a precise evolutionary model of how nature generates a family of novel chemicals, the cyanobactins. We show that tunicates and their symbiotic Prochloron cyanobacteria share congruent phylogenies, indicating that Prochloron phylogeny is related to host phylogeny and not to external habitat or geography. We observe that Prochloron exchanges discrete functional genetic modules for cyanobactin secondary metabolite biosynthesis in an otherwise conserved genetic background. The module exchange leads to gain or loss of discrete chemical functional groups. Because the underlying enzymes exhibit broad substrate tolerance, discrete exchange of substrates and enzymes between Prochloron strains leads to the rapid generation of chemical novelty. These results have implications in choosing biochemical pathways and enzymes for engineered or combinatorial biosynthesis. IMPORTANCEWhile most biosynthetic pathways lead to one or a few products, a subset of pathways are diversity generating and are capable of producing thousands to millions of derivatives. This property is highly useful in biotechnology since it enables biochemical or synthetic biological methods to create desired chemicals. A fundamental question has been how nature itself creates this chemical diversity. Here, by examining the symbiosis between coral reef animals and bacteria, we describe the genetic basis of chemical variation with unprecedented precision. New compounds from the cyanobactin family are created by either varying the substrate or importing needed enzymatic functions from other organisms or via both mechanisms. This natural process matches successful laboratory strategies to engineer the biosynthesis of new chemicals and teaches a new strategy to direct biosynthesis. S econdary metabolites are specialized molecules that are often directed outward at other organisms (1, 2). For example, under the sea, soft-bodied animals defend themselves using a diverse array of specialized chemicals, which are required for their survival (3, 4). Symbiotic bacteria, and not the host animal, synthesize many secondary metabolites (5), providing a link between symbiosis, chemistry, the survival of the animal and bacterial associates, and effects on predators and other organisms on coral reefs (6-8). The chemicals underlying these interactions are structurally diverse, comprising families of related compounds that are useful in drug discovery. Slight changes to chemical structure can drastically alter function, yet many marine natural products families are extremely diverse. Compounds such as marine animal defensive chemicals are critical to interactions between organisms (3) so that structural changes have consequences that potentially ripple through the environment. An open question has been, given these many constraints, how can chemical diversity arise?The evolution of novel chemistry likely relies in part...